and ruxolitinib (a JAK1/2 inhibitor), FDA-approved to treat myelofibrosis and polycythemia vera, have been used to treat recalcitrant alopecia areata. One study found oral tofacitinib therapy was associated with hair regrowth in approximately 64% of patients after a three-month period. The same study found that 32% of patients achieved greater than 50% improvement in their Severity of Alopecia Tool (SALT) score.6 Another study also reported regrowth with 58% achieving greater than 50% improvement in their SALT score for a four to 18-month duration.7 Oral ruxolitinib was associated with 75% of patients reaching a SALT score greater than 50%.8 Topical tofacitinib and ruxolitinib can be effective10 and theoretically are less likely to have systemic side effects.9 JAK inhibitors can be used to treat severe and recalcitrant alopecia areata in patients who do not respond to conventional therapies such as topical or intralesional steroids, minoxidil, or topical immunotherapy. JAK inhibitor therapy may need to be continuous since alopecia frequently recurs with drug discontinuation.3 These medications are associated with increased risk of urinary tract infections, varicella zoster reactivation, cytopenias, and mild increases in cholesterol but do not appear to increase the risk of malignancy. Obtaining a complete blood count, creatinine, hepatic functional panel, hepatitis B, hepatitis C, and tuberculosis screening is recommended prior to starting treatment.10 Cautions when Using Biologics and JAK Inhibitors
Biologic medications can have rare but serious side effects and, in some cases, have been associated with increased risks of infections, demyelinating neurologic conditions, and malignancy. It’s important to note that most biologic drugs require baseline and annual tuberculosis screening in addition to other specific laboratory tests to ensure patient safety. The associated adverse side effects of systemic JAK inhibitors include infections, drug eruptions, hematological abnormalities, and hyperlipidemia. On the other hand, topical JAK inhibitors have a low MetroDoctors
incidence of side effects which can be taken into consideration when prescribing treatment. Specifically, the most common side effects of dupilumab are injection site reactions, upper respiratory tract infections and conjunctivitis. The conjunctivitis, which in actual practice seems to be the most common side effect, is perplexing. At this time it’s unknown if this is related to the dupilumab specifically or is part of the impaired barrier and inflammation that comes along with atopic dermatitis. The use of artificial tears is recommended prophylactically, and loprednol ophthalmic drops or ointment does help to treat this if it occurs. So far, there have been no reports of increased risk of malignancy, but long-term data are lacking. Like many biologics, there is a risk of immunogenicity, or antibody formation, to the dupilumab, but in the clinical studies this seemed very low, about 6% overall, with only 2% that were persistent and drug-neutralizing. There is no recommended screening or ongoing monitoring required with dupilumab; however, any patient with a known parasitic or helminth infection should not use dupilumab until they are clear of the infection. The use of dupilumab in pediatric patients (those less than 18 years old, and pregnant or lactating women) has not been well studied. Live vaccines are not recommended while on dupilumab; however, the response to non-live vaccines did not seem to be altered or affected by dupilumab and are recommended as needed. Another challenge for these types of drugs may be financial. Although insurances do cover the costs of therapy, for some with high deductible plans it may be prohibitive. For example, dupilumab costs approximately $3,000 a month while systemic tofacitinib costs approximately $4,300 a month. One month’s supply of topical tofacitinib, however, costs approximately $330. The Place of Biologics and JAK Inhibitors within Dermatology Treatment
is a target for new psoriasis medications. Another biologic to treat atopic dermatitis that targets IL-4, IL-17, and IL-31 is also in development. Systemic and topical JAK inhibitors are also being considered for a broader span of dermatologic conditions, including vitiligo, atopic dermatitis and psoriasis. Stay tuned as more research is published, and exciting new applications of these innovative medications are introduced. Phillip Keith, MD and Kathryn Barlow, MD are board certified dermatologists practicing with Dermatology Consultants. Dr. Barlow received her medical degree from the Chicago Medical School and completed her Dermatology residency at Loyola University. Dr. Keith received his medical degree from the Medical College of Wisconsin and completed his Dermatology residency at Mayo Clinic Rochester. References: 1. Rahman S, et al. The pathology and immunology of atopic dermatitis. Inflamm Allergy Drug Targets 2011 Dec;10(6):486-96. 2. Gooderham, MJ et al. Dupilumab: A review of its use in the treatment of atopic dermatitis. J Am Acad Dermatol 2018;78:S28-36. 3. Strazzula et al. Alopecia areata disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatology 2018; 78:1-14. 4. De Medeiros AKA, Speeckaert R, Desmet E, Van Gele M, De Schepper S, Lambert J, JAK3 as an emeriging target for topical treatment of inflammatory skin diseases. PloS One, 2016; 11: e0164080. 5. Schwartz DM, Bonelli M, Gadina M, O’Shea JJ. Type I/II cytokines, Jaks, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016; 12(1): 25-36. 6. Kennedy Crispin M, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insgiht. 2016;1 (15):e89776. 7. Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: at study of 90 patients. J Am Acad Dermatol. 2017; 76:22-28. 8. Mackay-Wiggan J, Jabbari A, Nguyen N, et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe-alopecia areata. JCI Insight. 2016;1(15):e89790. 9. Bayart C, et al. Topical Janus kinase inhibitors for the treatment of pediatric alopecia areata. J am Acad Dermatol 2017;77;167-170. 10. Damsky W, King B. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol 2017;76:736-744.
There are several promising new treatments on the horizon. IL-23, for example,
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