The Chronicle of Skin & Allergy - April/May 2022

IL inhibitors

P RACTICAL T HERAPEUTICS and C LINICAL N EWS from the W ORLD of D ERMATOLOGY

n

A PRIL /M AY 2022

Rosacea roundup

New IL inhibitors continue to improve patient response n Use expanding beyond psoriasis to prurigo nodularis, HS

by LOUISE GAGNON,

All rights reserved. Chronicle Information Resources Ltd. Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917

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S

◼ Canadian physicians discuss alternative Tx options for rosacea patients

see page 4

Clinical practice

Choosing a biologic for AD treatment

n Criteria to consider as the selection of approved systemics for AD grows

by JOHN EVANS, Senior Editor, The Chronicle

W

ith several systemic treatments approved in Canada for treating atopic dermatitis (AD), and more undergoing clinical trials, this is an encouraging time for clinicians and patients with AD. However, having a wider selection of medications can complicate the choice of a treatment approach, and points out the need for an organized process of comparing options and selecting the right one

for a patient.

This was part of Dr. Aaron Drucker’s message during his presentation at the virtual Toronto Psoriasis Seminar (ToPS) and Robert S. Lester Postgraduate Dermatology Dr. Aaron Seminar on Nov. Drucker 19, 2021.

More approvals on the way Dr. Drucker compared advancements in AD therapy to the rapid growth over the last 15 years in the

available medications for psoriasis, which he described as ‘exponential’.

“We are lucky to be working in this era, where we have so many amazing treatments that are available to us for psoriasis,” he said.

However, Dr. Drucker noted that the diversity of treatment options makes it “difficult to keep up with what is best for which patient and what exactly is the mechanism for each molecule and the generic names and the trade names. It has been so overwhelming, the speed which these have all come at us.”

pecific interleukin pathways have been identified in addressing numerous skin conditions such as plaque psoriasis, atopic dermatitis (AD), and IL inhibitors have emerged as effective agents to treat these conditions. IL inhibitors are also being examined for conditions that have had few or no biDr. Jaggi ologic options Rao available such as generalized pustular psoriasis, prurigo nodularis, and hidradenitis suppurativa (HS).

Psoriasis and generalized pustular psoriasis “Tildrakizumab is the newest anti-IL23 biologic agent to be approved [for psoriasis], and it gives physicians yet another tool to help patients with severe psoriasis to improve quickly, effectively, and safely,” said Dr. Jaggi Rao, a dermatologist in Edmonton and Clinical Professor of Medicine at the University of Alberta. “Tildrakizumab is delivered via a subcutaneous injection, and its unique

Please turn to AD page 8→

Pediatric health

Diagnosis, management Connect with The Chronicle on www.derm.city of pediatric lupus “Where Dermatology Lives” n Improved understanding of role of type I

interferon activity leads to new Tx approaches

by LOUISE GAGNON, Correspondent, The Chronicle

T

he epidemiology of lupus, the criteria for classifying lupus, and emerging therapies for the condition were topics addressed by Dr. Julie Barsalou at the annual pediatric dermatology update organized by the Centre Hospitalier Universitaire (CHU) St. Justine in Montreal.

“The average age at which Please turn to Lupus page 14→

n Share your experiences and observations with a worldwide community of practitioners and researchers.

Follow developments in skin health as they occur. Visit www.derm.city

Please turn to Anti-IL page 12→

Ask your AbbVie representative to show you the full picture

© AbbVie Corporation CA-SKZD-220012A – March 2022

abbvie.ca 1-888-703-3006

Vol. 28, No. 3

THE CHRONICLE of S K IN & ALLE R GY

April/May 2022 • 3

A Message from the Medical Editor

T O P of the M O N T H Choosing a biologic for atopic dermatitis treatment Dr. Aaron Drucker discusses new options for the treatment of AD including new biologics. He also highlights the importance of considering how a treatment can improve patients comorbidities. . . .1 Vender on Psoriasis: Lack of reactivation of latent tuberculosis in PsO patients treated with secukinumab Also, researchers investigated the two-year safety profile of bimekizumab in patients with moderate to severe plaque psoriasis and found that bimekizumab was well tolerated . . . . . . . . . . . . . . . . . . .10 Treatment update: Pediatric health Researchers have shown that patients under the age of 18 with psoriasis are at an increased risk of developing alopecia areata compared to adult patients . . . . . . . . .18 Chronicle Postgraduate Educational Supplement In this issue’s educational supplement, researchers conduct a metaanalysis to compare the clinical efficacy and adverse events of UVbased therapy to treat psoriasis. Researchers conclude that combination UV therapy is more effective than UV monotherapy . . . . . . . . . . . . . . . . . 29

I

Research

Herbal remedies investigated in the treatment of chronic pruritus From the News Resources of The Chronicle

While there is only limited evidence that herbal remedies have a clinical effect on chronic pruritus, it does appear that turmeric, peppermint oil and capsaicin and manual therapies such as massage may provide some improvement for these patients. That’s according to a new study published in the Journal of Cosmetic Dermatology.

The researchers noted that the basis for this study was the clinical observation that conventional pruritus therapies are not always successful in providing satisfactory relief for patients.

Lead author Mohammad Mahdi Parvisi, MD, PhD of the Molecular Dermatology Research Center of Shahid Faghihi Hospital in Shiraz, Iran and his colleagues reviewed clinical

trials published between 2000 and 2019 that included herbal and complementary medicine as treatments for pruritus. They identified 17 total studies, with 11 articles related to herbal remedies such as turmeric, peppermint oil and capsaicin, while six articles evaluated manual therapies such as aromatherapy, massage and acupuncture in the treatment of chronic pruritus.

Their analysis of these studies indicated that some herbal remedies such as curcumin, peppermint, mint, capsaicin, and sweet almond, and manual therapies such as massage could alleviate and improve chronic pruritus in these patients.

However, the effects of these interventions were not well-defined in the identified studies, and more research needs to be done.

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April/May 2022 • Vol. 28 No.3 Published eight times per year by the proprietor, Chronicle Information Resources Ltd., with offices at 555 Burnhamthorpe Road, Ste 306, Toronto, Ont. M9C 2Y3 Canada. Telephone: (416) 916-2476; Facs. (416) 3526199.

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“[Patients] can have skin disease, they can have joint disease, they can have nail disease. And then they can have psoriasis on special sites, such as the genital area, scalp, palms, and soles.”

Dr. Lyn Guenther, dermatologist and Professor, Western University (see page 16)

n this issue of THE CHRONICLE OF SKIN & ALLERGY, we offer our readers an update on many of the latest advances in dermatologic therapeutics for a wide range of disorders. The therapeutic landscape in dermatology continues to evolve and whether it might be considering the recommendation of omega-3 fatty acids as a supplement, the potential role of JAK-inhibitors in the treatment of lupus, or presenting data on new rosacea treatments (which include both a topical tetracycline as well as new oral tetracycline), it's all in this issue.

We also review advancements in eczema which includes Health Canada approval of a new biologic and a JAK-inhibitor. And for our psoriasis patients, we continue adding to the list of impressive therapeutic options.

Readers will be pleased to learn that many of the advances are available in our clinics today, while others we expect to be approved in the near future. These therapies will fulfill many of the unmet needs that we as clinicians and our patients encounter.

Please turn to Message page 14→

Medical Editor

Wayne Gulliver,

MD, FRCPC

John P. Arlette, MD, FRCPC Benjamin Barankin, MD, FRCPC Marc Bourcier, MD, FRCPC Eric Goldstein, MD, FRCPC Peter Hull, MD, FRCPC Richard Langley, MD, FRCPC Danielle Marcoux, MD, FRCPC R.A.W. Miller, MD, FRCPC

Editor, Cosmetic Dermatology MD, FRCPC

Sheldon V. Pollack,

H. Eileen Murray, MD, FRCPC Kim Papp, MD, FRCPC Yves Poulin, MD, FRCPC Melanie D. Pratt, MD, FRCPC Denis Sasseville, MD, FRCPC Jerry Tan, MD, FRCPC Ronald B. Vender, MD, FRCPC

Founding Editor Colin A. Ramsay, MD, FRCPC (1936-2003) Publisher Mitchell Shannon Editorial Director R. Allan Ryan Senior Editor John Evans Lead Coordinator, Journals Kylie Rebernik

Assistant Editor Jeremy Visser Communications Coordinator Katherine Brenders Client Engagment Cristela Tello Ruiz Manager,Operations Cathy Dusome Comptroller Rose Arciero

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4

• April/May 2022

THE CHRONICLE of SKIN & ALLERGY

Mor e options for the tr eatment of r osacea n Additional alternative treatments include energy-based therapies

by LOUISE GAGNON, Correspondent, The Chronicle

N

ovel topical agents, a novel systemic antibiotic treatment indicated for acne, and the use of energy-based devices are likely to be incorporated into the dermatologist’s toolbox for the management of rosacea, according to dermatologists surveyed by THE CHRONICLE OF SKIN & ALLERGY. These treatments are designed to address the various features of rosacea such as erythema, telangiectasia, papules and pustules, and ocular manifestations.

“One of the emerging topical agents is encapsulated benzoyl peroxide or E-BPO, and another is topical micronized minocycline in

suspension, noted Dr. Mark Lupin, a dermatologist in Victoria, director and founder of Cosmedica, and a clinical instructor in the Department of Dermatology & Skin Science at the University of British Columbia.

Dr. Mark “The 5% E-BPO Lupin is a new drug delivery system,” said Dr. Lupin. “It improves penetration of active ingredients while reducing irritation as does 1.5% topical minocycline Dr. Alia foam.”

Bosworth Both these therapies are available in the U.S. and are expected to be available in Canada in the future, noted Dr. Lupin.

Dr. Alia Bosworth, a community dermatologist working in Halifax and a lecturer at Dalhousie University, Division of Cutaneous Science and Dermatology, noted the choice of a 1.5% minocycline foam is one that is appealing to patients, as is encapsu-

Image from stock.adobe.com

Rosacea roundup

lated benzoyl peroxide.

“Patients like foam as the vehicle,” said Dr. Bosworth. “It [1.5% minocycline foam] would be a good option to try. Benzoyl peroxide has antimicrobial properties, but it can be Dr. Charles irritating for people Lynde with rosacea. Having it in an encapsulated form would make it more tolerable.”

Acne therapies may help rosacea The acne treatment Dr. Lisa isotretinoin, in a Kellett low-dose form, is also an option for rosacea, but clinicians have to be cautious about prescribing it in female patients of child-bearing age because of its potential teratogenic effects, said Dr. Charles Lynde, Associate Professor, Department of Medicine, University of Toronto.

“You certainly have to be careful Please turn to AK page 6→

In the treatment of moderate-to-severe plaque psoriasis in adult patients

Is now available

ILUMYA™ (tildrakizumab injection) is indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Pr

For more information: Please consult the Product Monograph at: https://sunpharma.com/wp-content/uploads/0056-ca-m131-enpm-non-annotated-level-III-change-importer.pdf for important information relating to contraindications, warnings, precautions, adverse reactions, interactions, dosing and conditions of clinical use. The Product Monograph is also available by calling our medical information department at: 1-844-924-0656.

Enrol your patients in the Sun Patient Support Program for ILUMYA™ (1-844-561-1259 or ilumya@bayshore.ca)–designed to help you and your patients throughout the treatment journey

Current ILUMYA™ Product Monograph, Sun Pharma Canada Inc. © 2021 Sun Pharma Canada Inc. All rights reserved.

ILUMYA™ is a trademark of Sun Pharma Global FZE. Used under license.

PM-CA-ILY-0019

6 • April/May 2022

THE CHRONICLE of SKIN & ALLERGY

Rosacea: Unmet need for more study in darker skin Continued from page 4 when treating a woman who is still able to become pregnant,” said Dr. Lynde.

A new antibiotic therapy for acne that is in the tetracycline family is sarecycline, now available in the U.S. but not yet available in Canada. It may represent an off-label option in the treatment of rosacea, according to Dr. Lynde. “One study has shown efficacy to treat rosacea,” said Dr. Lynde, noting the drug has a narrow spectrum of antibiotic activity.

In a 12-week pilot study involving 102 patients randomized to sarecycline or a multivitamin tablet, which served as a placebo, sarecycline was found to be safe, effective, and well-tolerated in the treatment of papulopustular rosacea.

Reductions in inflammatory lesion counts were significantly greater in patients randomized to sarecycline (J Drugs Dermatol 2021 Apr 1; 20(4):426-431).

Dermatologists are increasingly concerned about the judicious use of antimicrobials to limit the development of antimicrobial resistant organisms, making sarecycline an attractive treatment, added Dr. Bosworth.

“If you had a patient who was treated with doxycycline and didn’t have a response, and you are thinking about the development of bacterial resistance, then I think sarecycline might be a good option,” said Dr. Bosworth.

Various features of rosacea equally important Dermatologists are placing emphasis on the management of not only papulopustular rosacea, but other aspects of the condition, according to

Dr. Lynde.

“One of the things is that people are recognizing the treatment of facial erythema is as important as the papules and pustules,” said Dr. Lynde in an interview with THE CHRONICLE OF SKIN & ALLERGY. Rosacea has traditionally been regarded as a skin condition that primarily affects lighter skin but there is an unmet need for more investigation in darker skin. “It is much more common in type I and type II skin,” said Dr. Lynde. “That said, some of these diseases have been understudied in skin of colour.”

With respect to ocular rosacea, dermatologists may consider partnering with their ophthalmology colleagues to provide comprehensive care, noted Dr. Bosworth.

“In a patient with ocular rosacea, you might have to think about making sure that the patient is followed by an ophthalmologist,” said Dr. Bosworth. “You can think about using preservative-free, natural tear eye drops. Using systemic antibiotics would be another consideration if they have significant eye involvement.”

Ivermectin as a mainstay Dr. Lupin has been prescribing topical ivermectin as a go-to treatment for his patients with rosacea.

“It has become a mainstay in my practice,” he said.

Dr. Bosworth also finds significant benefit in using ivermectin and initiates it in combination with other agents.

“I usually use [ivermectin] in combination with systemic antibiotics and have had really beautiful results,” said Dr. Bosworth. “We have

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really started to adopt it in the last few years and have obtained very good results.”

Energy-based devices and other innovations For the telangiectasia that can be characteristic of rosacea, laser therapy is regarded as beneficial, but other energy-based modalities can treat the papulopustular aspect of the chronic condition.

“You can use photodynamic therapy in patients with inflammatory rosacea who have lots of papules,” said Dr. Lisa Kellett, a Toronto dermatologist. “You would do it for about three to six sessions followed by every month as needed.”

Dermatologists need to keep in mind that in skin of colour, there is a risk of post-inflammatory hyperpigmentation when energy-based treatment of rosacea is employed, according to Dr. Kellett. “Be mindful that they can be prone to hyperpigmentation,” she said. “If they do get hyperpigmentation, you have to treat it.”

To tackle the rhinophyma that can be characteristic of rosacea, Dr. Lupin noted he performs laser resurfacing with a carbon dioxide laser.

There is also a trend to using microdoses of botulinum toxin in patients with rosacea, noted Dr. Bosworth. “By injecting very little botulinum toxin superficially in the skin, it may help with vasoconstriction and reducing the redness,” she said.

Non-proprietary and brand names of therapies: encapsulated benzoyl peroxide 5% (not approved in Canada); topical micronized minocycline foam 1.5% (not approved in Canada); isotretinoin (Accutane, Roche; Epuris, Cipher); sarecycline (not approved in Canada); doxycycline modified release capsule, 40 mg (Apprilon, Galderma); ivermectin cream 1% (Rosiver, Galderma).

ALSO INDICATED FOR USE IN ACTIVE PSORIATIC ARTHRITIS (PsA)

UNCOVER TREMFYA

®

POWERFUL EFFICACY DEMONSTRATED in moderate-to-severe psoriasis

Improvements in the Dermatology Life Quality Index from baseline were observed in patients treated with TREMFYA® compared to placebo at Week 16.1

PASI 90

PASI 100

73% (241/329) of patients achieved PASI 90 at Week 16 with TREMFYA® vs. 3% with placebo (co-primary endpoint) and 50% with adalimumab (secondary endpoint) (TREMFYA® 100 mg at Weeks 0 and 4, then every 8 weeks [n=329]; placebo at Weeks 0, 4, and 12 [n=174]; adalimumab 80 mg at Week 0, 40 mg at Week 1, then 40 mg every two weeks [n=334]; p<0.001, NRI)1* 76% (47/62) of patients achieved PASI 90 at Week 16 with TREMFYA ONE-PRESS® vs. 0% (0/16) with placebo (co-primary endpoint, p<0.001)1,2†

50% (31/62) of patients achieved PASI 100 at Week 16 with TREMFYA ONE-PRESS® vs. 0% (0/16) with placebo (secondary endpoint, p<0.001)1,2†

Indications and clinical use: TREMFYA®/TREMFYA ONE-PRESS® (guselkumab injection) is indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

TREMFYA®/TREMFYA ONE-PRESS® is also indicated for the treatment of adult patients with active psoriatic arthritis. TREMFYA®/TREMFYA ONE-PRESS® can be used alone or in combination with a conventional disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate).

