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Transforming Care in Inflammatory and Autoimmune Diseases Hospital for Special Surgery Division of Rheumatology 2013 Annual Report

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Perioperative Medicine: A Model Program Preparing Patients for Orthopaedic Surgery

CATCH-US: The Canadian Early Arthritis Cohort Study Comes to America

From Drug Targets to New Therapies for Inflammatory and Autoimmune Diseases

Linda A. Russell, MD page 5

Vivian P. Bykerk, MD page 6

Franck J. Barrat, PhD page 8

Point of View: Our Experts’ Perspectives on Complex Cases page 11

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Hospital for Special Surgery Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopaedics, rheumatology and rehabilitation. HSS is nationally ranked No. 1 in orthopaedics, No. 4 in rheumatology, and No. 5 in geriatrics by U.S.News & World Report (2013-14), and is the first hospital in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center three consecutive times. Located in New York City, HSS also serves patients in the regional area with physician offices in Greenwich, Long Island, and Queens, and serves Florida patients with an outpatient rehabilitation office in South Florida. Patients choose to come to Hospital for Special Surgery from across the United States and from around the world. HSS has one of the lowest infection rates in the country. HSS is a member of the NewYork-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College and as such all Hospital for Special Surgery medical staff are faculty of Weill Cornell. The Hospital’s Research Division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at www.hss.edu.

on the cover Vivian P. Bykerk, MD, has focused her career in rheumatology in understanding the basic principles of early inflammatory arthritis and, at the same time, caring for patients who can benefit from her research [see article, page 6]. The unique role of human plasmacytoid dendritic cells in immunity is a key focus of the laboratory of Franck J. Barrat, PhD, and is at the basis of many potential clinical applications [see article, page 8].

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Transforming Care in Inflammatory and Autoimmune Diseases At the foundation of the mission of the Division of Rheumatology is a commitment to advancing the field through innovation in basic science endeavors and the translation of discoveries to the clinical arena. The Hospital’s physicians and scientists are closely aligned in our goal to transform care in inflammatory and autoimmune diseases. And the extraordinary breadth and depth of the scientific and clinical expertise of our faculty is enabling Hospital for Special Surgery to address some of the most challenging issues in diagnosis and treatment in medicine today.

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LEADERSHIP REPORT

FEATURES 5 Perioperative Medicine: A Model Program Preparing Patients for Orthopaedic Surgery 6 CATCH-US: The Canadian Early Arthritis Cohort Study Comes to America 8 From Drug Targets to New Therapies for Inflammatory and Autoimmune Diseases 11 Point of View: Our Experts’ Perspectives on Complex Cases 16

PROFESSIONAL STAFF

17 ENDOWED CHAIRS, PROFESSORSHIPS, AND FELLOWSHIPS

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SELECTED PUBLICATIONS

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CONTACT INFORMATION

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A Message from the Physician-in-Chief and Chair, Division of Rheumatology Promoting the Integration of Science and Medicine The Division of Research, directed by Steven R. Goldring, MD, MACR, Chief Scientific Officer, has undergone an important transformation in the past few years, advancing integrative and collaborative programs among our scientists and clinicians and across the Hospital’s disciplines to ensure the effective transfer of new knowledge. We are very fortunate to have a cohort of investigators who are experienced in the basic science of inflammatory and autoimmune disorders and concurrently involved in the care of patients who develop them. Their combined expertise is key to accelerating the application of laboratory discoveries to therapeutic innovations, and their ongoing work continues to inform the development of new treatments and attract competitive funding from the National Institutes of Health, the Arthritis Foundation, the Lupus Research Institute, as well as industry that supports science and medicine. This funding support includes:

Dr. Mary K. Crow

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uring the past year, the Division of Rheumatology at Hospital for Special Surgery continued to build on the strengths of its many clinical and scientific endeavors toward the fundamental goal of improving outcomes for patients with autoimmune and inflammatory diseases. With 36 rheumatologists, many who serve in the dual role as physician scientists, the Division takes great pride in the concentration of expertise it is able to bring to bear on the care of patients with osteoarthritis and rheumatoid arthritis; those with lupus, vasculitis, progressive systemic sclerosis, and other complex, multisystem diseases; and patients who present with difficult diagnostic challenges. In 2012, our rheumatology practices realized more than 33,000 office visits, an increase of 7 percent over 2011, and another 3,500 clinic visits. The Division recently evaluated the structure of our clinics to determine ways to improve patient access to care. As a result, we initiated a clinic dedicated exclusively to new patients and a primary care rheumatology clinic focused on evaluation of clinical problems typically encountered in the context of primary care medical practices. The new clinic provides timely access to patients referred from the general medicine practices of NewYorkPresbyterian/Weill Cornell Medical Center. Members of the rheumatology faculty also provide consultations for inpatients at NewYork-Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center. In addition, our Perioperative Medicine program is responsible for all of the pre- and post-surgical medical care of the more than 26,000 patients who undergo orthopaedic surgery procedures at HSS each year [see article, page 5].