Relevant warnings and precautions: • Do not initiate treatment in patients with any clinically important active infections until the infection resolves or is adequately treated • Discontinue treatment if patient develops a serious infection or is not responding to standard therapy for infection • Evaluate patients for tuberculosis infection prior to therapy and monitor for active tuberculosis during and after treatment • Consider completion of all immunizations prior to treatment • Concurrent use with live vaccines is not recommended • Discontinue treatment in cases of serious hypersensitivity reactions, including anaphylaxis, urticaria and dyspnea, and institute appropriate therapy • Women of childbearing potential should use adequate contraception

The image depicted contains models and is being used for illustrative purposes only.

19 Green Belt Drive | Toronto, Ontario | M3C 1L9 | www.janssen.com/canada © 2022 Janssen Inc. | All trademarks used under license. | CP-280806E

• Use during pregnancy only if clearly needed • The benefits of breastfeeding should be considered along with the mother’s clinical needs • Effect on human fertility has not been evaluated • Safety and efficacy in pediatric patients have not been evaluated • Data in patients ≥65 years of age are limited For more information: Please consult the Product Monograph at www.janssen.com/canada/products for important information regarding adverse reactions, drug interactions, and dosing and administration that has not been discussed in this piece.

The Product Monograph is also available by calling 1-800-567-3331. * VOYAGE 1: Multicentre, randomized, double-blind, placebo- and active comparator-controlled phase 3 study in 837 adult patients with moderate-to-severe plaque psoriasis (body surface area [BSA] involvement ≥10%, PASI score ≥12, Investigator’s Global Assessment [IGA] ≥3) with or without psoriatic arthritis who were candidates for systemic therapy or phototherapy. Patients were randomized to receive subcutaneous injections of TREMFYA® 100 mg at Weeks 0 and 4, then every 8 weeks (n=329); adalimumab 80 mg at Week 0, 40 mg at Week 1, then 40 mg every 2 weeks (n=334); or placebo at Weeks 0, 4 and 12 (n=174). At Week 16, patients receiving placebo crossed over to TREMFYA® 100 mg at Weeks 16 and 20, then every 8 weeks. † ORION: Multicentre, phase 3, double-blind, placebo-controlled study to evaluate TREMFYA® administered with the patient-controlled One-Press injector in adults with moderate-to-severe plaque psoriasis (i.e., IGA score ≥3; PASI score ≥12; BSA involvement ≥10% for ≥6 months prior to screening). Patients were randomized 4:1 to either TREMFYA® 100 mg at Weeks 0, 4, and every 8 weeks thereafter, or placebo at Weeks 0, 4,and 12, with crossover to TREMFYA® 100 mg at Week 16. SC injections for both treatment arms done with One-Press device. Co-primary endpoints: Proportion of patients achieving IGA 0/1 and PASI 90 responses at Week 16.

PASI=Psoriasis Area Severity Index; NRI=non-responder imputation; IGA=Investigator’s Global Assessment; BSA=body surface area; SC=subcutaneous.

References: 1. TREMFYA®/TREMFYA ONE-PRESS® (guselkumab injection) Product Monograph. Janssen Inc. September 17, 2021. 2. Ferris LK, Ott E, Jiang J, et al. Efficacy and safety of guselkumab, administered with a novel patient-controlled injector (One-Press), for moderate-to-severe psoriasis: results from the phase 3 ORION study.

J Dermatolog Treat 2019; doi: 10.1080/09546634.2019.1587145.

8 • April/May 2022

THE CHRONICLE of SKIN & ALLERGY

AD: Considering comorbidities when prescribing Txs Continued from page 1 The situation with AD is headed in the same direction, said Dr. Drucker. He mentioned the Canadian approval of dupilumab for adults with moderate-to-severe AD in 2017 and its subsequent approvals for younger patients, as well as the approvals of upadacitinib and tralokinumab in late 2021.

“So even though it is early days and we are not even close to where psoriasis is in the atopic dermatitis world, I think we are on our way up in that curve,” Dr. Drucker said. “That’s amazing from a patient treatment point of view. And it gives us options as clinicians but also makes our job more difficult. We have more [medications] that we need to know about, and more that we need to explain to patients as they decide what treatment is right for them.”

The task of comparing the different AD medication options is complicated in that it is difficult to evaluate the medications against one another just by reading trial abstracts, Dr. Drucker noted.

He said that many dermatologists are comfortable comparing psoriasis medications based on PASI (Psoriasis Area and Severity Index) numbers. “But in eczema, because placebo responses are so heterogeneous, varying so widely from trial to trial, we cannot do the same thing,” he said.

Dr. Drucker said that a clinician cannot simply rely on interpreting trials by comparing the number of patients in a trial who achieve EASI (Eczema Area and Severity Index) 75 or EASI 90 on a medication when placebo responses seen in trials have varied between 9% and 36%.

Meta-analysis can help determine benefits, drawbacks One way to work through these challenges and understanding the differences between medication options, where direct head-to-head comparison studies are impractical, is network meta-analysis, Dr. Drucker noted.

Dr. Drucker and a research group of his colleagues have been conducting a meta-analysis of trials of systemic medications for AD. The group published findings from a review of 39 studies in early 2020 (JAMA Dermatology April 22, 2020;156(6):659-667) but have been continuing to keep the review up to date as a living document, he said.

Information about the group’s analysis is

available at eczematherapies.com.

“Two years later there have been 21 new randomized control trials added,” said Dr. Drucker.

“What we are able to do [with the network metaanalysis] is get an idea of how these different treatments compare with each other using up to date data.”

Dr. Drucker presented some additional data, unpublished at the time of the seminar. At the time of writing that data has been published online in JAMA Dermatology (March 16, 2022).

“We can see from these trials that we have a bit of a hierarchy of how these treatments perform in terms of their effectiveness,” he said.

“These treatments in truth are not all that far apart [in terms of efficacy].” He noted that upadacitinib and abrocitinib appear to be slightly more effective than dupilumab in terms of EASI, and dupilumab seems to be more effective than tralokinumab and baricitinib.

“But again, at least in our network meta-analysis, the differences are all within this minimal clinically important difference range. There is not a huge difference between the different medications,” he said.

Factors to consider when prescribing With the differences in efficacy between these agents being relatively small, Dr. Drucker said the question becomes: “how am I going to choose between these different medications in clinical practice?”

Prior to the most recent approvals of biologic medications, he said, a dermatologist would typically try to prescribe their moderate-to-severe AD patients dupilumab. If that was not an option due to insurance coverage or another reason, then the choice would be between methotrexate, cyclosporine, phototherapy, or the other traditional options.

“Now we are going to have more targeted therapeutics with really good efficacy without some of the side effects that we worry about with those older, conventional therapeutics, what are we going to do?”

With these medications having similar efficacy, other factors such as safety may guide the dermatologist’s decision, Dr. Drucker said.

He noted that Janus kinase (JAK) inhibitors have an association with important adverse events, with some having black box warnings regarding heart-related adverse events, cancer,

blood clots, and death. Dr. Drucker also noted that there is an increased risk of some types of infections with most JAK inhibitors.

However, these warnings were developed from studies in arthritis patients who are often in poorer health than the AD patients being treated with these medications.

“So, while we cannot ignore these warnings, we also have to think about them and how they apply to our individual patients,” he said.

Dr. Drucker said dermatologists should give extra consideration to older adults before prescribing JAK inhibitors for AD. This population not only has more comorbidities and higher overall frailty but they are often also prescribed multiple pharmaceuticals. Because of changes in drug metabolism associated with age, and the elevated risk of hospitalization due to adverse events that are associated with polypharmacy, JAK inhibitors may not be the best choice for these patients, he said.

Regarding infection risk, Dr. Drucker noted that there are some minor signals in the literature that infection risk may be increased with upadacitinib and abrocitinib, but there are very low numbers of these infections in clinical trials. “I do not think there is enough data yet to firmly conclude that this is a major issue in our atopic dermatitis population.”

Another important consideration when choosing medications is whether a given medication may also help improve a comorbid condition the patient may have, Dr. Drucker said. He noted that JAK inhibitors are being used across a wide range of inflammatory conditions, with evidence in the literature for treating alopecia areata, and approvals for other inflammatory conditions such as ulcerative colitis and rheumatoid arthritis.

“If we have a patient with those comorbidities, and we can improve two different elements of a patient’s medical profile, then that is a great thing to do and might push us in one direction or another [in terms of medication choice],” he said.

Non-proprietary and brand names of therapies: dupilumab (Dupixent, Sanofi, Regeneron); upadacitinib (Rinvoq, AbbVie); tralokinumab (Adtralza, LEO Pharma); baricitinib (not approved in Canada for this indication); abrocitinib (not approved in Canada).

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Vender on Psoriasis Ronald B. Vender, MD, FRCPC comments on recent findings and developments, and answers clinicians’ questions

Bimekizumab: Pooled results from Phase 2 and Phase 3 randomized clinical trials To evaluate the two-year safety profile of bimekizumab in patients with moderate to severe plaque psoriasis, researchers analyzed pooled results from four Phase 2 and four Phase 3 randomized clinical trials in patients who received at least one dose of bimekizumab (JAMA Dermatol doi:10.1001/jamadermatol.2022.1185 published online May 11, 2022).

A total of 1,789 patients (1,252 [70.0%] men; mean [SD] age, 45.2 [13.5] years) who had been treated with one or more doses of bimekizumab across the phase 2/3 trials were included. Total bimekizumab exposure was 3,109.7 person-years. Treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation were reported using exposure adjusted incidence rates (EAIRs) per 100 person-years.

According to the investigators, TEAEs occurred at an EAIR of 202.4 per 100 person-years and did not increase with longer duration of bimekizumab exposure. The three most frequently reported TEAEs were nasopharyngitis (19.1 per 100 person-years; 95%CI, 17.4-20.9 per 100 person-years), oral candidiasis (12.6 per 100 person-years; 95%CI, 11.3-14.0 per 100 person-years), and upper respiratory tract infection (8.9 per 100 person-years; 95%CI, 7.8-10.1 per 100 person-years). Most oral candidiasis events were considered mild or moderate; three events led to discontinuation. The EAIRs of inflammatory bowel disease (0.1 per 100 personyears; 95%CI, 0.0-0.3 per 100 person-years), adjudicated suicidal ideation and behaviour (0.0 per 100 personyears; 95%CI, 0.0-0.2 per 100 person-years), and adjudicated major adverse cardiac events (0.5 per 100 person-years; 95% CI, 0.3-0.8 per 100 person-years) were low.

Bimekizumab was well tolerated aside from an increased incidence of mild to moderate oral candidiasis in this pooled data from eight randomized clinical trials. Compared to previous reports, no safety signals were observed. Longer duration of treatment with bimekizumab did not increase risk of AEs.

Lack of reactivation of latent tuberculosis in PsO patients treated with secukinumab

While some biologics for psoriasis, especially anti-tumour necrosis factor (TNF)-a therapies, may re-activate latent tuberculosis (TBC) infection, there is a low reported incidence of conversion to positive TBC status among patients with psoriasis treated with second-generation biologic therapies, particularly anti-interleukin (IL)-17 therapies such as secukinumab. However, in the clinical management of psoriasis, screening for tuberculosis infection is mandatory before starting biologic therapy.

According to protocols, psoriasis patients with a latent TBC infection with no evidence of clinically manifest active TB must undergo prophylactic treatment with isoniazid and/or rifampicin prior to the initiation of biologic therapy. This is also true for the newer biologics such as anti-interleukins (IL) 17 and 23, despite a low reported incidence of conversion to positive TBC status in patients treated with these therapies.

In this study published in the Journal of Dermatological Treatment (DOI:10.1080/09546634.2022.2062280, Bimekizumab is a new anti-IL-17A and F blocker approved for the treatment of mod- the safety profile of secukinumab in psoriasis patients with erate to severe PsO. This is the fourth biologic against IL-17. It was found in clinical latent TBC infection was analyzed by real-life data. The studies to be highly effective with superior PASI 90 responses with infrequent dosing data was collected using a retrospective chart review of of every four to eight weeks. This biologic has one safety concern that is higher patients with moderate-to severe psoriasis who showed than the other anti-IL17s: Candidiasis is likely the most common side effect to be positivity for TBC screening at baseline and then underseen with patients treated with bimekizumab. However, the incidence is very low. went secukinumab treatment for psoriasis at six Italian The majority of patients will NOT experience candidiasis. If it does occur, it is easily centres. Patients were treated with secukinumab 300 mg treatable without interruption of dosing and does not increase in frequency with at weeks 0/1/2/3/4, then every four weeks. A total of 59 continued dosing. The benefits still outweigh the minor risk presented by this safety patients were enrolled; 30.5% also had psoriatic arthritis concern. and other comorbidities were common. At baseline, the mean psoriasis duration was 14.5 years. Ten (17%) patients did not undergo prophylaxis before starting secukinumab, but isoniazid ± rifampicin or rifampicin alone prophylaxis was administered in 49/59 (83.1%) patients.

According to the results of this study published in Clinical and Experimental Dermatology (doi: Following a mean treatment duration of 84 weeks, the 10.1111/ced.15157), monitoring secukinumab trough concentrations during maintenance therapy can help to investigators noted there were no cases of TBC reactivaidentify patients who may benefit from treatment optimization since patients treated with secukinumab may tion and no unexpected safety signals. show varying clinical responses. For example, weight-based dosing may be required to prevent underexposure Psoriasis patients are fortunate to in patients with higher body mass index (BMI). have a wide variety of choices when In this multicentric, prospective study, the researchers worked to develop and validate a secukinumab imchoosing safe and effective biologics munoassay and potentially identify the therapeutic window in psoriasis patients. They collected secukinumab conto treat their moderate to severe discentrations in sera from 78 patients with psoriasis at multiple timepoints at trough during the maintenance phase of ease. The first studies of infliximab treatment. Also, disease severity of each patient was assessed through the Psoriasis Area and Severity Index (PASI) had the highest rates of latent TB conduring each visit to the hospital. versions when the exact process of After quantification, 121 serum samples were included for exposure-response analysis with the secukinumab screening patients BEFORE taking this immunoassay that was developed. They noted that based on a linear mixed-effects model, secukinumab trough biologic was not yet established. Derconcentrations decreased with increasing BMI. Based on receiver operating characteristic (ROC) analysis, they dematologists quickly learned that termined that a minimal effective secukinumab threshold of 39.1 mg/L in steady state could be deduced and was screening for active and latent TB is associated with a 92.7% probability of having an optimal clinical response (PASI≤2 or ΔPASI≥90%). important when starting anti-TNF bioThis is a very interesting study with this commonly used anti-IL-17 biologic for modlogics to prevent re-activation of this erate to severe psoriasis or psoriatic arthritis. Generally, the biomarker for skin psoendemic respiratory disease that can riasis is the clinical visual exam of rapid and effective reduction of redness, be quite high in certain countries and thickness and scaling as well as itch. In psoriasis patients we never measure therapopulations. However, the newer biopeutic levels of biologics and therefore this study is a new approach to potentially logics seem to still require testing for treating these patients with an adequate dose to either be able to titrate up dosing TB when it is unlikely to be necessary. or reduce the dosage if clinical response is achieved. This may be more important in This study shows that for secukpsoriatic arthritis however, and its use in dermatology is to be determined. inumab, this testing may not be required since there is no TB.

Dose optimization of secukinumab in chronic plaque psoriasis

We invite your comments and questions about this feature at www.derm.city. Dr. Ron Vender is a certified dermatologist with 29 years of clinical practice experience and over 75 clinical trials in psoriasis. He is founder and director of Venderm Innovations in Psoriasis, a center of excellence for Psoriasis offering a comprehensive management solution for individuals with psoriasis. www.psoriasis.vip

AVA NOW IN C ILAB AN LE AD A

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Indication and clinical use: Pr BIMZELX® (bimekizumab) is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.1 • Not authorized for use in pediatrics (< 18 years of age) • Limited data available for geriatrics (≥ 65 years of age) Relevant warnings and precautions: • Inflammatory bowel disease • Serious hypersensitivity reactions • Vaccinations • Infections, including tuberculosis • Pregnant or nursing women • Women of childbearing potential

For more information: Please consult the Product Monograph at https://ucbcanada.ca/sites/default/files/2022-03/bimekizumabpm-en-non-nds_14%20Feb%202022.pdf for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The Product Monograph is also available by calling 1-866-709-8444.

References: 1. BIMZELX Product Monograph. UCB Canada Inc. February 14, 2022. 2. Reich K, Papp KA, Blauvelt A, et al. Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial. Lancet. 2021;397(10273):487–498.

3. Gordon KB, Foley P, Krueger JG, et al. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY): a multicentre, doubleblind, placebo-controlled, randomised withdrawal phase 3 trial. Lancet.

2021;397(10273):475-486. 4. Warren RB, Blauvelt A, Bagel J, et al. Bimekizumab versus adalimumab in plaque psoriasis. N Engl J Med. 2021. doi: 10.1056/ NEJMoa2102388.

THE OPPORTUNITY TO

EXPECT EXCEPTIONAL Based on efficacy data vs placebo, adalimumab, and ustekinumab in pivotal phase III trials.2–4

BIMZELX, UCB, and the UCB logo are registered trademarks of the UCB Group of Companies. © 2022 UCB Canada Inc. All rights reserved.

12 • April/May 2022

THE CHRONICLE of SKIN & ALLERGY

Anti-IL: New therapies offer convenient dosing Continued from page 1 feature is that it requires the fewest number of injections compared to other anti-IL-23 agents.”