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• An NIH/National Institute of Dental and Craniofacial Research grant to Lionel B. Ivashkiv, MD, David H. Koch Chair for Arthritis and Tissue Degeneration Research, to investigate molecular mechanisms of pathological bone damage that occurs in musculoskeletal and inflammatory diseases • An NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases grant, in collaboration with the University of Nebraska, to develop novel nanomedicines to diagnose and treat inflammatory disorders led by Ed Purdue, PhD, and Dr. Steven Goldring • Novel Research Grants from the Lupus Research Institute to Xiaoyu Hu, MD, PhD, for studies to elucidate how interferons are regulated in lupus and identify therapies to limit their production, and to Jane E. Salmon, MD, Collette Kean Research Chair and Director of the HSS Lupus and Antiphospholipid Syndrome Center of Excellence, to determine the mechanisms for kidney damage caused by lupus antibodies • An Arthritis National Research Foundation Grant to George D. Kalliolias, MD, PhD, to study the role of tumor necrosis factor alpha in inducing synovial fibroblast activation

Dr. Lionel B. Ivashkiv

Dr. Steven R. Goldring

Dr. Jane E. Salmon

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Dr. George D. Kalliolias

Dr. Alessandra B. Pernis

Dr. Carl P. Blobel

• An Exploratory/Developmental Research Grant from the NIH/ National Institute of Arthritis and Musculoskeletal and Skin Diseases to study an inhibitor to reverse T cell dysfunction in SLE awarded to Dr. Jane Salmon, in collaboration with Alessandra B. Pernis, MD, Peter Jay Sharp Chair in Lupus Research The Alliance for Lupus Research and Pfizer’s Centers for Therapeutic Innovation have formed a partnership to support novel and promising translational research projects in the area of lupus. This highly competitive program recently funded the work of Dr. Jane Salmon and Carl P. Blobel, MD, PhD, on a potential new drug target to protect against kidney damage and my laboratory’s research on identifying therapeutic targets that treat or prevent lupus flare. In collaboration with Boehringer Ingelheim, Dr. Lionel Ivashkiv is working on identifying pathways contributing to RA pathogenesis and Dr. Goldring, with Vivian P. Bykerk, MD, Susan M. Goodman, MD, and Lisa A. Mandl, MD, MPH, is pursuing research in mechanisms of inflammatory bone resorption in the spondyloarthropathies. Both projects seek to further drug development in these areas. We are pleased to welcome Franck J. Barrat, PhD, to our Autoimmunity and Inflammation Program. An experienced translational basic scientist with expertise in the function and regulation of immune system cells in the pathogenesis of lupus, Dr. Barrat was previously with Roche as a Distinguished Scientist in the Inflammation Discovery and Translational Areas [see article, page 8]. This past April, HSS received a $5.6 million grant from The Tow Foundation to establish the Hospital for Special Surgery Genomics Center. The new Center, under the leadership of Dr. Lionel Ivashkiv, is applying genomic approaches to study rheumatoid arthritis and systemic lupus erythematosus with the aim of developing more effective therapies. Specifically, the Center’s investigators will incorporate genomics to understand the regulation and function of disease-associated genes; determine how disease-associated genetic variants contribute to disease; identify new genes associated with autoimmune diseases; and employ this new knowledge to develop more effective and personalized treatment of diseases. The Genomics Center will focus on several aspects of research, including epigenetics, which looks at how environmental factors regulate genes involved in autoimmune disease. This knowledge would represent a new way to drive therapy. Division of Rheumatology

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The large volume of patients treated at the Hospital has enabled HSS clinicians and researchers to develop nearly 50 patient registries with an enrollment of over 84,000 patients, in concert with repositories that store DNA linked with clinical information. In the Division of Rheumatology, these registries, some of which have a national and international reach, are focused on lupus, antiphospholipid syndrome, pediatric vasculitis, childhood arthritis, early systemic sclerosis, and myositis, are an important resource to clinicians and scientists alike, providing a significant evidence base for new treatments and clinical outcomes. The information afforded by these registries not only furthers our ability to provide better care to our own patients, but also raises the standards of care in the national and international medical arenas through the sharing of information in peer-reviewed publications and presentations at society meetings.

The Genomics Center will focus on several aspects of research, including epigenetics, which looks at how environmental factors regulate genes involved in autoimmune disease.

Fostering Careers in Rheumatology Each year, our three-year Rheumatology Fellowship Program accepts three fellows to train under a nationally and internationally recognized faculty. Their comprehensive training extends from the clinics and laboratories of HSS to the inpatient units of NewYork-Presbyterian/Weill Cornell Medical Center and Memorial Sloan-Kettering Cancer Center and the research programs of The Rockefeller University. Our current group of 10 rheumatology fellows and five pediatric rheumatology fellows obtains in-depth training in the diagnosis and management of autoimmune, inflammatory, and musculoskeletal disorders, and at the same time pursues a basic or clinical research project. A National Institutes of Health T32 Rheumatology Research Training Grant continues to provide support to HSS fellows interested in pursuing a career in rheumatic disease research. The Hospital recently created a Clinician Scientist Program, funded by the Kellen Foundation, to mentor and support early career clinical faculty at HSS who are committed to careers as clinician scientists. Rheumatologist Jessica K. Gordon, MD, MSc, who completed her fellowship training at HSS in 2008, was one of six selected for the Anna-Maria and Stephen Kellen PhysicianScientist Career Development Award through a competitive and rigorous review process. The award is presented to scientists who have been identified as future leaders of research in their respective fields and have demonstrated well-defined research activities integrated with clinical responsibilities. A member of the Scleroderma, Vasculitis, and Myositis Center, Dr. Gordon is being mentored by Robert F. Spiera, MD, Director of our Scleroderma, Vasculitis, and Myositis Center of Excellence. 3

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Continuing Our Mission of Excellence Our patients benefit not only from the expertise of the clinicians and health professionals of a world-renowned specialty hospital, but also from the commitment of Hospital for Special Surgery to providing safe and exceptional care – using evidence-based practices and quality indicators – in all of its service areas. In 2012, The Joint Commission acknowledged the Hospital as one of its Top Performers on Key Quality Measures.® HSS was the only Manhattan-based hospital among the 620 hospitals singled out for achieving an exemplary level of accountability measure performance. In addition, patient satisfaction with Hospital for Special Surgery is consistently ranked in the 99th percentile by Press Ganey.

Patient Satisfaction: Inpatient Musculoskeletal Surgery and Perioperative Medical Care Q1 2011 - Q2 2013 Overall Rating of Care Provided by HSS HSS has ranked in the 99th percentile for the past 12 consecutive quarters. Likelihood of Patients to Recommend HSS HSS has been in the 99th percentile for 20 consecutive quarters.

In the 2013 Annual Report of the Division of Rheumatology, we provide a look at two major initiatives in research that we believe have the potential to change the way we think about and manage inflammatory and autoimmune diseases. We also introduce you to four members of our faculty who provide their perspective on treating patients with some of the more challenging medical circumstances that bring them to HSS for rheumatology care, and the vital role a member of our faculty is playing in the overall care of orthopaedic surgical patients.

Mary (Peggy) K. Crow, MD, MACR Physician-in-Chief and Chair, Division of Rheumatology Benjamin M. Rosen Chair in Immunology and Inflammation Research Hospital for Special Surgery Joseph P. Routh Professor of Rheumatic Diseases in Medicine Weill Cornell Medical College

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Rheum to Heal: A New Narrative Journal by and for People Living with Rheumatic Conditions and Their Physicians and Caregivers Rheumatic diseases don’t play by the rules. The conditions can be debilitating, often chronic, and frequently penetrate the very foundation of patients’ lives. These diseases can dismantle patients’ days and nights in profound ways no textbook can fully cover. In 2013, Hospital for Special Surgery launched Rheum to Heal: Stories of Health and Humanity, a new, online narrative journal by and for people living with rheumatic conditions and the medical professionals who care for them. The emotional impact of chronic rheumatic diseases, once creatively expressed, has the ability to unite and heal. Using the power of words and images, Rheum to Heal hopes to transform all who share them. Rheum to Heal is published and distributed through a free online subscription. Each issue features poetry, prose, artwork, and photography on, or related to, themes of health, healing, challenges of navigating illness, and mind, body, and/or self-transformation. The journal welcomes all forms of creative expression from patients with arthritis, autoimmune diseases, painful joint disorders, and osteoporosis, as well as doctors, clinicians, and health professionals – practicing or retired – in the field of rheumatology and other medical professionals involved with helping those who have rheumatic conditions. In sponsoring this narrative medicine journal, our hope is to build a sense of community among people with similar health struggles and reduce the sense of isolation that often accompanies chronic illness. We want to create a platform to showcase and share the healing power of their voices and stories. You can access Rheum to Heal at www.hss.edu/rheumtoheal/.

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Perioperative Medicine: A Model Program Preparing Patients for Orthopaedic Surgery

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hile the co-management by a surgeon and a medical physician of a patient undergoing orthopaedic surgery has long been practiced at Hospital for Special Surgery, under the direction of Linda A. Russell, MD, this patient care model has developed into a comprehensive and established program gaining national recognition. Appointed Director of the Division of Perioperative Medicine in 2011, Dr. Russell today oversees 11 internists and hospitalists who, along with eight rheumatologists with active perioperative medical practices, collaborate with HSS surgeons to assure optimal preparation and postoperative management of patients undergoing orthopaedic surgery. Dr. Russell and her colleagues have developed several new guidelines for laboratory, imaging, and consultative assessment of patients scheduled for inpatient surgery based on current evidence-based literature. “Our goal is to optimize the health of the patient before, during, and after surgery,” says Dr. Russell. “Our focus over the last few years has been to look at evidence-based medicine, systematize the way that we take care of patients, and put protocols in place so that they are implemented across the board.” Dr. Russell notes that a number of patients coming to HSS for hip and knee replacement surgery are older with comorbidities and require a thorough medical evaluation in preparation for surgery, particularly if they have hypertension, cardiovascular disease, or diabetes – a recent major initiative for the perioperative team. “Research shows that the more a patient’s diabetes is controlled, the better the surgical outcome, with less infections and fewer cardiovascular complications,” says Dr. Russell. “So, a year and a

Dr. Florence Yu reviews the medical history of Thomas Gorman, who is scheduled for knee replacement surgery at HSS, and performs a thorough clinical exam to make sure he can be cleared for his orthopaedic procedure.

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Dr. Linda A. Russell

half ago we decided that everyone who has diabetes who is going to have surgery here must have a hemoglobin A1c blood test, which tells us how well their diabetes has been controlled for the past three months. We now have very specific recommendations – if the number is too high, surgery will be postponed until the diabetes is under better control. If the result is not quite that high, but the diabetes is still not perfectly controlled, we have a strategy to try to improve that; however, the patient is medically cleared to have surgery. And then there are the patients who have their diabetes well controlled. We feel good about them going into the operating room.” A diabetes nurse practitioner has joined the perioperative team to follow any patient using an insulin pump. “We need to be able to advise if medication should be stopped or continued, and if pumps should remain on or be turned off during surgery,” says Dr. Russell. Notes Florence Yu, MD, an internist at HSS and a member of the perioperative team, “Our role is to screen these patients for surgery. We have very strict guidelines as to what we consider is safe for a person who has an elective procedure. We want to know all of their medical risk factors so that when they come in for surgery we’re fully prepared for whatever we may encounter and ensure that they do well after surgery.” Dr. Yu appreciates the opportunity available at HSS to refer a patient to a rheumatologist, if necessary, prior to surgery. “Many people who require joint surgery have rheumatologic disorders,” she says. “If I am evaluating a patient with advanced rheumatoid arthritis, for example, I want a rheumatologist to determine if the medication has to be optimized. We want to make sure that everything is well controlled before a patient goes in for surgery.” “Indeed, many patients who can be helped by orthopaedic surgery have underlying inflammatory rheumatologic problems,” adds Dr. Russell. “The rheumatologist is the perfect person to decide when the medications should be stopped before surgery, when it’s safe to resume them, and how to manage these patients if they have a flare of their disease around the time of surgery.”