Dr. Rao noted six injections are needed in the first year, and four yearly injections thereafter.

Dr. Ben Barankin, a dermatologist, Medical Director and Founder of the Toronto Dermatology Centre in Toronto, agreed that the launch of tildrakizumab represents a new anti-IL player in psoriasis management that will offer convenient dos-

ing. “The frequency of injection is nice, as it is every three months,” he said. “This is the third IL-23 [for psoriasis] to be approved and join the family of risankizumab and guselkumab.”

A new development in the IL-23

Camp Liberté was created by a group of dermatologists dedicated to offering children with moderate to severe skin conditions an opportunity to enjoy a summer camp experience. With locations in eastern and western Canada, Camp Liberté hosts more than 40 children per summer at no cost to parents, thanks to the support of generous donors.

Our camps are fully equipped with volunteer dermatologists, residents and nurses to care for children with a wide range of skin conditions, including atopic dermatitis, epidermolysis bullosa, and alopecia areata.

HOW CAN YOU HELP?

A gift to Camp Liberté provides Canadian children with skin conditions an opportunity to grow in confidence and self-esteem through a multi-cultural outdoor camping experience in a fun, safe, bilingual, environment.

Donate Now! / Faites un don dès maintenant!

campliberte.ca

Le Camp Liberté a été créé par un groupe de dermatologues déterminés à offrir à des enfants qui ont des problèmes de peau variant de modérés à graves la possibilité de vivre l’expérience d’un camp d’été. Avec ses emplacements dans l’est et l’ouest du Canada, le Camp Liberté accueille plus de 40 enfants par été sans qu’il en coûte quoi que ce soit aux parents, grâce à l’appui de généreux donateurs.

Nos camps bénéficient des services complets de dermatologues, de médecins résidents et d’infirmières bénévoles qui s’occupent d’enfants aux prises avec un vaste éventail de problèmes de peau, y compris la dermatite atopique, l’épidermolyse bulleuse et la pelade.

COMMENT POUVEZ-VOUS AIDER?

Un don au Camp Liberté permet à des enfants canadiens qui ont des problèmes de peau d’accroître leur confiance en soi et leur estime de soi en vivant une expérience multiculturelle de camping en plein air offerte dans un environnement bilingue, sécuritaire et amusant.

”

inhibitor family is the recent approval of risankizumab for psoriatic arthritis, noted Dr. Barankin.

Another IL-17 inhibitor now approved for psoriasis is bimekizumab.

“Ongoing studies demonstrate amongst the fastest and most complete psoriasis clearance rates ever seen with it, more so than the currently available IL-17 inhibitors on the market,” said Dr. Rao. Dr. Catherine Zip, Clinical Associate Professor, Division of Dermatology, University of Calgary, agreed that bimekizumab, an IL-17A and IL17F inhibitor, will offer strong efficacy and its side effect of concern can be well managed.

“In head-to-head trials, it was shown to have superior efficacy to adalimumab, ustekinumab, and secukinumab,” said Dr. Zip. “Oral candidiasis can occur, but it’s mild-tomoderate in severity, rarely recurrent, and responsive to typical anti-candidal therapies. It [bimekizumab] is also being studied for treatment of psoriatic arthritis and hidradenitis suppurativa.”

Dr. Barankin described bimekPlease turn to Anti-IL page 26→

Chronicle Companies is pleased to support Camp Liberté with monetary and in­kind donations through Sandi’s Fund, estab­ lished to honour our late friend and colleague, Sandra Gail Leckie, RN. Sandi was a nurse, pharmaceutical industry execu­ tive and health educator who had a life long affinity for chil­ dren and children’s charities.

Chronicle Companies con­ tributes prots from the annual National Pharmaceutical Congress (www.pharmacongress.info) to Sandi’s Fund for Camp Liberté, and has partnered with Camp Liberté to provide communications assistance for this valuable philanthropic undertaking.

PERFORMANCE IS KEY TO CONSISTENT USE OF “FREE” LAUNDRY DETERGENTS 97% of dermatologists in Canada recommend the use of “free” detergents for sensitive skin1 Better cleaning drives compliance1 Many people with sensitive skin believe they must compromise on cleaning performance for mildness. In a recent survey of households with sensitive skin†1: • 39% are not satisfied with their “free” detergent’s cleaning performance • 60% are not satisfied with their “free” detergent and switch to a non-free detergent*

Superior cleaning performance helps patients follow recommendations1 A better performing detergent that is mild on skin may help patients follow their dermatologist’s recommendations of “free” detergents and decrease the likelihood of skin irritation.1 Tide Free & Gentle has been shown to provide significantly better cleaning performance vs. the next leading “free” detergent across a variety of testing methodologies.§

• 99% are more likely to use a “free” detergent that cleans better • 86% would be willing to pay more for a detergent if it cleaned better

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†vs. the next leading free detergent. Original image in B&W. Soil has been colourized to show contrast. P&G data on file.

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* When people switch from the next leading “free” laundry detergent † An internet survey of 3,175 people and 404 households in the US who are responsible for their laundry and laundry product purchasing conducted from late 2014 through early 2015. ‡ Tide Free & Gentle liquid detergent, Tide PODS Free & Gentle detergent, Tide + Downy Free & Gentle liquid detergent, Tide + Downy PODS Free & Gentle detergent, Downy Free & Gentle liquid fabric conditioner, Tide Free & Gentle Hygienic Clean Heavy Duty liquid detergent, and Tide PODS Free & Gentle Hygienic Clean Heavy Duty detergent have all earned the Eczema Society of Canada Seal of Acceptance. ® Registered Trademark of Eczema Society of Canada/Société canadienne de l’eczéma, used under license. § Earned National Psoriasis Foundation Seal of Recognition, excluding Bounce Free & Gentle dryer sheets.

Reference: 1. Johnson MB, Cella CE, Pessler A et al. Enhancing Patient Compliance for Usage of Laundry Detergents Free of Dyes and Perfumes: Potential Impact of Better Cleaning Performance. The National Society for Cutaneous Medicine 2020; 4(3):238-247. © P&G 2022

14 • April/May 2022

THE CHRONICLE of SKIN & ALLERGY

Lupus: Patients may not meet classification criteria Continued from page 1 [pediatric lupus] presents is 12, so it is quite rare before puberty,” Dr. Barsalou said, noting that about 20% of patients with lupus first present with the condition before the age of 18. She is a pediatric rheumatologist at the CHU St. Justine and Adjunct Clinical Professor at the University of Montreal.

Type I interferonopathies It has been recognized that interferon activity plays a role in lupus, but a greater understanding of this activity has emerged. “In the last 10 to 15 years, we have been able to understand more about interferon,” said Dr. Barsalou, noting the traditional focus has been on type I interferon activity.

An increase in knowledge is leading to a better understanding of the role of interferon activity in health and disease and the possibility of therapeutic initiatives aimed at limiting type I interferon signalling, she said.

Increased type I interferon activity has been reported in other complex rheumatic disorders including, but not limited to, systemic lupus erythematosus, dermatomyositis (DM), systemic sclerosis, rheumatoid arthritis and Sjögren’s syndrome.

There are clinical features observed across the type I interferonopathies, such as intracranial calcification and vasculitic skin lesions. In addition, neurological disease with lupus-like stigmata is a clue to type I interferonopathies.

STING-associated vasculopathy with onset in infancy (SAVI) is a type I interferonopathy that was first reported in 2014 and characterized as a pulmonary vascular syndrome that also has cutaneous features, noted Dr. Barsalou. It has been recently recognized that SAVI can feature significant lung involvement like interstitial lung disease.

Classification criteria for lupus Criteria from the European Alliance of Associations for Rheumatology and the American College of Rheumatology were developed for adult lupus but they have been validated for pediatric lupus, noted Dr. Barsalou. “The criteria have good specificity and good sensitivity,” she said.

Dr. Barsalou emphasized that while the classification criteria are helpful to use in a case of lupus, the

“Y

ou can’t exclude a diagnosis of lupus based on the fact that the patient does not meet the classification criteria” ⏤ Dr. Julie Barsalou

condition cannot be ruled out because a patient does not meet the classification criteria. “The classification criteria can guide you and help you to evaluate a patient,” she said, noting that there are no diagnostic criteria. “You can’t exclude a diagnosis of lupus based on the fact that the patient does not meet the classification criteria.”

Dr. Barsalou added that it is not necessary to exclude diagnoses in the absence of systemic inflammation.

Detecting monogenic lupus There are some clinical clues that can aid in the detection of monogenic lupus, including a family history of lupus, the development of lupus before puberty, recurrent infections, and a lack of response to standard treatments, pointed out Dr. Barsalou.

A family history, however, is not a necessary condition for making a diagnosis of monogenic lupus, said Dr. Barsalou. With respect to how monogenic lupus manifests in families, the phenotype can vary in the same family, she added.

Familial Chilblain Lupus, which belongs to the group of type I interferonopathies, presents with skin manifestations and acral ischemia, Dr. Barsalou noted. In terms of treatment, Janus kinase (JAK) inhibitors have been shown to produce a response in treating this type of lupus.

Specifically, research with baricitinib has demonstrated efficacy (JAMA Dermatol 2019 Mar 1; 155(3):342-346).

Optimal treatment of lupus Newer therapies have emerged to treat lupus, noted Dr. Barsalou.

Some of those include belimumab, voclosporin and anifrolumab, but traditional therapies like hydroxychloroquine remain a good option in the management of the disease, according to Dr. Barsalou.

Baracitinib has also shown to be effective in treating autoinflammatory diseases such as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) and SAVI (J Mol Med (Berl)

2016 Oct; 94(10):1111-1127).

In this double-blind, randomized, placebo-controlled, Phase II trial, oral baricitinib was examined for systemic lupus erythematosus.

The trial showed that baricitinib offered an acceptable safety profile and that there were significant improvements in the signs and symptoms of active systemic lupus erythematosus in patients not well controlled with standard therapy (Lancet 2018 Jul 21; 392(10143):222-231).

Other emerging therapies include complement inhibitors and sirolimus, noted Dr. Barsalou.

“Many treatments are in development and will be interesting for cutaneous involvement and other manifestations.”

Still another therapy under investigation that behaves similarly to a JAK inhibitor is a spleen tyrosine kinase inhibitor, which Dr. Barsalou noted may be an interesting option for the treatment of lupus with cutaneous involvement.

THERAPEUTIC INDEX AbbVie RINVOQ . . . . . . 35, 34 Skyrizi. . . . . . . . 2 Bausch Health Arazlo . . . . . . 25 Dermtek Pharma Dermburo . . . . . . 19 Pramox . . 15 ERFA HQ 4% Gel . . . 8

L’Oréal CeraVe . . . . . . . . . 21 Miravo Blexten. . . . . . . 27 P&G Fabric care. . . . . . .13 Pfizer Corporate. . . . . .9 Pierre Fabre Avène. . . . . . . 17

Galderma Aklief . . . . . . . . . 36 Cetaphil . . . . . 23

Sun Pharma Ilumya. . . . . . .5

Janssen Tremfya . . 7

UCB Bimzelx. . . . . . .11

Message from the Medical Editor Continued from page 3 I’m sure everyone who attends the annual meeting of the Canadian Dermatology Association in Quebec City from June 22 to 25th 2022 will see the data presented during the many scheduled scientific and educational sessions. For those of us who are unable to attend this year, The Chronicle can be your go-to-source for details regarding the many new and exciting advances in dermatology.

As always, THE CHRONICLE team invites and welcomes your comments on this issue, or any other topic in dermatology, at www.derm.city.

—Wayne P. Gulliver, MD, FRCPC, Medical Editor

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16 • April/May 2022

THE CHRONICLE of SKIN & ALLERGY

Patient car e

Simultaneous skin and nail psoriasis clearance

n A comparison of five head-to-head trials indicates that patients treated with ixekizumab

have more frequent simultaneous complete clearance than patients on other biologics

by JOHN EVANS, Senior Editor, The Chronicle

Nail involvement and QoL Dr. Guenther and her colleagues decided to investigate simultaneous clearance of skin and nails because of how common nail involvement is for patients with psoriatic disease and how it can impact their lives.

“Some 80 to 90 per cent of people [with psoriatic disease] will have nail involvement sometime during their disease,” Dr. Guenther said.

“Sometimes people say, well [nail involvement] is just cosmetic, people can feel embarrassed.

But sometimes we have also had patients where

Image from stock.adobe.com

C

ompared to four other systemic medications for psoriatic disease, patients treated with ixekizumab are more likely to achieve simultaneous clearance of their skin and nails.

This finding comes from research that examined data from five head-to-head trials and was published online ahead of print in Dermatology and Therapy (March 13, 2022).

With the help of advances in biologic therapies, dermatologists have been improving the rate that patients with psoriatic skin disease achieve complete clearance— PASI 100—said the paper’s senior author Dr. Lyn Guenther in an interview with THE CHRONICLE OF SKIN & ALLERGY. However, patients may have manifestations of psoriatic disease other than skin involvement, so clearing multiple disease manifestations Dr. Lyn Guenther would be preferable to clearing just the skin, she said. “[Patients] can have skin disease, they can have joint disease, they can have nail disease.

And then they can have psoriasis on special sites, such as the genital area, scalp, palms, and soles.

So, the optimal thing for patients would be if a dermatologist could clear all of these various areas.”

their nails are so thick they cannot do their buttons up, they cannot pick up small parts at work.

So just day-to-day functioning and functioning at work can be troublesome for people.”

Head-to-head study data assessed To evaluate the effectiveness of different systemic therapies in achieving simultaneous skin and nail clearance of psoriasis, Dr. Guenther and her colleagues used data from several clinical trials (IXORA-R, IXORA-S, UNCOVER-2, UNCOVER-3, and SPIRIT-H2H). These trials compared results from treatment with ixekizumab to etanercept, guselkumab, ustekinumab and adalimumab.

The SPIRIT-H2H trial compared ixekizumab

to adalimumab for the treatment of psoriatic arthritis, but there were patients in the cohort who had psoriatic skin and nail disease at baseline. Data from this subset of patients were used for the new analysis.

In the other four trials, ixekizumab was compared to another biologic for clearing skin psoriasis.

Patients from those trials who had nail involvement at baseline were included in this new study.

The investigators examined data on patients with moderate-to-severe psoriasis, with or without psoriatic arthritis, who also had nail psoriasis

Please turn to PsO page 20→

Research

Scar outcomes not improved by closer sutures in wound closure, new study indicates Closer 1 cm suture spacing when closing wounds does not result in better cosmetic outcomes than 2 cm spacing, new findings show.

Published online in the British Journal of Dermatology, the findings come from a randomized split-wound trial in 50 patients.

In the paper, the authors note that surgical reconstructions following Mohs micrographic surgery and standard surgical excisions are often closed with two layers of sutures: a deep subcuticular layer and a superficial cuticular layer. They note that some surgeons feel that placing many deep sutures will reduce tension on cuticular sutures. This reduced tension would then decrease the incidence of track marks and dehiscence and leading to better cosmetic outcomes. A competing view is that more subcuticular sutures raise the risk of a reaction to the sutures, patient anxiety, and poorer wound outcomes.

To test whether suture spacing had an impact on cosmetic outcomes, in each of the 50 patients

in the trial the researchers repaired half of the wound with sutures spaced 2 cm apart and the other half with sutures spaced 1 cm apart.

Two observers and the patients themselves evaluated the scar three months after the surgery using the Patient and Observer Scar Assessment Scale (POSAS). Evaluators and patients were both blinded as to which side received which treatment.

The researchers observed no significant difference at three months in the total mean POSAS score for observers for the sides that received 1 cm and 2cm interval subcuticular sutures. There was also no significant difference between the sides in the patient assessment.

"We found that 1 cm suture spacing was not significantly associated with improved overall cosmetic outcome compared with 2 cm suture spacing when evaluated by blinded observers or the patients themselves. Our results support the use of either interval," the authors write.

50

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Recent scars

Children

18 • April/May 2022

Pediatric update

THE CHRONICLE of SKIN & ALLERGY

Research

Research

Alopecia areata in youth

Depression and AD

n Psoriasis puts kids at higher risk for AA

n Risk of depressive symptoms in children

From the News Resources of The Chronicle

From the News Resources of The Chronicle

According to a new study, patients with psoriasis are at an increased risk of developing alopecia areata.

The authors conducted a meta-analysis that included a total of 27 studies with more than 120,000 psoriasis patients to investigate the link between psoriasis and alopecia areata.

The study was published in the Journal of Dermatology (May 5, 2022).

The analysis showed that the pooled prevalence of alopecia areata among psoriasis patients was 0.5%. The pooled prevalence of psoriasis among alopecia areata patients was 2.5%.

The investigators found that bidirectional association between psoriasis and alopecia areata was greater among those 18 years of age and younger than the adult group.

The authors recommended clinical examinations to determine the presence of comorbid alopecia areata in psoriasis patients and vice versa to improve individualized patient care.

A longitudinal cohort study has found that severe atopic dermatitis (AD) was associated with symptoms of depression and internalizing behaviours throughout childhood and adolescence. The investigators also found that the risk of internalizing symptoms was increased even for children with mild AD beginning early in childhood.