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CATCH-US: The Canadian Early Arthritis Cohort Study Comes to America

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hen rheumatologist Vivian P. Bykerk, MD, joined Hospital for Special Surgery two years ago, she brought with her a wealth of knowledge and experience as lead investigator of the Canadian early ArThritis CoHort (CATCH), an ongoing multicenter research project in Canada that has been collecting information on patients with early inflammatory arthritis. At the 2013 annual meeting of the American College of Rheumatology, Dr. Bykerk presented findings of this research that impart a clear message: Delaying treatment for rheumatoid arthritis could greatly increase the likelihood that patients will suffer worse disability two years out.

“CATCH-US will facilitate collaborative research and basic science in new onset inflammatory arthritis, with a particular interest in projects that translate into better outcomes in clinical practice.” — Dr. Vivian P. Bykerk CATCH in Canada CATCH encompasses a network of 19 clinical sites throughout Canada, located in teaching hospitals, community-based hospitals, and clinics. Its main goal is to learn more about the impact of early arthritis and promote the benefits of early arthritis treatment. Since its inception seven years ago, the project has collected data on 1,800 patients. “When we first started CATCH, our core group was interested in how our patients with early arthritis actually do in terms of clinical outcomes and if we could predict their outcomes based on certain characteristics,” says Dr. Bykerk, who is today the Director of the Inflammatory Arthritis Center at Hospital for Special Surgery. “It was, primarily, a best outcomes mission. Along with that, we wanted to educate patients to the importance of early diagnosis and prevent them from developing deformity, disability, and dysfunction.” The research has produced and continues to deliver abundant and important data on outcomes of patients with early RA – defined as having symptoms of joint pain and swelling for one year or less – including patient-reported measures, medication usage, physical findings, and changes noted in imaging studies. “We have shown, for example, that people who have been treated in larger sites tended to have higher rates of remission and are generally prescribed a more intensive treatment regimen,” notes Dr. Bykerk. Most recently, Dr. Bykerk and her Canadian colleagues reported on the impact of low disease activity at six months on the level of

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Dr. Vivian P. Bykerk has participated in the design of randomized controlled trials and long-term observational studies evaluating real world remission rates in RA and their predictors, therapeutic care gaps, and predictive diagnostic algorithms. Since 2006, she has served as the principal investigator of the CATCH study in Canada and continues her research as principal investigator of CATCH-US, a parallel study in the United States.

disability at two years, using the health assessment questionnaire disability index. This self-reported survey is a dominant instrument used in assessing RA, gauging the difficulty a patient has in performing basic activities, such as walking, bathing, eating, and dressing. The study showed that achieving low disease activity at six months was a significant, independent predictor of lower disability at two years. “Patients who were able to achieve disease control sooner had better function than the ones who did not,” says Dr. Bykerk. “As expected, age and sex were also predictive of disability.”

CATCH in the U.S. CATCH was the first time that a multicenter study of early arthritis had been undertaken in Canada. So when Dr. Bykerk relocated to New York City and Hospital for Special Surgery, it was a natural progression for her to introduce a parallel study in the United States. In the development of CATCH-US, Dr. Bykerk and her colleagues are using similar data capture mechanisms toward the same goal: to understand best practices that can be implemented more widely to enable patients with new onset RA to achieve remission.

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The new American-based initiative, which will begin in early 2014, includes a collaboration of investigators in eight major medical center sites spanning the East and West Coasts. “We do know that many patients with new onset inflammatory arthritis come to medical attention too late, and a substantial number of patients continues to experience poor outcomes,” notes Dr. Bykerk. Good outcomes are further impeded in that not all patients receive optimal treatment strategies such as methotrexate, combination disease-modifying antirheumatic drugs, or biologics. The CATCH and CATCH-US studies aim to identify early predictors of poor prognosis that will more accurately rationalize the early use of optimal treatment strategies and track their tolerability. Baseline Characteristics of CATCH-US Study Participants Characteristic

Value

Age (years), mean ± SD

52.2 ± 15.8

Female sex, no. (%)

815 (71.2)

Duration of symptoms (months) ± SD (Range)

6.3 ± 3.7

HAQ score, mean ± SD

0.94 ± 0.72

DAS28 score, mean ± SD

4.53 ± 1.99

RF positive, no. (%)

636 (57.1)

Anti-CCP positive, no. (%)

424 (60.0)

Tender joint count (TJC28) ± SD

8.19 ± 6.82

Swollen joint count (SJC28) ± SD

7.42 ± 6.28

“Ultimately, we would like to personalize care for patients who have all of the predictors – clinical, biochemical, and even genetic – for disease that will have a poor prognosis and develop a tool that physicians and patients can use to understand the likely trajectory of their disease and their best first choices of treatment,” says Dr. Bykerk. “These patients should have a different initial treatment strategy than a patient who has predictors for being a good responder to usual therapies.” According to Dr. Bykerk, the greatest challenge is the patient who comes in with what appears to be minimal disease. “In these cases, even if their symptoms are mild, we don’t always know if their disease will imminently worsen, and the trend is to undertreat these people,” says Dr. Bykerk. “We want to understand how can we give a person the best treatment option to achieve a sustained drug-free remission when he or she presents with onset of joint inflammation (synovitis) that accompanies RA. Unfortunately, I have seen too many people delay effective treatment approaches and come back a year later very disappointed, often with joint damage that could have been prevented. The longer inflammation remains active in the joints, the more likely joint damage will occur. Once damage has happened it can’t be reversed and will impact how a person with RA functions down the road.” Division of Rheumatology

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Inclusion Criteria CATCH-US STUDY PARTICIPANTS 1. Age > 16 2. Symptoms < 12 months 3. ≥ 2 effused joints or 1 swollen metacarpal phalangeal/ proximal interphalangeal 4. P lus ≥ 1 of: • Rheumatoid factor positive • Positive anti-citrullinated peptide antibody • Morning stiffness ≥ 45 minutes • Response to NSAID • Positive metatarsophalangeal joint squeeze test

CATCH-US currently has several studies and sub-studies in development or underway in the area of prognosis and prediction. These include identifying: • b iomarkers that can determine prognosis in treatment naïve patients • p redictors of the development of established RA in patients presenting with undifferentiated arthritis • biomarkers that predict erosive arthritis in sero-negative RA Sub-studies are also being devised that will focus on determining if ultrasound can identify RA earlier, if patient flares can be identified and managed early, and understanding the impact of flares on treatment needs, radiographic progression, and function. “We believe there is a window in which people have a much better chance of getting rheumatoid arthritis under good control, often with less intense therapy, and the window may well be within the first three months of developing joint inflammation,” says Dr. Bykerk. “I believe arthritis specialists should meet with their patients often in the early phases of RA so that they can assess how they are responding to treatment. The longer patients wait, the more likely it is that they will need more intense therapy to achieve the same control of joint inflammation.” Reference Articles Barnabe C, Xiong J, Pope JE, Boire G, Hitchon C, Haraoui B, Carter Thorne J, Keystone EC, Bykerk VP, Canadian early ArThritis CoHort (CATCH) Study Investigators. Factors associated with time to diagnosis in early rheumatoid arthritis. Rheumatology International. 2013 Aug 30. [Epub ahead of print] Boyd TA, Bonner A, Thorne C, Boire G, Hitchon C, Haraoui BP, Keystone EC, Bykerk VP, Pope JE, and the CATCH Investigators. The relationship between function and disease activity as measured by HAQ and DAS28 varies over time and by rheumatoid factor status in early inflammatory arthritis (EIA). Results from the CATCH Cohort. The Open Rheumatology Journal. 2013 Aug 28;7:58-63. Barra L, Bykerk VP, Pope JE, Haraoui BP, Hitchon CA, Thorne JC, Keystone EC, Boire G, and the CATCH Investigators. Anticitrullinated protein antibodies and rheumatoid factor fluctuate in early inflammatory arthritis and do not predict clinical outcomes. Journal of Rheumatology. 2013 Aug;40(8):1259-67.

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From Drug Targets to New Therapies for Inflammatory and Autoimmune Diseases

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aving spent his early career in research and development in the pharmaceutical industry, Franck J. Barrat, PhD, is now providing an important perspective to the academic research environment of Hospital for Special Surgery. A talented and experienced researcher who has distinguished himself in drug discovery – from target identification to the filing of Investigational New Drug Applications with the FDA and proof-of-mechanism clinical studies – Dr. Barrat recently joined HSS from Roche, where he was a Distinguished Scientist in the company’s Inflammation Discovery and Translational Areas. Previously, Dr. Barrat served as Senior Research Fellow and Project Leader of the Autoimmunity Program of Dynavax Technologies. This experience, coupled with his PhD in immunology from the University of Paris, a master’s degree in immunology from the Pasteur Institute, and a master’s degree in pharmacology from the University of Nice, guides his current research at HSS in the identification of drug targets for the development of new therapies for inflammatory and autoimmune diseases. “During my PhD training, I worked with patients who had immune deficiencies pursuing mechanistic studies in human inflammation,” says Dr. Barrat. “We had direct access to the patients because the director of the research lab was also the director of the clinical department. I then decided to do my postdoctoral fellowship in mouse studies, looking at key signals in the induction of regulatory T cells.” Leveraging his training in both human and animal studies, Dr. Barrat, while at Dynavax, went on to discover and develop DV1179, a bifunctional Monoclonal antibodies targeting inhibitor of the toll-like mouse toll-like receptor 9 receptors 7 and 9, taking the drug from early discovery work to clinical trials in patients with systemic lupus erythematosus (SLE). “The strength of working in industry is that you can have an idea of how to make a drug and then see its development all the way through to its testing in clinical studies,” explains Dr. Barrat. “That’s very powerful, and there’s a lot of drive, energy, and motivation to get new drugs to patients. However, as a scientist in the industry setting, you’re removed from what is occurring during the clinical studies. I had trained in an environment where scientists and clinicians worked side by side fairly often. I wanted to return to a setting where I could directly interact with the people who see the patients. So I left industry to work in academia.” 8

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Applying Industry Know-How to an Academic Medical Setting Coming into the research environment of HSS, which draws its strength from collaborations among basic scientists and clinicians, Dr. Barrat is building on his previous work in understanding nucleic acid recognition in autoimmunity and the potential clinical benefit of interfering with toll-like receptor (TLR) signaling in human diseases. Nucleic acids, which include DNA and RNA, are among the most important biological molecules, functioning in encoding, transmitting, and expressing genetic information.