Published online in JAMA Dermatology (Sept. 1, 2021), the study used data on children followed from birth for a mean (SD) duration of 10.0 (2.9) years. A total of 11,181 children were included in the analysis.

The investigators found that although mild to moderate AD was not associated with symptoms of depression, it was associated with internalizing behaviours as early as four years of age. Severe AD was associated with both symptoms of depression and internalizing symptoms.

While children’s sleep quality mediated some of the association between AD and symptoms of depression, the association was not explained by differences in sleep duration, asthma or rhinitis, or levels of inflammatory markers including interleukin 6 and C-reactive protein.

Treatment Update DIFFERENT TYPES OF EMOLLIENTS EQUALLY EFFECTIVE FOR ECZEMA A recent head-to-head study comparing four types of emollients for childhood eczema found no difference in effectiveness between lotions, creams, gels, or ointments.

The authors of the paper, published in The Lancet Child and Adolescent Health (May 23, 2022) conclude that patients should be able to choose from a range of emollients so they can find one they are likely to use effectively.

A total of 550 children with eczema aged under 12 years were enrolled and randomized to use one of the four types of emollient as their primary moisturizer for 16 weeks.

Parents of the children in the study completed diaries about the child’s eczema for one year.

Researchers also interviewed some of the parents to gain a more in-depth understanding of how they applied the emollients and what the parents thought of them. The investigators found that when used alongside other eczema treatments there was no difference in effectiveness between the four types of emollient. Skin reactions such as itching were common with all moisturizer types.

Participants had low awareness of the different types of emollients, and their preferences were generally based on how the moisturizers looked and felt. Some participants liked how lotions quickly soaked in whereas others preferred the “barrier” provided by ointments.

NEW STUDY SHOWS ASSOCIATION OF AD WITH DELINQUENT BEHAVIOURS A recent meta-analysis has suggested a link between atopic dermatitis (AD) and delinquent behaviours in children and adolescents in the U.S. children born between 1998 and 2000 in 20 US cities.

The study was published in Archives of Dermatological Research (Jan. 10, 2022).

At age nine, children in the study were asked if they had performed any delinquent behaviour from a list that included destruction of property, theft, violence, substance abuse and other acts.

At age 15, adolescents were asked similar questions on delinquent behaviours such as fighting, vandalization, breaking and entering car theft and other acts.

The researchers found that a one year history of AD was significantly associated with being in the 75th percentile of mean deliniquent behaviour at nine years of age, but a one year history of AD at 15 years of age was not associated with this increase.

Children with persisting AD at multiple age groups also had significantly increased odds of being in the 75th percentile of mean delinquent behaviour at 15 years of age.

AD was significantly associated with damaging property, cheating on a test, fist fight involvement and school suspension.

CHARACTERISTICS OF LONGITUDINAL MELANONYCHIA REGRESSION IDENTIFIED A new study from Korea reports that the lesions associated with pediatric longitudinal melanonychia (LM) should be evaluated differently than the same condition in adults.

The retrospective study was published in the Journal of the American Academy of Dermatology (Apr. 5, 2022) and was designed to help identify the clinical features and natural course of pediatric LM and to determine some factors associated with prognosis. The study included a total of 703 lesions in 381 children. Single, narrow, and homogeneously pigmented LM were most frequently seen. They noted that most patients had a single lesion, and fingernails were involved twice as often as toenails (68.5% vs.

37.5%). More than 50% had nail-biting habits. Congenital LM was rare (1.8%).

According to the study results, within 3, 4.5, and 9.5 years after onset, approximately 3%, 5%, and 10% of LM lesions in these pediatric patients completely regressed. The researchers noted that single, leftsided, and homogeneously pigmented lesions were more likely to completely disappear. Pigmentation getting lighter over time was associated with complete regression, while a change in width was not.

PRE-PREGNANCY OBESITY MAY BE LINKED TO INCREASED RISK OF AD IN INFANTS, STUDY FINDS New research has suggested that intrauterine mechanisms of overweight women in pre-pregnancy may have increased risks of their infants having atopic dermatitis (AD).

According to the authors, previous studies have linked pre-pregnancy body mass index (BMI) and gestational weight gain to allergic disorders in offspring, such as AD and wheezing. However, associations were inconsistent and the authors aimed to include paternal BMI as a negative control exposure.

The study included 12,845 pregnant women who gave birth between 2012 and 2017, as well as data on 10,522 children from the Born in Guangzhou Cohort Study from the same years. It was published online in Pediatric Allergy and Immunology (Nov. 22, 2021).

Of the participants, 67.3% of the women had normal BMI, 22.5% were underweight and 10.2% were overweight or obese. Gestational weight gain was adequate in 46.3% of participants, inadequate in 26.3% and excessive in 27.4%.

As a continuous variable, the investigators concluded that pre-pregnancy BMI was not linked to risk of AD in infancy. .

The study did show that infants born to women who were overweight prior to their pregnancy had a higher risk than those born to women with normal weight prior to their pregnancy. There was no association found with paternal BMI.

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THE CHRONICLE of SKIN & ALLERGY

PsO: Clearance of skin, nails NB for patient DLQI Continued from page 16 at baseline. PASI 100 depicted complete skin clearance, and either Physician's Global Assessment of Fingernail Psoriasis (PGA-F, the IXORA-R trial) or Nail Psoriasis Severity Index (NAPSI, all other trials) depicted com-

plete nail clearance.

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achieved a high rate of simultaneous clearance in all the head-tohead trials at week 24—ranging from 28.6 to 45.9%. This clearance was well maintained up to week 52—ranging from 40.5% to 51.4% among the five studies. The investi-

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The conference provides education on treating patients across all six Fitzpatrick skin types, emphasizing care for Types IV-VI. The eighth annual Skin Spectrum Summit will be a hybrid event held on Saturday September 17, 2022

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gators also found numerically greater simultaneous clearance with ixekizumab compared to guselkumab at week 24 (p=0.079), but statistically significant greater simultaneous clearance compared to ustekinumab (p<0.001) and adalimumab (p=0.006) at week 24 and week 52 (p<0.001 and p=0.007, respectively).

Because nails grow slowly, seeing these degrees of nail clearance at week 24 is impressive, and physicians could likely expect greater rates of clearance over longer periods, Dr. Guenther said.

Importance of skin clearance These findings emphasize the importance of striving for complete skin clearance, as they show PASI 100 is frequently associated with improvement—even complete clearance—of nail psoriasis, said Dr. Guenther.

“I think the clearer we get people, the better their DLQI (Dermatology Life Quality Index). But now we have also shown that [patients with complete skin clearance] have much less chance of having nail disease,” she said.

“I think it is time to look not just at PASI 100 [as a way of evaluating treatment success], but also to look at other parameters, including nails.”

Dr. Guenther who is a member of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) said that while there are several tools for evaluating different aspects of psoriatic disease— PASI, NAPSI and the American College of Rheumatology’s minimal disease activity measure for psoriatic arthritis—there is no one measure for overall psoriatic disease activity.

For deciding on treatment goals, though, the evidence found by this study of the relationship between complete skin clearance and simultaneous complete clearance of nail psoriasis suggests that PASI 100 should remain a treatment target for patients with psoriatic skin disease, Dr. Guenther said.

Non-proprietary and brand names of therapies: ixekizumab (Taltz, Lilly); etanercept (Enbrel, Amgen); guselkumab (Tremfya, Janssen), ustekinumab (Stelara, Janssen); adalimumab (Humira, AbbVie).

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22 • April/May 2022

THE CHRONICLE of SKIN & ALLERGY

Skin health

Omega-3 fatty acids beneficial in dermatology

n Dietary supplementation can be a reasonable choice for improving acne, other skin conditions

by JOHN EVANS, Senior Editor, The Chronicle

A

literature review examining the potential value of omega-3 fatty acid (O3FA) supplementation to help manage dermatologic conditions has concluded that this supplementation is a reasonable option for individuals looking to improve skin conditions, particularly acne, through diet.

The findings were published online ahead of print in the Journal of Cutaneous Medicine and Surgery, (May 28, 2020).

In an interview with THE CHRONICLE OF SKIN & ALLERGY, the study’s senior author, Dr. Mariusz Sapijaszko, said that the idea for the study came about due to patient interest in extra, non-medical steps they could take to manage their condition.

“In my practice, talking with colleagues and patients, I found that patients often ask what they can do themselves to improve their conditions,” he said. Dr. Sapijaszko is the medical director of the Western Canada Dermatology Institute and Youthful Image Clinic, as well as a clinical professor at the University of Alberta Division of Dermatology in

Edmonton.

He said that much of the patients’ questions about self-management related to changes they might make to their diet, or supplements they could take, so he and his colDr. Mariusz leagues decided Sapijaszko to look into the existing dermatology-related literature on O3FAs. Dr. Sapijaszko said that O3FAs are known to have health benefits and can be readily obtained through dietary changes.

To evaluate the existing dermatologic literature on O3FAs, specifically, those relating to O3FA intake and skin health, Dr. Sapijaszko and his colleagues conducted a search using Ovid MEDLINE. They also performed a manual search of reference lists to identify any additional articles that warranted inclusion.

A total of 38 studies met the research team’s eligibility requirements. These reported benefits for O3FA supplementation in the treatment of a variety of skin conditions,

as well as some protective effects against certain sources of skin damage.

There was fairly clear evidence in the literature, Dr. Sapijaszko said, that O3FA from either diet or supplements was beneficial in the management of atopic dermatitis, psoriasis, acne and skin ulcers. He also noted there was evidence that O3FAs could be useful in cancer prevention through reducing photodamage, and that they also helped reduce the severity of side effects for patients taking isotretinoin.

Limitations of the studies noted Dr. Sapijaszko noted that one limitation is that most of the studies in the literature were prospective studies that looked at the benefits of prepared supplements rather than dietary intake of O3FAs. The studies that did look at intake of O3FA from food tended to be retrospective, and relied on patient recall of what they had eaten, with the known limitations on the reliability of that type of reporting, he said.

O3FAs worth recommending Overall, Dr. Sapijaszko said the study findings suggest it is worth

recommending O3FA supplementation to dermatology patients, for three reasons. “Number one, there is evidence of benefit. Number two, the side effect profile is good. And number three, the cost is low,” he said.

There was no specific evidence supporting adding O3FA-rich foods to one’s diet being superior or inferior to supplementation through tablets, capsules, or similar delivery, Dr. Sapijaszko said. However, he did say that as the supplement industry is not well regulated, patients should research any supplements they are considering taking.

In particular, he said they should be “cognizant of purity and potential contamination.”

The paper concludes that “O3FA is a reasonable supplement that may benefit patients wishing to improve inflammatory skin conditions through diet. Areas of particular clinical interest where supplementation may be valuable include O3FAs for systemic UV photoprotection, as well as adjuvant treatment for acne to reduce both inflammatory lesion count and the severity of mucocutaneous side effects associated with isotretinoin use.”

Skin Spectrum Summit

Cultural competence in skin of colour

n Education on cultural matters will help dermatology residents treat people, not diseases Physicians practicing anywhere in Canada should be comfortable diagnosing and counselling patients of all backgrounds and all skin types, said Dr. Bolu Ogunyemi during the 7th annual Skin Spectrum Summit on Nov. 6.

Dr. Ogunyemi is a dermatologist and the Assistant Dean of Social Accountability and a Dr. Bolu Clinical Assistant Professor of Ogunyemi Medicine in the Faculty of Medicine at Memorial University in St. John’s, Newfoundland & Labrador.

He stressed the importance of addressing the lack of diversity in undergraduate medical education.

“The undergraduate curriculum is a clear way to expose all future physicians to skin of colour dermatology and different cultural issues and how they reflect dermatology,” he said.

Canada's changing demographics make this education even more essential, he said.

Dr. Ogunyemi referred to a recent study from the University of Toronto (Journal of Cutaneous Medicine and Surgery, July 1, 2021; 25(4):409-417) that examined skin of colour representation in undergraduate dermatologic education materials and whether there was a link to diagnostic ability and confidence.

Findings from that study included: • In the first-year curriculum, 3.7% of images were of skin of colour • In the third year, 6.1% of images were of skin of colour • Students showed similar diagnostic accuracy when examining pictures of White skin or skin of colour • Students were less confident about their answers for skin of colour Dr. Ogunyemi also stressed the issue is not

just diagnostic accuracy.

“We treat people, not just diseases,” said Dr. Ogunyemi. “Culturally competent care is a lot more than having seen a lot of images of different dermatoses in skin of colour.” He said that true cultural competence includes meeting people where they are, understanding why a patient is seeking treatment, and considering demographic factors in disease presentation, care, and counselling.

There is a definite lack of representation of skin of colour in undergraduate medical education, which can make doctors less confident about diagnosing patients of colour and may ultimately affect diagnostic accuracy. To treat all patients anywhere in Canada, physicians need more exposure to skin of colour patients in training. But cultural competence also requires understanding the patient beyond just their dermatological issues.

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THE CHRONICLE of SKIN & ALLERGY

Te s t i n g p r o t o c o l s

Patch testing in atopic dermatitis patients

n New therapies may confound patch test results, according to a presentation at Derm Update

Image from stock.adobe.com

do not have any data to support that,” she said.

by LOUISE GAGNON, Correspondent, The Chronicle

P

atch testing atopic dermatitis patients for contact dermatitis will likely become more complex as these patients will increasingly be on systemic therapies, according to Dr. Gillian de Gannes.

Speaking at the fall Dermatology Update in November, Dr. de Gannes said, “We are going to see these atopic patients [on systemic therapies like dupilumab], and we are going to want to know if there is contact dermatitis present.” She is Director, Contact Dermatitis Clinic, University of British Columbia Department of Dermatology & Skin Science, Vancouver.

Recent research has highlighted that atopic patients can be patch tested while they are on dupilumab (J Am Acad Dermatol 2020; 82:132138). One study involving 48 patients showed only 10% of the patch test reactions were lost, meaning what tested positive before dupilumab was initiated was negative when patients were on dupilumab, Dr. de Gannes said.

“From the small amount of data that we have, dupilumab does not appear to affect patch testing results,” she added.

Dr. de Gannes explained the hypothesis has been that dupilumab will dampen the patch test reactions to some allergens, and that if a clinician is testing patients while they are on dupilumab, false negatives may be generated. The study results, however, did not support that hypothesis. “Most of the positive patch test reactions were the same [before and after initiation of dupilumab],” said Dr. de Gannes.

Asked if emerging systemic therapies that will better control atopic dermatitis will lead to a decrease in allergic contact dermatitis, Dr. de Gannes replied that it is conceivable. “Possibly with better skin barrier function, there may be a decrease in allergen exposure and allergic contact dermatitis.”

Patch testing when patients are on other systemics While dupilumab has been shown to largely not interfere with patch test reactions, other systemic therapies may, she noted.

“In general, there is not a lot of literature [on the topic],” said Dr. de Gannes. “There are not big, controlled studies looking at patch testing patients who are on systemic therapies.”

One study found that the intake of prednisone can confound the re-

sults of a patch test, leading Dr. de Gannes to avoid patch testing patients while they are taking prednisone unless it is a very low dose (Contact Dermatitis 2004; 50:298-303).

“At our clinic, we encourage no prednisone if possible or less than 20 mg daily,” said Dr. de Gannes.

Methotrexate does not appear to interfere with patch testing and the interpretation of results, but traditional systemic therapies such as cyclosporine, mycophenolate mofetil or azathioprine can confound an accurate evaluation of patch test results, Dr. de Gannes said.

“I interpret the result of [other conventional systemic therapies outside of methotrexate] with caution,” said Dr. de Gannes. “If it is a negative test, I sometimes say maybe in the future we will have to patch test again when the patient is not on these other medications.”

When asked if the systemic agent alitretinoin would interfere with determining the results of patch tests, Dr. de Gannes replied that her suspicion is that it does not, but noted the absence of clinical evidence to buttress her claim.

“I don’t believe that it has a strong influence on the immunology of having a positive patch test, but I

Where to test, testing in one visit, and delayed readings “You need to let patch testers know that testing to a standard series is not enough,” said Dr. de Gannes.

“We may have to go beyond and look for more [allergens].”

Where to patch test on the body can sometimes be a challenge, noted Dr. de Gannes. While the back is a typical patch testing site, clinicians may have to look for alternatives if a patient has active dermatitis on the back.

“It depends where the patient has clear skin,” said Dr. de Gannes.

“Recently I had to use the chest, the forearms and the thighs because the patient had dermatitis everywhere else. When patch testing, you want your patches to stick. If they won’t stick, then that’s a problem.”

Moreover, false-positive patch tests to many of the tested allergens can often occur when there is excited skin syndrome such as “angry back”, said Dr. de Gannes.

“It’s often when they [patients] have some sort of dermatitis,” she said. “We have to be really careful when we patch test our atopic dermatitis patients, ensuring that their skin is better controlled or else we will find this [hyper-irritability of the skin leading to false positives].”

Still, clinicians should aim to perform patch testing in one visit if possible, so patients do not have to endure patch testing at a subsequent visit, noted Dr. de Gannes.

It’s important that dermatologists inform their patients of any known contact allergens and to avoid those contact allergens, she said.

Another pearl for clinicians is that patch test readings need to be done beyond the day that the patches are taken off the skin, for some positive patch test reactions may not emerge the same day the patches are removed (on day 3), stressed Dr. de Gannes.

“If you are doing patch testing, you have to do delayed readings to pick up positive reactions,” said Dr. de Gannes. “In our clinic, in a recent review [of cases], at least one-third of patients did not show their contact allergy until we did their delayed reading (on day 8).”

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Clinical use: • Geriatrics (>65 years of age): The safety and efficacy of ARAZLO have not been established in this patient population.

• Patients 10 to <12 years of age should limit application of ARAZLO to the face.

Contraindications: • Hypersensitivity to retinoic compounds • Pregnant women or women who may become pregnant • Should not be used in the presence of seborrheic dermatitis Relevant warnings and precautions: • For external topical use only • Use of topical tazarotene may produce contact dermatitis

• Avoid concomitant use of medications and cosmetics that have a strong drying effect • Avoid application to eczematous or sunburned skin • Photosensitivity • Caution with coadministration of drugs known to be photosensitizers • Use adequate birth-control measures in women of childbearing potential • Discontinue treatment if patient becomes pregnant • Breastfeeding For more information: Please see the Product Monograph at https://bauschhealth.ca/wp-content/ uploads/2021/07/Arazlo-PM-E-2021-07-08.pdf for important information on adverse reactions, drug interactions and dosing not discussed in this piece.

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26 • April/May 2022

THE CHRONICLE of SKIN & ALLERGY

Anti-IL: Investigations in other conditions involving itch Continued from page 12 izumab as a distinctive IL-17 inhibitor because of how it works. “As an IL-17 inhibitor, it is unique because it binds to both A and F,” said Dr. Barankin. “With respect to safety and efficacy, it will be one of the best IL-17 inhibitors, but it presents a higher candidiasis risk.”

The enthusiasm around the expected availability of bimekizumab is shared by other dermatologists including Dr. Kerri Purdy, Division Head and Assistant Professor in the Division of Clinical Dermatology & Cutaneous Science, Department of Medicine, Dalhousie University, Halifax.

“I am most excited about bimekizumab coming out,” said Dr. Purdy.

“I am looking forward to having another option in the IL-17 class. I think that is a great class of agents.”

Generalized pustular psoriasis is a condition for which there is a dearth of effective therapies, noted Dr. Barankin “We have never had a specific therapy for generalized pustular psoriasis,” said Dr. Barankin.

“Spesolimab is an anti-IL-36 inhibitor which reverses GPP quickly, and most patients attain dramatic improvement within the first week. It’s

not a common condition that we see, but when we do see patients with it, it can be very serious and even life threatening. Unlike

Dr. Ben Barankin

Dr. Catherine Zip

spesolimab, the medications we currently use act slowly and do not have as good a side effect profile.

IL inhibitors for AD Dr. Kyle Cullingham, a dermatologist in Saskatoon and medical director of Saskatoon Dermatology Centre, said dermatologists can potentially look forward to using biologic agents for conditions such as HS. “IL-17 molecules, such as secukinumab or ixekizumab, are being studied for the treatment of HS,” said Dr. Cullingham. “Bimekizumab, which is a new molecule that [has] become available for treating psoriasis, is also being trialled for HS. That is really exciting.”

IL inhibitors are also being explored for their ability to manage conditions such as prurigo nodularis and notalgia paresthetica, condi-

Dr. Kerri Purdy

Dr. Kyle Cullingham

tions in which itch features prominently, noted Dr. Cullingham. “They [prurigo nodularis and notalgia paresthetica] are conditions that work on similar pathways as eczema. Often times, these [conditions] can be the result of chronic eczema. If we can treat them upstream [of the pathway], then we can possibly obtain great results.”

Another biologic option now available in Canada for AD is tralokinumab, a biologic agent that targets IL-13. It received approval in 2021 and will be available for prescription for moderate-to-severe AD, expanding biologic options beyond dupilumab for AD. “No head-tohead trials vs. dupilumab have been

conducted,” noted Dr. Zip. Dr. Cullingham added he will be taking part in a Phase IV study on tralokinumab. “It’s exciting to have another biologic for atopic dermatitis,” he said. “We will get patients on the medication and see how they fare over the next year. This is an opportunity for real-world data.”

The exploration of many molecules as potential treatments for HS is very encouraging, according to Dr. Cullingham. “There are quite a few molecules being studied for HS,” he said, noting the only approved treatment to date is adalimumab.

“We haven’t had a lot of new options, so it’s exciting to see.”

Non-proprietary and brand names of therapies: tildrakizumab (Ilumya, Sun Pharma); risankizumab (Skyrizi, AbbVie); guselkumab (Tremfya, Janssen); bimekizumab (BIMZELX, UCB Canada); adalimumab (Humira, AbbVie); ustekinumab (Stelara, Janssen); secukinumab (Cosentyx, Novartis); spesolimab (not approved in Canada); imsidolimab (not approved in Canada); ixekizumab (Taltz, Lilly); tralokinumab (Adtralza, LEO Pharma); dupilumab (Dupixent, Sanofi, Regeneron).

What THE LAY PRESS is saying about . . .

Dermatology news your patients may be reading

HOW TO PROPERLY SHAVE TO REMOVE PEACH FUZZ More women are now shaving their faces. While most might not have dense beards, peach fuzz has become a trait that many females want to eliminate. An article published in Cosmopolitan (Mar. 24, 2022) listed tips for women to safely shave their faces and remove that unwanted peach fuzz.

The magazine consulted with three specialists based in the U.S. who provided some insights into female face shaving and who also recommended some specific products.

All specialists agree that face shaving is safe for women and debunked myths such as the common belief that hair will grow thicker after being shaved. The article also provides a step-by-step guide and recommends specific products that have been dermatologically tested, according to the author.

MEET INTUITIVE SKINCARE In the past few years, the concept of intuitive eating has become popular.

Intuitive eating proposes that a person should listen to their body’s hunger cues and should trust their own body to make food choices that feel good for them. Intuitive skincare proposes a similar idea. A report published in The Toronto Star (Apr. 5, 2022) covers this concept, by stating that consumers should always listen to their skin when trying a new product. While the report focuses heavily on a particular brand of products, the general idea is that while a product might work perfectly for some people, everyone’s skin reacts differently and it is important to pay attention to the outcomes.

HOW ‘SKIN OF COLOUR DERMATOLOGY ’ IS MAKING HEALTHCARE MORE INCLUSIVE Too often, people of colour get misdiagnosed or have delayed diagnoses because skin diseases present differently in various skin tones. A report published on the website SELF (Mar. 25, 2022) addresses this problem by showing the case of a black woman who was incorrectly diagnosed with vitiligo when she actually had a rare form of blood cancer that also affects the skin. Not only are many doctors unfamiliar with how certain conditions look in darker patients, but textbooks are also lacking diversity. This is slowly changing, as some medical schools now have ethnic skin centers to provide better dermatologic care to people of colour and to minimize gaps in medical training.

Clinics dedicated to skin of colour patients are also expanding. According to the report, a more diverse approach to skincare and dermatology is helping to make healthcare more inclusive.

THE 21 BEST MOISTURIZERS WITH SPF FOR 2022 Most skincare routines include a moisturizer and a good facial sunscreen. While applying more than one product isn’t too time-consuming, it is a kill-two-birds-with-onestone situation if a moisturizer is already infused with SPF. An article published in the New York Post (Apr. 12, 2022) listed some recommended moisturizers with SPF for this year. It is important to note that, aside from recommending specific products, the article also has some recommendations regarding sun protection in general. According to Dr. Jesse M. Lewin, a dermatologic surgeon based in New York and spokesperson for The Skin Cancer Foundation, “Daily sunscreen use is an important part of a complete sun protection strategy that includes seeking shade during peak sun hours (10 am to 4 pm) and covering up with UPF clothing, wide-brimmed hats and UVblocking sunglasses.” He also added that it is important to use an SPF product year-round and not just during the summer.

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PRESCRIPTION ANTIHISTAMINE COVERED BY MOST PRIVATE INSURANCE PLANS • P-glycoprotein inhibitors may increase plasma levels of BLEXTEN® in patients with moderate or severe renal impairment; co-administration should be avoided • BLEXTEN® should be avoided during pregnancy unless advised otherwise by a physician • A study was performed to assess the effects of BLEXTEN® and bilastine 40 mg on real time driving performance compared to placebo.Bilastine did not affect driving performance differently than placebo following day one or after one week of treatment.

However, patients should be informed that very rarely some people experience drowsiness, which may affect their ability to drive or use machines.

For more information: Please consult the product monograph at https://www.miravohealthcare.com/wp-content/uploads/2021/08/ Blexten-PM-ENG-Aug2021.pdf for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The product monograph is also available by calling 1-866-391-4503.

As of August 31, 2021, the estimate from internal data of patient exposure is based on units sold of the defined daily dose of 20 mg bilastine and the mean treatment duration of 3 weeks.

Reference: 1. Blexten® Product Monograph. Aralez Pharmaceuticals Canada Inc. 2021.

bilastine tablets 20 mg Aralez Pharmaceuticals Canada Inc.* 6733 Mississauga Road, Suite 800 Mississauga, Ontario L5N 6J5 *d/b/a Miravo Healthcare

© 2022. BLEXTEN is a registered trademark of FAES used under license by Aralez Pharmaceuticals Canada Inc.

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POSEDUCATIONAL TGRAD UATE SUPPLEMENT Assessment of efficacy and safety of UV-based therapy for psoriasis: A network meta-analysis of randomized controlled trials Yajia Li,1 Ziqin Cao,2 Jia Guo,1 Qiangxiang Li,3,4,5 Wu Zhu,1,6 Yehong Kuang,1,6 and Xiang Chen1,6

Department of Dermatology, Hunan Key Laboratory of Skin Cancer and Psoriasis; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China 2Department of Spine Surgery, the Xiangya Hospital, Central South University, Changsha, Hunan, China 3National Clinical Research Center for Geriatric Disorders of Xiangya Hospital, Central South University (Sub-centre of Ningxia), Yinchuan, Ningxia Hui Autonomous Region 750001, China 4Ningxia Geriatric Disease Clinical Research Center, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750001, China 5 Hunan People's Hospital, Geriatrics Institute of Hunan Province, Changsha, China, Changsha 410002, China 6National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China 1

ABSTRACT Background: Previous studies have proven that ultraviolet (UV)-based phototherapy, including UVB or psoralen UVA (PUVA), and their combination therapies, is effective for psoriasis treatment.

Objective: To compare the clinical efficacy and adverse events (AEs) of different UV-based phototherapy in psoriasis.

Methods: PubMed, Cochrane Library, Scopus and Embase were systematically searched. A random-effect model network meta-analysis with frequentist framework was performed, and results were reported as risk ratios (RRs) with 95% CI. The main variable for assessing effectiveness and safety are PASI 75 response and withdrawal due to AEs. Ranking effects were calculated by surface under the cumulative ranking analysis (SUCRA).

Results: Thirty-two studies involving a total of 2,120 psoriasis patients were included in this network meta-analysis. Overall, no significant difference was reported with respect to withdrawal due to AEs or incidence of erythema. The relatively safest strategy was combined adjuvant therapy with PUVA (cPUVA), especially PUVA combined with calcium/vitamin D derivatives (RR 0.98, 95% CI [0.30–3.17], SUCRA=80.8%). Both cPUVA (RR 1.39, 95% CI [1.00–1.94]) and combined adjuvant therapy with UVB (cUVB) (RR 1.27, 95% CI [1.03–1.57]) showed a superior effect than the monotherapy of UVA or UVB, respectively. PUVA combined with vitamin D and its derivatives (PAVD) ranked highest concerning clinical effect and safety (clusterank value=7393.2).

Conclusions: The efficacy of all the combination therapy regimens was significantly superior to that of UV monotherapy, without significant differences in tolerability and safety. cUVB and cPUVA, and particularly the combination of UVA with calcium/vitamin D derivatives, was ranked as the overall safest and most effective phototherapy method.

P

INTRODUCTION

soriasis is known as a common, immune-related, chronic inflammatory skin disorder and the estimated prevalence was ranging from 0.51% to 11.4% in worldwide adults.1 Plaque psoriasis is the most common type, and most psoriasis patients suffering from the mildto-moderate disease can be treated with topical treatments, whereas severe cases require additional therapeutic op-

tions.2 Systemic therapies, including oral retinoids, as well as biologics or phototherapy, are used for the longterm treatment of psoriasis.3 Ultraviolet (UV)-based phototherapy with UVB or psoralen UVA (PUVA) is also a well-established and generally effective treatment for chronic plaque psoriasis employing UV light with or without photosensitizers.4 Although systemic and biological treatments are strongly recommended for severe and diffuse skin diseases,

these medications can determine systemic side effects and immunosuppression. Based on the evidence from the U.S. National Psoriasis Foundation, UVB phototherapy (broadband [BB] or narrow-band [NB]) is suggested for patients with moderate-to-severe psoriasis before adopting treatments with systemic and biologic agents. Also, PUVA is indicated for patients with poor NB-UVB control and high psoriasis area and severity index (PASI) scores.5 Among phototherapy regimens for psoriasis, broadband UVB (BB-UVB) has the longest history and narrowband UVB (NB-UVB) represents the first-line phototherapy treatment, also in combination with other regimens.6 These UV-based phototherapies, along with their combination with other treatments, are thought to be effective treatments for many psoriasis patients, leading to an urgent demand for comparative studies of efficacy referring to clinical decision making. A meta-analysis published in 2013 comparing the efficacy of localized phototherapies showed that topical PUVA treatment is more effective than nonlaser targeted UVB phototherapy.7 Almutawa, et al summarized characteristics of UV-based therapies, indicating that PUVA monotherapy showed higher effectiveness than UVBbased therapy in determining complete skin clearance of patients with moderate-to-severe plaque-type psoriasis.8 Since then, there have been several randomized controlled trials (RCTs) on demonstrating and comparing the efficacy, safety or tolerability of monotherapies and UV-based combinatorial therapies. However, no comprehensive studies evaluating relative UV efficacy and tolerability have been carried out so far. Although several head-to-head trials exist, RCTs have not considered all possible pairwise combinations of UV-based therapies with agents, or simultaneous direct comparisons of multiple treatments.

In this study, we performed a network meta-analysis (NMA) collecting direct and indirect evidence from several RCTs simultaneously.9 Specifically, the achievement of PASI 75 response (75% or more reduction in PASI score

from baseline) in the short-term period of treatment was chosen to measure its efficacy since it is indicative of both severities and involved area of psoriatic lesions, as well as it is evaluated and described in most reported trials and reviews.10,11 This study was aimed to compare the efficacy and tolerability of UV-based therapies, used as monotherapy or in combination with various drugs and remedies, including systemic treatments, skin lubricants, vitamins and vitamin derivatives, for the treatment of moderate-to-severe psoriasis.

We also considered the absolute effects of therapies to provide information supporting clinical decision-making and care planning.

MATERIALS AND METHODS The study protocol was registered in the international prospective register of systematic reviews (https://www.crd.york.ac.uk/PROSPERO), number CRD42021232906. The research question in the manuscript was how different UV-based phototherapies impacted the efficacy and safety for the treatment of psoriasis.

Data sources and searches DWe designed and conducted this study following the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guideline.12 Two authors (Y.L. and Z.C.) independently and systematically searched the following queries in PubMed, Cochrane Library, Scopus and Embase, from January 1980 to January 2021: “psoriasis” OR “psoriatic” AND “light therapy” OR “phototherapy” and “ultraviolet radiation A” OR “UVA” OR “ultraviolet radiation A with psoralen” OR “PUVA” OR “ultraviolet radiation B” OR “UVB” OR “excimer” OR “TL-01” OR “PUVA” AND “combination” OR “UVB” AND “combination”.

Additional potentially eligible studies were screened by further reviewing reference lists of identified articles. There was no restriction on the language of publication.

Study selection The following studies were used in our NMA: 1. studies analysing psoriasis pa-

Reprinted with permission ©2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Content has been edited to conform with the Canadian Press Publication Style Guide.

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POSTGRADUATE EDUCATIONAL SUPPLEMENT

Figure 1: Structure of network formed by interventions. The lines between treatment nodes indicate the direct comparisons made within randomized controlled trials. The solid line means direct comparisons and the dashed line means indirect comparisons. (A) Main network meta-analysis. (B) Subgroup analysis. tients undergoing phototherapy; 2. studies comparing two or more different treatment strategies; 3. studies describing RCTs with prospective parallel-group design; 4. studies reporting at least one of the following outcomes: PASI, withdrawal due to adverse events (AEs), and incidence of erythema. On the contrary, we excluded: 1. low-quality studies according to the corresponding quality assessment tools; 2. dose-escalation studies made using only one treatment strategy; 3. animal studies, in vitro biomechanical studies, cadaver studies, case-control studies, reviews, systematic reviews and metaanalyses, conference abstracts, letters and analyses not comprising original data.

For studies with insufficient data, we contacted the corresponding authors. We chose to contact the corresponding authors when relatively to data of studies were presented as figures and not as numeric data in the manuscript text or tables. If no response was received, two current authors (Y.L. and Z.C.) independently extrapolated data from the graphs/figures. If that was not possible the study was excluded. All disagreements were resolved according to the discussion with the third author (J.G.).

Data extraction and quality assessment Next, the qualities of the included studies were assessed by evaluating the methodological quality and the bias risk of RCTs, calculated by using the Cochrane risk of the bias assessment tool.13 The following six indices were evaluated and divided into unclear, low or high risk of bias, including sequence generation, allocation concealment, blinding, incomplete outcome data, selection outcome reporting and other sources of bias.