“ I find it particularly fascinating because nucleic acid responses have not changed since the age of dinosaurs. There have been millions of years of evolution to craft immune responses to these molecules.” — Dr. Franck J. Barrat “I think the way to push what I’m doing to the next level is to look at nucleic acid responses in the context of actual patients,” says Dr. Barrat. “There are actually multiple layers of receptors, pathways, and cell types that are focused on recognition of nucleic acids. I find it particularly fascinating because nucleic acids have not changed since the age of dinosaurs. There have been millions of years of evolution to craft immune responses to these molecules. What’s become apparent in the last 15 years or so is that in some situations toll-like receptors can become misguided, causing the immune system to create a response to its own nucleic acids. This is what drives autoimmunity. Our goal is to identify various mechanisms that can interfere with these receptors and prevent self nucleic acid recognition from occurring.” Using SLE as an example, Dr. Barrat explains that patients with lupus all have autoantibodies to nucleic acids. “They actually make antibodies to double-stranded DNA,” he says. “One of the classic tests for lupus is to see if a patient has antibodies to their own double-stranded DNA, to ribonucleoprotein, or to Smith antigens, which are proteins bound to RNA.” r. Barrat has already made great headway in this area, having D previously developed inhibitors of the toll-like receptors 7 and 9 that he and his colleagues at Dynavax believed would be the most relevant for lupus. The researchers demonstrated, in vitro and in vivo, that stimulation of plasmacytoid dendritic cells (pDCs) through TLR7 and 9 can account for the reduced activity of glucocorticoids to inhibit the interferon pathway in SLE patients

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Having established a strong rationale linking the activation of TLR7 and 9 in lupus, with novel inhibitors now being tested in a clinical trial, Dr. Barrat and his team have turned their attention to TLR8. “There is now considerable evidence that selfrecognition through toll-like receptors can occur and can contribute significantly to sterile inflammation and autoimmunity,” notes Dr. Barrat. “TLR8 signaling induces important inflammatory cytokines, such as interleukin-6 and tumor necrosis factor, and TLR8 is expressed by multiple cell types involved in inflammatory diseases.” However, the lack of useful mouse models has proven to be a major impediment to the study of TLR8 biology. To address this, Dr. Barrat’s lab is developing new tools to study Interleukin-6, shown here in this receptor in patients with its crystal structure, is an autoimmune diseases, but also inflammatory cytokine in vivo using novel approaches induced by TLR8. to circumvent the lack of function in mouse models. In the HSS laboratory of Dr. Franck J. Barrat, studies are underway into the function and role of human plasmacytoid dendritic cells in immunity and TLR8 in inflammation that are expected to aid in the development of novel therapies for inflammatory and autoimmune disease.

and in two lupus-prone mouse strains. Their findings uncovered a new role for self nucleic acid recognition by toll-like receptors and suggest that inhibitors of TLR7 and 9 signaling could prove to be effective corticosteroid-sparing drugs. These inhibitors are now in Phase 1 and 2 clinical studies for lupus patients. The role of neutrophils in the pathogenesis of SLE has also been under investigation by Dr. Barrat. In a study published in Science Translational Medicine, Dr. Barrat and collaborators demonstrated that mature SLE neutrophils are primed in vivo by type I interferon and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs). “These SLE NETs activate pDCs to produce high levels of interferon alpha in a DNA- and TLR9-dependent manner,” explains Dr. Barrat. “This study exposed an unanticipated role for neutrophils in SLE pathogenesis, identifying a novel link between nucleic acid recognizing antibodies and type I interferon production in this disease.”

Studying TLRs and pDCs in Autoimmunity In his lab at HSS, Dr. Barrat continues to explore both human and mouse approaches focusing on the function and roles of toll-like receptors 7, 8, and 9 in inflammation. According to Dr. Barrat, the innate immune system faces the same fundamental challenge as the adaptive immune system – distinguishing self- from non-self-antigens.

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Dr. Barrat’s lab is also investigating human pDCs, which represent a link between innate and adaptive immunity. “These cells can either produce massive amounts of type I interferon and participate in anti-viral responses, or they can mature to become effective antigen presenting cells that activate T cells,” says Dr. Barrat. “We have shown that these two functions are induced following TLR signaling and can be differentially affected by the cytokine milieu and by the signaling molecules involved in the TLR pathway.” Having also described that endosomal location – not physical form or valency – is the primary determinant of the signaling pathway utilized by TLR9 in human pDC, Dr. Barrat and his team are now looking at its unique role in immunity and as the basis of many potential clinical applications, in particular, for the treatment of cancer, allergies, and viral infections. Reference Articles Garcia-Romo GS, Caielli S, Vega B, Connolly J, Allantaz F, Xu Z, Punaro M, Baisch J, Guiducci C, Coffman RL, Barrat FJ, Banchereau J, Pascual V. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Science Translational Medicine. 2011 Mar 9;3(73):73ra20. Guiducci C, Gong M, Xu Z, Gill M, Chaussabel D, Meeker T, Chan JH, Wright T, Punaro M, Bolland S, Soumelis V, Banchereau J, Coffman RL, Pascual V, Barrat FJ. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature. 2010 Jun 17;465(7300):937-41. Guiducci C, Tripodo C, Gong M, Sangaletti S, Colombo MP, Coffman RL, Barrat FJ. Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9. The Journal of Experimental Medicine. 2010 Dec 20;207(13):2931-42.

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Disease-Focused Centers: Models of Excellence In 2010, Mary K. Crow, MD, MACR, Chair of the Division of Rheumatology, created a “Centers of Excellence” framework to enhance the coordination of patient care, facilitate training and education programs, and to advance research initiatives focused on specific autoimmune and inflammatory disorders. In particular, these centers serve to stimulate the dialogue among the Hospital’s clinicians and scientists, who routinely collaborate to identify clinical challenges that can be explored and explained at the most basic level with a goal toward developing better therapeutic options for patients.