We extracted the relevant data from studies, including the first author, year of publication, the number of participants, mean age, gender ratio, type or degree of psoriasis, mean of follow-

Figure 2: Forest plots incorporated direct comparisons and indirect comparisons of main network meta-analysis. (1) PASI 75 response. (2) PASI 75 and above response. (3) Absolute PASI improvement. (4) Withdrawal due to AEs. (5) Incidence of erythema.

(A: PUVA; B: UVB; C: cPUVA; D: cUVB; E: cAB). up and outcomes data. The data in the intention-to-treat analysis were preferred for avoiding the influence of withdrawal bias if present.

OUTCOME MEASURES The primary efficacy endpoints were the percentage of patients achieving PASI 75 or a PASI response greater than PASI 75 if the latter was not available. As for the other assessment standards, we only included trials reporting the complete clearance of the disease or nearly clearance (90% improvement from the baseline). Those trials that reported PASI 75, PASI 90 or clearance were grouped into PASI 75 and above.

Considering that the differences between the baseline values of each included study may reduce the reliability of the results and conclusions, the changes from the baseline value of PASI (PASI improvement) at the last follow-up were calculated (mean±SD) and used to reconfirm the findings from PASI 75 or above. For studies not reporting PASI improvement, the correlation coefficient method recommended by Cochrane Handbook13 was used to calculate the changes.

Considering the impact of patient compliance on the treatment effect in clinical practice, withdrawal due to AEs was chosen as the primary safety endpoint, and to estimate treatment tolerability. The secondary safety endpoint was erythema, the most common AEs related to UV-based therapies. The risk ratio (RR) with 95% CI was used to compare the relative safety of treatments.

STATISTICAL ANALYSIS Random-effects NMA were conducted by using Stata/MP software version 14.0 (Stata Corp, College Station, Texas) with a frequentist framework.

The proportional variance-covariance matrix data were pooled using the random-effects multivariate meta-re-

gression, whereas the model fit was evaluated by the restricted maximumlikelihood method.14 Inconsistencies were assessed with global inconsistency tests and nodesplit tests, and only if both results reported no significant inconsistency (p>0.05), the consistency model was adopted. If inconsistency was reported in any network, a sensitivity analysis was used to identify the source of inconsistency and to exclude studies from the network. Publication biases for each network were evaluated by funnel plots, and for networks whose funnel plots showed possible asymmetry, the presence of publication bias was assessed by the egger’s test. The relative efficacy and safety of different phototherapy strategies were ranked using surface under the cumulative ranking (SUCRA) probabilities15 and cluster-ranking plots were constructed to determine the optimal choice for multiple outcome indicators. Further subgroup analysis was conducted for exploring the optimal combination of drugs. Data relative to four subgroups of drugs, including vitamin A and its derivatives, vitamin D and its derivatives, skin lubricants, and system treatments, were obtained.

Differences between treatments were considered significant when the 95% CI did not contain 1 for RR or 0 for SMD and WMD. p<0.05 was considered as significant level in statistics.

RESULTS Literature selection Thirty-two studies were included following the systematic screening of the literature (Figure S1).16–47 In the main network analysis, five different phototherapy strategies were identified and analysed: PUVA, UVB, combined adjuvant therapy with PUVA (cPUVA), combined adjuvant therapy with UVB (cUVB) and the combination of PUVA with UVB (cAB). According to the category and activity mechanism

of the adjuvant treatment, nine subgroups were identified and analysed: PUVA, UVB, PAVA (PUVA combined with vitamin A and its derivatives), PAVD (PUVA combined with vitamin D and its derivatives), UBVA (UVB combined with vitamin A and its derivatives), UBVD (UVB combined with vitamin D and its derivatives), UBST (UVB combined with systematic treatments), UBSL (UVB combined with skin lubricants) and cAB. The network plot of the main network analysis and subgroup analysis are shown in Figure 1.

Study characteristics The analysis involved a total of 2,120 psoriasis patients. The median age of subjects was 41.5 years (interquartile distance 37.32−45.00), and the median percentage of male patients was 61.6% (ranging 35.71–100.00%) (Table S1). Details on quality and bias-risk assessments of all studies are shown in Table S2. The funnel plots of the main network meta-analysis and subgroup analysis are shown in Figures S1 and S2, respectively.

MAIN NETWORK META-ANALYSIS PASI 75 response A total of 19 trials with 1,476 patients were included in this network. No inconsistency was detected after the application of the consistency model. Based on the SUCRA values, the cPUVA group obtained the highest PASI 75 response (SUCRA=86.0%), followed by cUVB (SUCRA=79.0%) and UVB (SUCRA=32.0%), whereas the lowest PASI 75 was achieved following CAB treatment (SUCRA=26.1%). The cPUVA group was numerically higher than PUVA group (RR 1.39, 95% CI [1.00–1.94]), whereas the cUVB group outnumbered the UVB group (RR 1.27, 95% CI [1.03–1.57]).

PASI 75 and above response A total of 32 trials involving 2,120 pa-

Table 1: Detailed results of main network analysis.

[1.15–3.01]) and UVB (RR 1.87, 95% CI [1.09–3.19]) treatments, and UBST was more efficacious than UVB (RR 1.58, 95% CI [1.08–2.31]).

PASI 75 and above response

Table 1: The league plots of main network meta-analysis (from the top left to the bottom right, higher comparator vs. lower comparator). tients were included in this network. No significant inconsistencies were found in applying the consistency model. Similar to PASI 75 response results, cPUVA and cUVB determined a better response in patients (SUCRA=81.1 and 78.4%, respectively), whereas UVB was the treatment less effective (SUCRA=23.3%).

Significant differences were only found between cPUVA- and PUVA-treated groups (RR 1.23, 95% CI [1.01–1.50]), cUVB and UVB (RR 1.20, 95% CI [1.06– 1.37]).

PASI improvement For this network, we only analyzed data on 844 patients in 14 trials, so these results should be explained with caution.

No significant inconsistency was detected by using the consistency model.

Although the funnel plot of this network showed dubious asymmetry, Egger’s tests did not report any significant publication bias or small-study effect (p=0.661). From these analyses, the cPUVA group resulted to respond significantly better than PUVA (SMD 2.31, 95% CI [0.48–4.13]) or UVB (SMD 2.17, 95% CI [0.15–4.18]) groups, and the cUVB-treated group achieved better PASI responses than UVB-treated group (SMD 1.22, 95% CI [0.05–2.39]). According to SUCRA, cPUVA and cUVB ranked highest in efficacy (SUCRA=89.5 and 67.4%, respectively), whereas PUVA was the lowest-ranked treatment (SUCRA=19.4%).

Safety outcomes Networks relative to 23 trials (1,410 patients) and 20 trials (1,361 patients) reporting withdrawal due to AEs, and incidence of erythema, respectively were assessed. The consistency model application did not reveal inconsistencies for the two analyzed networks.

No significant difference was reported relative to withdrawal due to AEs. The PUVA group showed the highest withdrawal rate according to SUCRA (reference, SUCRA=46.6%), while cUVB (RR 0.87, 95% CI [0.23–3.31], SUCRA=54.9%) and cAB (RR 0.83, 95% CI [0.02–41.33], SUCRA=52.5%) showed the lowest rate.

No significant difference was also reported for the incidence of erythema.

Based on the SUCRA ranking, UVB and cUVB showed less incidence of erythema (RR 0.75 95% CI [0.27–2.09], SUCRA=65.8% and RR 0.75, 95% CI [0.26–2.19], SUCRA=61.0%, respectively), whereas cAB group showed the worst response (reference, SUCRA=31.5%). SUCRA values of main network analyses are shown in Table 1, and the forest plots in Figures 2 and 3.

According to the cluster-rank results, cUVB and cPUVA ranked highest with respect to effect (PASI 75 response) and safety (withdrawal due to AEs) combined parameters (clusterank value=4,337.1 and 4,016.2, respectively), whereas PUVA ranked lowest (clusterank value=1,253.5) (Figure S4). In Table 2, the league plots relative to differences between network meta-analysis groups are shown.

SUBGROUP ANALYSIS PASI 75 response A total of 20 trials with 1,500 patients were included in this network. The application of the consistency model did not reveal any inconsistency. PAVD treatment was potentially the best therapeutical strategy according to SUCRA (SUCRA=91.5%), followed by UBST (SUCRA=83.0%) and UBSL (SUCRA=54.5%) therapies. UVB was the less effective treatment (SUCRA=24.8%).

In addition, PAVD was significantly better than both PUVA (RR 1.86, 95% CI

Table 3: Detailed results of subgroup analysis.

A total of 32 trials with 2,120 patients were involved in this network. Also for this analysis, no significant inconsistency was found. PAVD and UBST groups showed a better response, in terms of achievement of a PASI 75 and above response (SUCRA=97.4 and 70.8%), and, similarly to what was observed for PASI 75 response network, UVB ranked lowest (SUCRA=18.2%).

PAVD treatment determined a better response than PAVA (RR 1.69, 95% CI [1.05–2.72]), UBSL (RR 1.72, 95% CI [1.04–2.84]), cAB (RR 1.78, 95% CI [1.04– 3.03]), PUVA (RR 1.86, 95% CI [1.22– 2.84]) and UVB (RR 1.88, 95% CI [1.21–2.92]) therapies. UBST was also better than UVB treatment (RR 1.26, 95% CI [1.01–1.57]).

PASI improvement Fourteen trials with 844 patients could be included in this network. Although the application of the Egger’s test revealed no concern (p=0.668), the publication bias and small-study effect could likely represent critical issues. Again, the consistency model was adopted. PAVDand UBSL-treated patients showed a better response as compared to patients undergone the other treatments.

According to SUCRA, PAVD and UBSL ranked highest (SUCRA=98.3 and 88.9%, respectively), whereas UVB ranked lowest (SUCRA=18.6%).

Safety outcomes Two networks relative to 23 trials (1,410 patients) reporting the withdrawal due to AEs and 20 trials (1,361 patients) reporting the incidence of erythema, respectively, were assessed. No significant inconsistencies were detected using the consistency model.

No significant difference was reported with respect to withdrawal due to AEs or incidence of erythema. In line with SUCRA result of withdrawal rate, PAVA and PAVD were the worst- and the best-tolerated treatments (reference, SUCRA=32.2% and RR 0.98, 95% CI [0.30–3.17], SUCRA=80.8%, respectively). UBVA group reported the highest incidence of erythema (reference,

SUCRA=23.2%), whereas UBVD the lowest (RR 0.42, 95% CI [0.12–1.51], SUCRA=83.6%).

According to the cluster-rank results, PAVD and UBST ranked highest concerning clinical effect (PASI 75 response) and safety (withdrawal due to AEs) (clusterank value=7,393.2 and 5,419.9, respectively), whereas UVB ranked lowest (clusterank value=1,205.3) (Figure S5). SUCRA values are shown in Table 3, and forest plots of the subgroup analysis are reported in Figures S6 and S7. The league plots of subgroup analysis are presented in Tables S3–S5.

DISCUSSION We conducted the first network metaanalysis based on high-quality RCTs comprehensively comparing the effects and tolerability of UV-based phototherapy strategies for the moderate-to-severe psoriasis treatments. This NMA represents a valuable comparison of all currently licenced or commonly used UVB or PUVA phototherapies and their combinations with other treatments.

Our findings are largely in accordance with and based on evidence from those previously published guidelines and systematic reviews. A previous systematic literature review by Archier, et al48 showed that although PUVA tended to clear plaque-type psoriasis more efficiently than NB-UVB, dermatologists prefer the latter treatment as the firstline phototherapy, due to cutaneous carcinogenic risk by PUVA and the easier administration procedure of UVB. In parallel, a meta-analysis by Almutawa, et al reported that topical PUVA was superior to non-laser-targeted UVB phototherapy in terms of effectiveness.7 However, though we found the PUVA group showed the highest withdrawal rate according to SUCRA, there was no significant difference when comparing PUVA with UVB treatments in terms of efficacy and safety. This discrepancy might be due to the lack of sufficient studies summarizing all kinds of adverse effects, such as pruritus, nausea, vertigo, headache, etc. The information available in the analysed studies permitted only to conclude that both groups developed cutaneous erythematous reaction, which is an adverse effect particularly common in phototherapy. In our opinion, the severe side-effects of PUVA observed more frequently in the PUVA group could not be ignored. Markham, et al35 also reported that NB-UVB (TL-01) had fewer side effects than PUVA in treatments of patients with chronic plaque psoriasis. Interestingly, the efficacy of all the combination therapy regimens was significantly higher than that observed using UV in monotherapy. cPUVA also determined a more substantial improving skin lesions without a lower safety than PUVA Therefore, cPUVA could be used for moderate-to-

POSTGRADUATE EDUCATIONAL SUPPLEMENT

Figure 3: Forest plots of network comparisons of main network meta-analysis. (1) PASI 75 response. (2) PASI 75 and above response. (3) Absolute PASI improvement. (4) Withdrawal due to AEs. (5) Incidence of erythema. severe psoriasis cases as an alternative to UVB therapies if ineffective. We also found that when compared with PAVA, PUVA, UVB and CAB, the PUVA therapies administered together with calcium/vitamin D derivatives, such as calcipotriene, showed higher efficacy and were more tolerated than single treatments. Consistently, a recent metaanalysis showed that targeted UVB combined with calcipotriene was more efficacious than targeted UVB alone, and the efficacy of combination therapy could be related to the analogous and complementary roles associated with calcipotriene on UVB.49 Calcipotriol cream is used to treat plaque psoriasis and is generally preferred to the ointment formulation as it is less greasy.

UVB and Calcipotriene can increase the level of 1,25-dihydroxy vitamin D3 and inhibit the proliferation of the epidermal cell. Therapeutic effects of vitamin D3 analogues persist after PUVA or NBUVB irradiation, and calcipotriene ointment addition to PUVA determines a UVA sparing effect as well as clearing of psoriatic lesions with low UVA accumulation.50,51 Combination of PUVA with calcipotriene reduces the UVA dosage required for clearance of psoriasis, thus decreasing the long-term risk of cutaneous malignancy and increasing the efficacy of treatment. Our study could not produce corresponding data on the accumulated dose required for clearance, and more clinical studies are necessary to obtain this evidence.

Importantly, both the outcomes of efficacy and safety were considered together in cluster-ranking plots and joint rankings and provided absolute effect estimates to help clinical decision making: (1) The efficacy of all the combination therapy regimens was significantly higher than that of UV monotherapy, and there was no significant difference in their tolerability and safety; (2) cPUVA showed an optimal efficacy to improve skin lesions, especially when combined with calcium/vitamin D derivatives to

treat moderate-to-severe psoriasis; (3) PUVA and UVB treatments have no significant differences in efficacy and safety, nor the combination of PUVA with UVB increase efficacy. On the contrary, PUVA and UVB co-treatment increased the risk of erythema according to SUCRA results; (4) PAVD regimen showed higher efficacy compared with PAVA, PUVA, UVB, and CAB treatments, as well as it was the best-tolerated so that it could have the potential to be the optimal choice in the clinical decision; (5) based on cluster-rank analysis, cPUVA (PAVD) and cUVB (UBST) are the safest and most effective phototherapy methods to treat psoriasis.

On the other hand, our study had some limitations. Although observational studies and other non-randomized control trials (nRCTs) also play an indispensable role in evaluating the effectiveness and safety, especially the long-term effects of therapy, we only included high-quality RCTs to avoid the unmanageable confounding factors existing in observational studies and other nRCTs. This may be one of the reasons for the relatively insufficient number of articles included in this study. Therefore, publication bias represented a non-negligible problem for our study, also deduced from funnel plots showing dubious asymmetry and resulting from small-study effects.

In addition, considering withdrawal due to AEs, we also included studies with no events in both treatment arms in the network. The Cochrane Handbook recommends omitting studies with rare events, but it is controversial whether this alters the bias evaluations and the accuracy of the combined estimation. Therefore, we included such trials and used a 0.5 zerocell correction. However, we should explain these results with caution. It should be considered that though SUCRA is widely used to rank the effects of treatments, it may also ignore whether the difference between treat-

ments has clinical significance. Although one treatment may be ranked as the best treatment, the absolute difference between the best one and other treatments may be very small. Therefore, also SUCRA results should be interpreted cautiously.15 Finally, some factors can influence outcomes but cannot be adjusted or eliminated statistically.

These include differences in comorbidities, duration and dose of treatment, time of follow-up and severity of psoriasis among populations in this study.

For instance, some of the included studies have not reported the accurate duration or severity of psoriasis so that due to insufficient relevant data, it is almost impossible to adjust these factors.

CONCLUSION Our research provides comprehensive comparative data for moderate to severe psoriasis patients in UV-based treatment. Our results revealed that the efficacy of all the combination therapy regimens was significantly superior to that of UV monotherapy, without significant differences in tolerability and safety. cUVB and cPUVA, and particularly the combination of UVA with calcium/vitamin D derivatives, was ranked as the overall safest and most effective phototherapy methods in UV-based treatment strategies. cPUVA and cUVB, especially combined with calcium/vitamin D derivatives, are both safe and effective treatments for psoriasis and have the potential for the first choice in the treatment of moderate-to-severe psoriasis. However, more high-quality trials are necessary for confirming our findings, and there will be detailed comparisons of relative efficacy and safety in future NMAs.

ACKNOWLEDGEMENTS The authors express their gratitude to EditSprings (https://www.editsprings.com/) for the expert linguistic services provided.

This manuscript is not under review with any other journal now and has not been

published on any other journal previously. The authors thank for grants from the National Science Foundation of China (81170823); the Hunan Province Philosophy and Social Science Foundation Project of 2018 (18YBA325); Project of Hunan Provincial Department of Education in 2018 (160546); Hunan Provincial Health and Health Commission Scientific Research Fund Project (C2019055); Hunan Provincial Department of Finance 2017 project (Xiangcai Finance Agency [2017] 61); Ningxia Hui Autonomous Region Philosophy and Social Science Planning Year Project (19NXAGL01); Hunan Province’s “225” project training discipline leader project for high-level health professionals; The Special Project of Central Guidance for Local Science and Technology Development, 2020YDDF0043.

DISCLOSURE STATEMENT The authors declare that they have no competing interests.

AUTHOR CONTRIBUTIONS Yajia Li: Visualization, Data curation, Software, Writing- Original draft preparation; Ziqin Cao: Visualization, data curation, software, writing- original draft preparation; Jia Guo: software, validation; Qiangxiang Li: supervision; Wu Zhu; conceptualization, methodology, data curation and supervision. Yehong Kuang; conceptualization, methodology, writing-editing and revision; Xiang Chen: conceptualization, methodology, writing-editing and revision; All the authors: Writing-reviewing and editing; All authors participated in the research and gave final approval to the version submitted for publication.

DATA AVAILABILITY STATEMENT Data generated or analysed during this study are included in this published article. The datasets generated during and/or analyzed during this study are available from the corresponding author on reasonable request.

ADDITIONAL INFORMATION Funding This study was supported by the National Natural Science Foundation of China (82173426, 81573049, 81974479, 81773329, 81430075, 81830096, 82073447, 8207121425), Key R & D Program of Hunan Province (2018SK2082), National key R & D program (2018YFC0117004).

REFERENCES 1.Michalek IM, Loring B, John SM: A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatol Venereol 2017; 31(2):205–212.

2. Griffiths CE, Christophers E, Barker JN, et al: A classification of psoriasis vulgaris according to phenotype. Br J Der-

matol 2007; 156(2):258–262.

3. Elmets CA, Lim HW, Stoff B, et al: Joint American academy of DermatologyNational psoriasis foundation guidelines of care for the management and treatment of psoriasis with phototherapy. J Am Acad Dermatol 2019; 81(3):775–804.

4. Vieyra-Garcia PA, Wolf PA: Deep dive into UV-based phototherapy: mechanisms of action and emerging molecular targets in inflammation and cancer. Pharmacol Ther 2021; 222:107784.

5. Leon A, Nguyen A, Letsinger J, et al: An attempt to formulate an evidencebased strategy in the management of moderate-to-severe psoriasis: a review of the efficacy and safety of biologics and prebiologic options.

Expert Opin Pharmacother 2007; 8(5):617– 632.

6. Menter A, Korman NJ, Elmets CA, et al: Guidelines of care for the management of psoriasis and psoriatic arthritis: section 5. Guidelines of care for the treatment of psoriasis with phototherapy and photochemotherapy.

J Am Acad Dermatol 2010; 62(1):114–135.

7. Almutawa F, Thalib L, Hekman D, et al: Efficacy of localized phototherapy and photodynamic therapy for psoriasis: a systematic review and Metaanalysis.

Photodermatol Photoimmunol Photomed 2015; 31(1):5–14.

8. Almutawa F, Alnomair N, Wang Y, et al: Systematic review of UV-based therapy for psoriasis. Am J Clin Dermatol 2013; 14(2):87–109.

9. Mills EJ, Thorlund K, Ioannidis JP: Demystifying trial networks and network Meta-analysis. BMJ 2013; 346:f2914.

10. Schmitt J, Zhang Z, Wozel G, et al: Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: metaanalysis of randomized controlled trials. Br J Dermatol 2008; 159(3):513–526.

11. Hampton P, Halliday A, Aassi M, et al: 12-week secukinumab treatment is consistently efficacious for moderate-to-severe psoriasis regardless of prior biologic and non-biologic systemic treatment: post-hoc analysis of six randomized trials. J Eur Acad Dermatol Venereol 2021; 35(4):928–937.

12. Brent MB, Brüel A, Thomsen JS: Animal models of disuse-induced bone loss: study protocol for a systematic review. Syst Rev 2020; 9(1):185.

13. Higgins JPT, Thomas J, Chandler J, et al (Eds.): Cochrane handbook for systematic reviews of interventions. 2nd ed. Chichester: John Wiley & Sons; 2019.

14. White IR, Barrett JK, Jackson D, et al: Consistency and inconsistency in network Meta-analysis: model estimation using multivariate Meta-regression. Res Synth Methods 2012; 3(2):111–125.

15. Rücker G, Schwarzer G: Ranking treatments in frequentist network Metaanalysis works without resampling

methods. BMC Med Res Methodol 2015; 15:58.

16. Yones SS, Palmer RA, Garibaldinos TT, et al: Randomized double-blind trial of the treatment of chronic plaque psoriasis: efficacy of psoralen-UV-a therapy vs narrowband UV-B therapy.

Arch Dermatol 2006; 142(7):836–842.

17. Dawe RS, Cameron H, Yule S, et al: A randomized controlled trial of narrowband ultraviolet B vs bath-psoralen plus ultraviolet a photochemotherapy for psoriasis. Br J Dermatol 2003; 148(6):1194–1204.

18. Lauharanta J, Juvakoski T, Lassus A: A clinical evaluation of the effects of an aromatic retinoid (tigason), combination of retinoid and PUVA, and PUVA alone in severe psoriasis. Br J Dermatol 1981; 104(3):325–332.

19. Torras H, Aliaga A, López-Estebaranz JL, et al: A combination therapy of calcipotriol cream and PUVA reduces the UVA dose and improves the response of psoriasis vulgaris. J Dermatolog Treat 2004; 15(2):98–103.

20. Gordon PM, Diffey BL, Matthews JN, et al: A randomized comparison of narrow-band TL-01 phototherapy and PUVA photochemotherapy for psoriasis. J Am Acad Dermatol 1999; 41(5):728–732.

21. Ozdemir M, Engin B, Baysal I, et al: A randomized comparison of acitretinnarrow-band TL-01 phototherapy and acitretin-psoralen plus ultraviolet a for psoriasis. Acta Derm Venereol 2008; 88(6):589–593.

22. Mortazavi H, Khezri S, Hosseini H, et al: A single blind randomized clinical study: the efficacy of isotretinoin plus narrow band ultraviolet B in the treatment of psoriasis vulgaris. Photodermatol Photoimmunol Photomed 2011; 27(3):159–161.

23. Dover JS, McEvoy MT, Rosen CF, et al: Are topical corticosteroids useful in phototherapy for psoriasis? J Am Acad Dermatol 1989; 20(5):748–754.

24. Ramsay CA, Schwartz BE, Lowson D, et al: Calcipotriol cream combined with twice weekly broad-band UVB phototherapy: a safe, effective and UVBsparing antipsoriatric combination treatment. The Canadian calcipotriol and UVB study group. Dermatology 2000; 200(1):17–24.

25. Behrens S, Grundmann-Kollmann M, Schiener R, et al: Combination phototherapy of psoriasis with narrowband UVB irradiation and topical tazarotene gel. J Am Acad Dermatol 2000; 42(3):493–495.

26. Dayal S, Mayanka, Jain VK: Comparative evaluation of NBUVB phototherapy and PUVA photochemotherapy in chronic plaque psoriasis. Indian J Dermatol Venereol Leprol 2010; 76(5):533–537.

27. Al-Hamamy HR, Al-Mashhadani SA, Mustafa IN: Comparative study of the effect of narrowband ultraviolet B phototherapy plus methotrexate vs. narrowband ultraviolet B alone and methotrexate alone in the treatment of plaque-type psoriasis. Int J Dermatol

2014; 53(12):1531–1535.

28. Ghiasi M, Ebrahimi S, Lajevardi V, et al: Efficacy and safety of pioglitazone plus phototherapy versus phototherapy in patients with plaque type psoriasis: a double blinded randomized controlled trial. J Dermatolog Treat 2019; 30(7):664–667.

29. Bagel J: LCD plus NB-UVB reduces time to improvement of psoriasis vs. NBUVB alone. J Drugs Dermatol 2009; 8(4):351–357.

30. Brockow T, Schiener R, Franke A, et al: A pragmatic randomized controlled trial on the effectiveness of low concentrated saline spa water baths followed by ultraviolet B (UVB) compared to UVB only in moderate to severe psoriasis. J Eur Acad Dermatol Venerol 2007; 21(8):1027–1037.

31. Asawanonda P, Nateetongrungsak Y: Methotrexate plus narrowband UVB phototherapy versus narrowband UVB phototherapy alone in the treatment of plaque-type psoriasis: a randomized, placebo-controlled study. J Am Acad Dermatol 2006; 54(6):1013–1018.

32. Mahajan R, Kaur I, Kanwar AJ: Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque-type psoriasis–a randomized singleblinded placebo-controlled study. J Eur Acad Dermatol Venereol 2010; 24(5):595– 600.

33. Calzavara-Pinton P: Narrow band UVB (311 nm) phototherapy and PUVA photochemotherapy: a combination.

J Am Acad Dermatol 1998; 38(5 Pt 1):687– 690.

34. Chauhan PS, Kaur I, Dogra S, et al: Narrowband ultraviolet B versus psoralen plus ultraviolet a therapy for severe plaque psoriasis: an Indian perspective. Clin Exp Dermatol 2011; 36(2):169–173.

35. Markham T, Rogers S, Collins P: Narrowband UV-B (TL-01) phototherapy vs oral 8-methoxypsoralen psoralenUV-a for the treatment of chronic plaque psoriasis. Arch Dermatol 2003; 139(3):325–328.

36. Brands S, Brakman M, Bos JD, et al: No additional effect of calcipotriol ointment on low-dose narrow-band UVB phototherapy in psoriasis. J Am Acad Dermatol 1999; 41(6):991–995.

37. Rim JH, Choe YB, Youn JI: Positive effect of using calcipotriol ointment with narrow-band ultraviolet B phototherapy in psoriatic patients. Photodermatol Photoimmunol Photomed 2002; 18(3):131– 134.

38. Gahalaut P, Soodan PS, Mishra N, Rastogi MK, et al: Clinical efficacy of psoralen + sunlight vs. combination of isotretinoin and psoralen + sunlight for the treatment of chronic plaquetype psoriasis Vulgaris: a randomized hospital-based study. Photodermatol Photoimmunol Photomed 2014; 30(6):294–301.

39. Menkes A, Stern RS, Arndt KA: Psoriasis treatment with suberythemogenic

ultraviolet B radiation and a coal tar extract. J Am Acad Dermatol 1985; 12(1 Pt 1):21–25.

40. Saurat JH, Geiger JM, Amblard P, et al: Randomized double-blind multicenter study comparing acitretin-PUVA, etretinate-PUVA and placebo-PUVA in the treatment of severe psoriasis.

Dermatologica 1988; 177(4):218–224.

41. Snellman E, Klimenko T, Rantanen T: Randomized half-side comparison of narrowband UVB and trimethylpsoralen bath plus UVA treatments for psoriasis. Acta Derm Venereol 2004; 84(2):132–137.

42. Aggarwal P, Aggarwal K, Jain VK: Tacalcitol: a useful adjunct to narrow band ultraviolet B phototherapy in psoriasis. J Dermatolog Treat 2016; 27(6):546– 551.

43. Trott J, Gerber W, Hammes S, et al: The effectiveness of PUVA treatment in severe psoriasis is significantly increased by additional UV 308-nm excimer laser sessions. Eur J Dermatol 2008; 18(1):55–60.

44. Abdallah MA, El-Khateeb EA, AbdelRahman SH: The influence of psoriatic plaques pretreatment with crude coal tar vs. petrolatum on the efficacy of narrow-band ultraviolet B: a halfvs.-half intra-individual doubleblinded comparative study.

Photodermatol Photoimmunol Photomed 2011; 27(5):226–230.

45. Molin L: Topical calcipotriol combined with phototherapy for psoriasis. The results of two randomized trials and a review of the literature. Calcipotriol-UVB study group. Dermatology 1999; 198(4):375–381.

46. Neumann NJ, Mahnke N, Korpusik D, et al: Treatment of palmoplantar psoriasis with monochromatic excimer light (308-nm) versus cream PUVA. Acta Derm Venereol 2006; 86(1):22–24.

47. Van TN, Van TH, Minh PPT, et al: Efficacy of narrow - band UVB phototherapy versus PUVA chemophototherapy for psoriasis in Vietnamese patients. Open Access Maced J Med Sci 2019; 7(2):227–230.

48. Archier E, Devaux S, Castela E, et al: Efficacy of psoralen UV-a therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol 2012; 26(3):11–21.

49. Gu X, Shen M, Zhao S, et al: Combination of targeted UVB phototherapy and calcipotriene versus targeted UVB alone in psoriasis: systematic review and Meta-analysis of randomized controlled trials. J Dermatolog Treat 2020; 1–5.

50. Adachi Y, Uchida N, Matsuo T, et al: Clinical effect of vitamin D3 analogues is not inactivated by subsequent UV exposure. Photodermatol Photoimmunol Photomed 2008; 24(1):16–18.

51. Youn JI, Park BS, Chung JH, et al: Photoprotective effect of calcipotriol

upon skin photoreaction to UVA and UVB. Photodermatol Photoimmunol Photomed 1997; 13(3):109–114.

Research of Note Research of Note

HAIR LOSS AND COVID -19 HAIR LOSS AND COVID -19 he authors of this systematic review aimed to characterize the types, incidence, he authors this systematic aimed to characterize the types, timing, and of clinical outcomesreview of Covid-19-associated alopecia.

A totalincidence, of 41 artitiming, and clinical outcomes of Covid-19-associated alopecia.

A total of 41 articles published between Nov. 2019 and Aug. 2021 were identified that described cles published between Nov. 2019 and Aug. 2021 were identified that described 1,826 patients with Covid-19 and alopecia.The most common types of alopecia identified 1,826 androgenetic patients with Covid-19 alopecia.The mostmale), common typeseffluvium of alopecia identified were alopecia and (AGA) (30.7%, 86.4% telogen (TE) (19.8%, were androgenetic alopecia (AGA) (30.7%, 86.4% male), telogen effluvium (TE) 19.3% male), and alopecia areata (AA) (7.8%, 40.0% male). AGA preceded Covid-19(19.8%, symp19.3% TE male), alopecia (AA)by(7.8%, 40.0% male).AA AGA preceded Covid-19 symptoms. was and usually newlyareata triggered Covid-19 (93.6%). usually occurred in patients toms.

TE was usually newly triggered by Covid-19 (93.6%).

AA usually occurred in patients with pre-existing disease (95.1%). withThey pre-existing disease (95.1%). conclude that AGA may be a risk factor for severe Covid-19, whereas TE presents They conclude that AGA be a risk factoras forasevere Covid-19, whereas TE presents as a sequela of Covid-19. AAmay generally occurs relapse in patients with pre-existing as a sequela of Covid-19. AA generally occurs as a relapse in patients with pre-existing alopecia. alopecia.

B Nguyen, A Tosti: Alopecia in patients with COVID-19: A systematic review and meta-analysis, in

T

B Nguyen, A Tosti: Alopecia in patients with COVID-19: AJAAD systematic review and International (Junemeta-analysis, 2022;7:67-77)in.

JAAD International (June 2022;7:67-77).

UV-BASED PSORIASIS TX REVIEWED UV-BASED PSORIASIS TX REVIEWED esearchers reviewed 32 studies totalling 2,120 psoriasis patients to compare the esearchers reviewed 32 studies totalling psoriasisphototherapy. patients to compare clinical efficacy and adverse events (AEs)2,120 of UV-based PASI 75 the reclinical efficacy and adverse events (AEs) of UV-based phototherapy.

PASI 75 response and withdrawal due to AEs were the main variables for assessing effecsponse and withdrawal due to AEs were the main variables for assessing effectiveness and safety. tiveness and safety.

The authors found no significant difference regarding withdrawal due to AEs or inciTheofauthors foundThe no significant difference regarding withdrawal due to AEs incidence erythema. safest strategy was combined adjuvant therapy withorPUVA dence of erythema.

The safest strategy was combined adjuvant therapy with PUVA (cPUVA), especially PUVA combined with calcium/vitamin D derivatives. Both cPUVA and (cPUVA), especially combined with calcium/vitamin D derivatives. cPUVA and combined adjuvant PUVA therapy with UVB (cUVB) showed a superior effectBoth to UVA or UVB combined adjuvant with UVB (cUVB) showed a superior(PAVD) effect ranked to UVA highest or UVB monotherapy.

PUVA therapy combined with vitamin D and its derivatives monotherapy.

PUVA combined with vitamin D and its derivatives (PAVD) ranked highest in clinical effect and safety. in clinicalYeffect and safety.