Bone Health and Osteoporosis Center of Excellence

Pediatric Rheumatology Center of Excellence

Linda A. Russell, MD, Director

Our pediatric rheumatology program has made great strides in the care of children with rheumatic diseases and related conditions, continuing to identify new and effective therapeutic treatments. Medications that are used by adult rheumatologists are now prescribed, as appropriate, by our experienced pediatric rheumatologists with excellent outcomes. With new biologic therapies, many of them tested at HSS, along with physical therapy, children are regaining normal function and quality of life.

Basic scientists and medical and orthopaedic specialists have come together in the Bone Health and Osteoporosis Center to focus on the prevention and treatment of osteoporosis, Paget’s disease, and related bone disorders; preserving bone quality; and promoting bone healing. HSS physicians and nurses have developed a new clinical pathway to better identify those with bone disease and those at risk in order to map the course for proper intervention. The pathway is currently being used in candidates for spinal fusion surgery to optimize their bone health prior to and following surgery.

Thomas J.A. Lehman, MD, Director

Scleroderma, Vasculitis, and Myositis Center of Excellence

Inflammatory Arthritis Center of Excellence

Robert F. Spiera, MD, Director

Vivian P. Bykerk, MD, Director

Scleroderma is a major focus of basic research studies and clinical investigations at HSS. The Center’s physician scientists continue to collect clinical information and biological materials on patients with scleroderma to learn more about the pathophysiology of the disease. They have been involved in a number of clinical trials to define better therapies for this population. Programs continue to grow in vasculitis following the Hospital’s participation in the landmark study of rituximab therapy, and in inflammatory myopathies, with a goal to increasing understanding of these rare diseases.

The Inflammatory Arthritis Center brings together the physicians who treat patients with rheumatoid arthritis, psoriatic arthritis, spondyloarthropathies, and other inflammatory disorders. Most recently, the Center launched CATCH-US, an HSS-based, national multicenter program to study patients with new onset arthritis and develop approaches to improving diagnosis, treatment, and outcomes. In addition, the Hospital’s rheumatologists and orthopaedic surgeons have a number of research projects underway to explore and improve perioperative outcomes of patients with rheumatic disease.

Osteoarthritis Center of Excellence Osteoarthritis (OA) is the focus of national attention, with physicians, scientists, rehabilitation specialists, and educators pooling their resources and expertise to tackle this growing concern. At HSS, OA is a top clinical priority, with multiple disciplines mobilizing to focus on advancing non-surgical and surgical options for patients. Since launching its OA Initiative five years ago, the Hospital has developed numerous multidisciplinary research activities and clinical trials to help address the broad-ranging challenges of OA, including strategies to prevent, repair, regenerate, or replace injured and deteriorating cartilage. More than 350 clinicians, clinical investigators, and basic scientists across the Division of Rheumatology, the Department of Orthopaedic Surgery, and the Research Division at HSS are addressing OA on some level.

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Lupus and Antiphospholipid Syndrome Center of Excellence Jane E. Salmon, MD, Director Hospital for Special Surgery is home to a renowned team of clinicians and scientists who are seeking to address the many challenges of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), investigating the myriad manifestations of these diseases at the molecular level and bringing their findings to bear on managing SLE and APS and their complications in patients. Two decades ago, the Hospital became the nation’s first National Institutes of Healthsponsored Specialized Center of Research in SLE, and since then has made many contributions to identifying immune system triggers, understanding the role of interferon and other immune system mediators, and uncovering causes of disease activity and flares.

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Point of View: Our Experts’ Perspectives on Complex Cases Antiphospholipid Syndrome Doruk Erkan, MD, MPHxx

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Guiding the Management of Severe APS A consultation was requested on a 19-year-old male with SLE, severe APS, and extensive arterial thrombosis that mainly affects his right lower extremity. Last spring, due to his worsening thrombosis, the patient’s anticoagulant therapy was modified, and he received plasmapheresis, IVIG, and pulse steroids with no response. With basically no blood flow in his right leg, the patient had a mid-metatarsal amputation and now a below-the-knee amputation is planned. Currently, the patient is receiving low-molecular-weight heparin and methylprednisolone. The patient’s rheumatologist is seeking guidance on other treatments I might advise pre- and post-surgery, as well as my recommendation on long-term management. It’s not unusual for Doruk Erkan, MD, MPH, Clinical Co-Director of the Mary Kirkland Center for Lupus Care and Associate Physician-Scientist of the Barbara Volcker Center for Women and Rheumatic Diseases at Hospital for Special Surgery, to be consulted on such medically complex circumstances involving a patient with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). A distinguished researcher in both SLE and APS, Dr. Erkan chairs and was one of the founders, along with Michael D. Lockshin, MD, Director of the Barbara Volcker Center for Women and Rheumatic Diseases, of APS ACTION (Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking). APS ACTION is an international collaborative – now with 25 centers – that designs and conducts large-scale multicenter and multidisciplinary clinical research of patients with persistent and clinically significant antiphospholipid antibodies (aPL). “The major goal of APS ACTION is developing new therapies for aPL-positive patients,” says Dr. Erkan, who also serves as the principal investigator for the organization’s two main clinical research studies. One study, for instance, an international registry and respository, will recruit 2,000 patients with a 10-year follow-up. Dr. Erkan, who was recently selected to chair the 15th International Congress on Antiphospholipid Antibodies that will take place in September 2016 in Istanbul, Turkey, also co-authored the most current textbook available on antiphospholipid syndrome covering all of the discussions of the 13th International Congress held in September 2010. Antiphospholipid antibody positive patients may present with a wide spectrum of clinical manifestations ranging from asymptomatic individuals to those with pregnancy complications, blood clots, other non-thrombotic problems such as low platelet counts and, the most severe form, catastrophic APS. Division of Rheumatology