Li, Z Cao, J Guo, Q Li, W Zhu, Y Kuang, X Chen: Assessment of efficacy and safety of

R

Y Li, Z Cao, J Guo, Li, W Zhu, Y Kuang,meta-analysis X Chen: Assessment of efficacy and safety of UV-based therapy forQpsoriasis: a network of randomized controlled trials, UV-based therapy for psoriasis: a network in meta-analysis of randomized trials, Annals of Medicine (2022; controlled 54(1):159-169). in Annals of Medicine (2022; 54(1):159-169).

Clinicaluse usenot notmentioned mentionedelsewhere elsewhereininthe thepiece piece Clinical Clinical use not mentioned elsewhere in the piece RINVOQshould shouldnot notbebeused usedinincombination combinationwith withother otherJanus Januskinase kinase RINVOQ RINVOQ should not be used in combination other Janus kinase (JAK) inhibitors, immunomodulating biologicswith (e.g., biologic DMARDs), (JAK) inhibitors, immunomodulating biologics (e.g., biologic DMARDs), (JAK) inhibitors, immunomodulating biologics (e.g., biologic DMARDs), withpotent potentimmunosuppressants immunosuppressantssuch suchasasazathioprine azathioprineand andcyclosporine. cyclosporine. ororwith or with potent immunosuppressants such as azathioprine and cyclosporine.

Thesafety safetyand andeffeff icacyofofRINVOQ RINVOQininadolescents adolescentsweighing weighing<40 <40kgkg The icacy The safety and eff icacy of RINVOQ in adolescents weighing <40 have kg andininchildren childrenaged aged0 0totoless lessthan than1212years yearswith withatopic atopicdermatitis dermatitis have and and in children aged 0 to less than 12 years with atopic dermatitis have notyetyetbeen beenestablished. established. not not yet been established.

Cautionshould shouldbebeused usedwhen whentreating treatinggeriatric geriatricpatients patientswith withRINVOQ. RINVOQ. Caution Caution should be used when treating geriatric patients with RINVOQ. Mostserious seriouswarnings warningsand andprecautions precautions Most Most serious warnings and precautions Seriousinfections: infections:Patients Patientstreated treatedwith withRINVOQ RINVOQare areatatincreased increasedrisk risk Serious Serious infections: Patients treated with RINVOQ are at increased risk developing seriousinfections infections thatmay may lead hospitalization death. forfor developing serious that lead totohospitalization orordeath. for developing serious infections that may lead to hospitalization or death.

Mostpatients patientswho whodeveloped developedthese theseinfections infectionswere weretaking takingconcomitant concomitant Most Most patients who developed these infections were taking concomitant immunosuppressantssuch suchasasmethotrexate methotrexateororcorticosteroids. corticosteroids. serious immunosuppressants IfIfaaserious immunosuppressants such as methotrexate or corticosteroids.

If a serious infectiondevelops, develops,interrupt interruptRINVOQ RINVOQuntil untilthe theinfection infectionisiscontrolled. controlled. infection infectioninfections develops, interrupt RINVOQ until the (TB), infection is controlled.

Reported infectionsinclude includeactive active tuberculosis (TB),which which maypresent presentwith with Reported tuberculosis may Reported infections include active tuberculosis (TB), which may present pulmonary or extrapulmonary disease; invasive fungal infections, including pulmonary or extrapulmonary disease; invasive fungal infections, includingwith pulmonary or extrapulmonary disease; invasive fungal infections, cryptococcosis andpneumocystosis; pneumocystosis; and bacterial, viral (includingincluding herpes cryptococcosis and and bacterial, viral (including herpes cryptococcosis and pneumocystosis; and bacterial, viral (including herpes zoster),and andother otherinfections infectionsdue duetotoopportunistic opportunisticpathogens. pathogens.

Testpatients patients zoster), Test zoster), and other infections due to opportunistic pathogens.

Test patients latentTBTBbefore beforeRINVOQ RINVOQuse useand andduring duringtherapy. therapy.Consider Considertreatment treatmentfor for forforlatent for latent TB before RINVOQ use and during therapy.

Consider treatment for latent infection prior to RINVOQ use.

Do not initiate treatment in patients with latent infection prior to RINVOQ use. Do not initiate treatment in patients with latentinfections infection prior to RINVOQ use.

Do not initiate treatment in patients with active infectionsincluding including chronic localized infections.

Carefully consider active chronic ororlocalized infections.

Carefully consider active infections including chronic or localized infections.

Carefully consider therisks risksand andbenefits benefitsofoftreatment treatmentprior priortotoinitiating initiatingtherapy therapyininpatients patients the thechronic risks and benefits ofinfections. treatment prior to monitor initiating therapy infor patients with chronic recurrent infections.Closely Closely monitorpatients patientsfor signsand and with oror recurrent signs with chronic or recurrent infections.

Closely monitor patients for signs and symptomsofofinfection infectionduring duringand andafter aftertreatment, treatment,including includingthe thepossible possible symptoms symptoms ofofinfection duringwho and after treatment, including the possible development ofTBTBininpatients patients whotested tested negativefor forlatent latentinfection infection prior development negative prior development of TB in patients who tested negative for latent infection prior initiatingtherapy. therapy. totoinitiating to initiating therapy.

Malignancies:Lymphoma Lymphomaand andother othermalignancies malignancieshave havebeen beenobserved observedinin Malignancies: Malignancies: Lymphoma and other malignancies have been observed in patients treatedwith with RINVOQ. patients treated RINVOQ. patients treated with RINVOQ.

Diagnostic Quiz Diagnostic Quiz

Photo courtesy Wikimedia Photo courtesy of of Wikimedia Commons Commons

JJo ou urrn na all C Cllu ub b

THE CHRONICLE of SKIN & ALLERGY THE CHRONICLE of SKIN & ALLERGY

A. Parakeratosis pustulosa A. Parakeratosis pustulosa B. Lichen planus . Lichen planus CB . Onychomycosis CD. .Onychomycosis Nail psoriasis D. Nail psoriasis

THE EDITORS invite your participation in this THE EDregular ITORS feature invite your participation of the journal. in this regular the journal.

Please feature send allofimages and Please send all images correspondence to: and correspondence Medical Editor,to: Medical The Chronicle of Editor, Skin & Allergy The Chronicle of Skin & Suite Allergy 555 Burnhamthorpe Road, 306, 555 Burnhamthorpe Road, Suite 306, Toronto, Ont. M9C 2Y3.

Toronto, Ont. M9C 2Y3.

Telephone: (416) 916-2476 Telephone: (416) 916-2476 E-mail: health@chronicle.org E-mail: health@chronicle.org

Correct answer D Nail psoriasis Correct answer D Nail psoriasis

34• April/May 2022 34• April/May 2022

Thrombosis:Thrombosis, Thrombosis,including includingdeep deepvenous venousthrombosis, thrombosis,pulmonary pulmonary Thrombosis: Thrombosis: Thrombosis, including deep venousininthrombosis, pulmonary embolism, andarterial arterialthrombosis, thrombosis, have occurred patientstreated treated with embolism, and have occurred patients with embolism, and arterial thrombosis, have occurred in patients treated JAK inhibitors, including RINVOQ, for inflammatory conditions.

Many of these JAK inhibitors, including RINVOQ, for inflammatory conditions. Many ofwith these JAK inhibitors, including RINVOQ, for inflammatory conditions.

Many of these adverse events were serious and some resulted in death.

Consider the risks adverse events were serious and some resulted in death. Consider the risks adverse events were seriouspatients and some resulted inat death.

Consider risks and benefits prior treating patients who maybe be atincreased increased risk.the Patients and benefits prior tototreating who may risk.

Patients and benefits prior to treating patients who may be at increased risk.

Patients withsymptoms symptomsofofthrombosis thrombosisshould shoulddiscontinue discontinueRINVOQ RINVOQtreatment treatment and and with with symptoms of thrombosis should discontinue RINVOQ treatment and should bepromptly promptly evaluatedand and treated appropriately. should be evaluated treated appropriately. should be promptly evaluated and treated appropriately.

Otherrelevant relevantwarnings warningsand andprecautions precautions Other Other relevant warnings and precautions Immunizations Increasesininlipid lipidparameters, parameters, •• Immunizations • •Increases • Immunizations •including Increasestotal, in lipid parameters, including total, low-density low-density Viralreactivation, reactivation,including including herpes herpes •• Viral including total, low-density • (e.g., Viralherpes reactivation, including herpes lipoprotein, andhigh-density high-density lipoprotein, and (e.g., herpeszoster) zoster) and hepatitis hepatitis and BB lipoprotein, and high-density (e.g., herpes zoster) and hepatitis B lipoproteincholesterol cholesterol lipoprotein • Malignancies • Malignancies lipoprotein cholesterol • Malignancies Gastrointestinalperforations perforations • •Gastrointestinal Increasesinincreatine creatinephosphokinase phosphokinase •• Increases • Gastrointestinal perforations • Increases in creatine phosphokinase Hematologicevents events • •Hematologic Monitoringand andlaboratory laboratory tests tests •• Monitoring • Hematologic events • Monitoring and laboratory tests Liverenzyme enzymeelevation elevation • •Liver • Pregnant Pregnantwomen women • • Liver enzyme elevation • Pregnant women Patientswith withactive active • •Patients Reproductivehealth health •• Reproductive •hepatitis Patients with active • Reproductive health hepatitisBBororCCinfection infection • Breast-feeding • Breast-feeding hepatitis B or C infection • Breast-feeding Patientswith withsevere severehepatic hepatic • •Patients Geriatrics(≥65 (≥65years yearsof ofage) age) •• Geriatrics •impairment Patients with severe hepatic impairment • Geriatrics (≥65 years of age) Pediatrics(<12 (<12years yearsof ofage) age) •• Pediatrics impairment Concomitantuse usewith withother otherpotent potent • Pediatrics (<12 years of age) • •Concomitant • Asian patients • Asian patients •immunosuppressants, Concomitant use withbiologic other potent immunosuppressants, biologic • Asian patients immunosuppressants, biologic DMARDs,ororother otherJAK JAKinhibitors inhibitors DMARDs, DMARDs, or other JAK inhibitors Formore moreinformation information For For more information Pleaseconsult consultthe theProduct ProductMonograph Monographatatrinvoq.ca/pm rinvoq.ca/pmfor forimportant important Please Please consult the Product Monograph rinvoq.ca/pm for and important information relating adverse reactions,atdrug drug interactions, anddosing dosing information relating totoadverse reactions, interactions, information relating to adverse reactions, drug interactions, dosing informationwhich whichhave havenot notbeen beendiscussed discussedininthis thispiece. piece.The Theand Product information Product information which have not been discussed in this piece.

The Product Monographisisalso alsoavailable availableby bycalling callingus usatat1-888-704-8271.

1-888-704-8271.

Monograph Monograph is also available by calling us at 1-888-704-8271.

The first once-daily oral JAK inhibitor therapy indicated in AD*†

POWERFUL EFFICACY DEMONSTRATED in moderate to severe AD RINVOQ is indicated for the treatment of adults and adolescents 12 years of age and older with refractory moderate to severe atopic dermatitis (AD) who are not adequately controlled with a systemic treatment (e.g., steroid or biologic) or when use of those therapies is inadvisable. RINVOQ can be used with or without topical corticosteroids.

Not a real patient, for illustrative purposes only.

In the Measure Up 1 study:‡

RINVOQ 15 mg demonstrated significant improvement in skin clearance (as measured by proportion of patients with EASI 75; co-primary endpoint & EASI 90; secondary endpoint) vs. placebo at Week 161,2 • EASI 75: 69.6% (n/N=196/281) vs. 16.3% (n/N=46/281) of patients achieved EASI 75 with RINVOQ 15 mg vs. placebo (p<0.0001, multiplicity-controlled).

• EASI 90: 53.1% (n/N=149/281) vs. 8.1% (n/N=23/281) of patients achieved EASI 90 with RINVOQ 15 mg vs. placebo (p<0.0001, multiplicity-controlled).

A rapid improvement in skin clearance was achieved for RINVOQ 15 mg compared to placebo (defined as EASI 75 by Week 2; secondary endpoint)1,2 • EASI 75: 38.1% (n/N=107/281) vs. 3.6% (n/N=10/281) of patients achieved EASI 75 at Week 2 with RINVOQ 15 mg vs. placebo (p<0.0001, multiplicity-controlled).

A greater proportion of patients treated with RINVOQ 15 mg achieved clinically meaningful itch reduction (≥4-point reduction in Worst Pruritus NRS; secondary endpoint) compared to placebo treatment group at Week 16 • ≥4-point reduction in Worst Pruritus NRS: 52.2% (n/N=143/274) vs. 11.8% (n/N=32/272) of patients achieved a ≥4-point reduction in Worst Pruritus NRS with RINVOQ 15 mg vs. placebo (p<0.0001, multiplicity-controlled).

At Week 16, a greater proportion of patients treated with RINVOQ 15 mg achieved clinically meaningful improvement in emotional state (ADerm-IS emotional state domain score improvement from baseline; secondary endpoint) compared to placebo group (RINVOQ 15 mg [n/N=142/227]: 62.6%; placebo [n/N=42/212]: 19.8%; p<0.0001, RINVOQ vs. placebo, multiplicity-controlled). * Comparative clinical significance has not been established. † Please see Product Monograph for additional dosing and administration information. ‡ Measure Up 1 was a 16-week, randomized, double-blind, multicentre, placebo-controlled study that included adolescent and adult patients with refractory moderate to severe atopic dermatitis not adequately controlled by topical medication(s). At baseline, patients had an vIGA-AD score ≥3 in the overall assessment of AD (erythema, induration/papulation, and oozing/crusting) on an increasing severity scale of 0 to 4, an EASI score ≥16 (composite score assessing extent and severity of erythema, edema/papulation, scratches and lichenification across 4 different body sites), a minimum BSA involvement of ≥10%, weekly average Worst Pruritus NRS ≥4, and a DLQI score of ≥4 (in patients aged ≥16). Patients received RINVOQ 15 mg or RINVOQ 30 mg once daily, or placebo.

ADerm-IS: Atopic Dermatitis Impact Scale; BSA: body surface area; DLQI: Dermatology Life Quality Index; EASI: Eczema Area and Severity Index; JAK: Janus kinase; NRS: Numerical Rating Scale; vIGA-AD: validated Investigator’s Global Assessment for Atopic Dermatitis.

References: 1. RINVOQ Product Monograph. AbbVie Corporation. 2. Guttman-Yassky E, Teixeira HD, Simpson EL, et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet 2021;397(10290):2151-68.

© AbbVie Corporation CA-RNQD-210046A – April 2022

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PRECISION

WHERE IT MATTERS. PERFORMANCE IN

ACNE CARE.

The 1st topical retinoid indicated to treat facial and truncal acne.1-3 • Trifarotene molecule precisely binds to the most relevant RAR in acne (RAR-ɣ)1 • Patients may see significant results in facial acne in four weeks 3 • Patients reported substantial improvements in self-confidence, social life, and emotional well-being4 with improvement of their acne AKLIEF.ca Indication and clinical use: AKLIEF® (trifarotene 50 mcg/g) cream is indicated for the topical treatment of acne vulgaris of the face and/or trunk in patients 12 years of age and older.

Safety and effectiveness have not been established in geriatric patients (≥65 years).

Contraindications: • Eczema or seborrheic dermatitis • Pregnancy or women planning a pregnancy Most serious warnings and precautions: • For external use only, not for ophthalmic use • Pregnancy or planning a pregnancy: Rare reports of birth defects associated with topical retinoids during pregnancy. Women of child-bearing potential should be informed of potential risks and use effective birth-control measures

Other relevant warnings and precautions: • Discontinue use if allergic/hypersensitivity reactions occur • Avoid contact with eyes, lips, angles of the nose, mucous membranes, abraded skin, open wounds, cuts, and eczematous and sunburned skin • Avoid use of other dermatologic medications and potentially irritating topical products that have a strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes • Non-comedogenic cosmetics should be used • Treatment area should not be covered with dressings or bandages • Weather extremes, such as wind or cold, may be more irritating • Exposure to excessive sunlight, including sunlamps, should be avoided or an effective sunscreen and protective clothing are recommended

• Certain cutaneous signs and symptoms can be expected with use • Use of electrolysis, “waxing,” and chemical depilatories for hair removal should be avoided • Caution when taking drugs with known photosensitizers • Avoid use on chest during breastfeeding For more information: Please consult the AKLIEF® Product Monograph at https://pdf.hres.ca/dpd_pm/00054047.

PDF for important information relating to adverse reactions, interactions, and dosing information, which have not been discussed in this advertisement.

The Product Monograph is also available by calling us at 1-800-467-2081.

References: 1. AKLIEF® Product Monograph. Galderma Canada Inc. November 25, 2019. 2. Aubert J, et al. Nonclinical and human pharmacology of the potent and selective topical retinoic acid receptor-γ agonist trifarotene. Br J Dermatol.

2018;179(2):442-456. 3. Tan J, et al. Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne. J Am Acad Dermatol. 2019;80(6):1691-1699. 4. Blume-Peytavi U, et al. Long-term safety and efficacy of trifarotene 50 μg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne. J Eur Acad Dermatol Venereol. 2021;34(1):166-173.

RAR-ɣ, retinoic acid receptor gamma AKLIEF® is a registered trademark of Galderma Canada Inc. Galderma Canada Inc. Thornhill, Ontario CA-AFC-2100112