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Dr. Doruk Erkan

“Catastrophic APS is a condition where patients have multiple clots, commonly affecting the small vessels,” notes Dr. Erkan. “The disease is associated with 30 to 50 percent mortality despite optimal treatment. Many physicians – and families – will reach out to me for difficult-to-manage manifestations of APS, including catastrophic APS, or to help determine a patient’s eligibility for one of the several clinical trials that are ongoing in APS. For example, I have an e-mail now from a doctor about a patient with APS who has developed simultaneous pulmonary emboli with rectal bleeding, asking what my approach would be.” According to Dr. Erkan, there is both over-diagnosis and underdiagnosis of APS, and many of the phone calls or referrals he receives are also about whether a clinical manifestation could be related to antiphospholipid antibodies. In addition, as a member of the Barbara Volcker Center for Women and Rheumatic Diseases, Dr. Erkan is commonly consulted for patients with no established diagnosis despite long-standing symptoms suggestive of systemic autoimmune diseases. “There are clear-cut rheumatologic diseases and then there are systemic autoimmune diseases that are not well-defined; diagnosis and the management of these more ambiguous presentations can be really challenging.” Reference Articles Barbhaiya M, Erkan D. Top 10 clinical research developments in antiphospholipid syndrome. Current Rheumatology Reports. 2013 Oct;15(10):367. Sullivan TR. ACR/ARHP Annual Meeting 2012: Tips to diagnose and treat catastrophic antiphospholipid syndrome (CAPS). The Rheumatologist. April 2013 [An interview with Dr. Doruk Erkan] For More Information www.apsaction.org • www.apsistanbul2016.org

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Lupus and Pregnancy Lisa R. Sammaritano, MD Achieving Successful Pregnancies Case 1 A 35-year-old patient with significant lupus and kidney disease has been eager to conceive for five years. The medication necessary to treat her lupus nephritis (mycopheonolate mofetil) is not safe to take during pregnancy. She was switched to a pregnancy-safe medicine (azathioprine) but it did not control her lupus the way the first medicine had and she suffered a major flare of her kidney disease. The patient’s plans for pregnancy were put on hold while she returned to the first medicine for another two years of treatment to enable her to go into remission once again. She was then changed to a medication (tacrolimus) not commonly used for lupus nephritis, but rather by kidney doctors for transplant patients to prevent rejection. We proceeded with “watchful waiting” for another six months. The new medication, which is safe for pregnancy, continued to control her kidney disease and we gave her the go-ahead to try to get pregnant. She is now at 12 weeks and we continue to follow her as her pregnancy progresses. Case 2 A 39-year-old lupus patient wanted to proceed with plans to freeze her eggs in the hope of having biological children one day. Her rheumatologist felt very uncomfortable with the patient’s decision because she has mild lupus, as well as antiphospholipid antibodies, which raise concerns for flare of disease and risk of blood clots in the setting of fertility treatment. He referred the patient to me and I consulted with the fertility doctor on her evaluation. With the fertility specialists, we worked out a protocol for her to go ahead with the cryopreservation process. We treated her with blood thinning medication to reduce her risk of having a blood clot because of the antiphospholipid antibodies. We also gave her a low dose of prednisone to try to minimize her risk of having a lupus flare. All of this involved a tremendous amount of back and forth, as well as a great deal of counseling for an understandably anxious patient.

Rheumatologist Lisa R. Sammaritano, MD, receives many referrals for either consultation or for the care of patients with lupus and other autoimmune diseases who are considering pregnancy. Since completing her rheumatology fellowship in 1991 at Hospital for Special Surgery, Dr. Sammaritano has developed a clinical practice with particular expertise in systemic lupus erythematosus, antiphospholipid antibody syndrome, and related reproductive issues. She trained and now works side by side with many of the Hospital’s physician scientists who

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were among the first to study pregnancy complications and enable women with lupus to go on to have safe and healthy births. She follows many of these women during their pregnancy in coordination with their primary rheumatologist, who resumes their care after the immediate postpartum period. Dr. Sammaritano advises that Dr. Lisa R. Sammaritano if a woman of childbearing age has lupus, it is important for the rheumatologist to be involved before the patient becomes pregnant. “For patients with any underlying illness, but especially in autoimmune disease, you really need to plan ahead of time because there are many issues to address,” says Dr. Sammaritano. “For example, medications given for lupus can have adverse effects during pregnancy and some, in fact, will need to be discontinued up to three months before the patient becomes pregnant. The next challenge is trying to assess how risky a pregnancy might be for a given patient, taking into account the nature of the diagnosis, how active the disease is, and a number of other factors.” Over the past 30 years there have been many studies looking at the risks of pregnancy and, more importantly, how to define the risk for a given individual. “What I try to do is use what I know about lupus pregnancy risk – whether it’s risk of a flare, risk to the outcome of the pregnancy, or another issue – and counsel the patient in terms of her individual situation and medical history,” explains Dr. Sammaritano. “Just as lupus is puzzling and unpredictable, it’s also incredibly heterogeneous. We may have lupus patients with a mild rash and occasional joint pain at one end of the spectrum. At the other end is the patient who is extremely ill and has been in the ICU. Such patients are going to have very different outlooks when it comes to considering pregnancy.” Dr. Sammaritano will first determine if the disease has affected the patients in such a way that it would not be safe to undertake a pregnancy. “They may have severe renal inflammation and insufficiency, significant cardiac or valvular disease, or pulmonary hypertension and severe lung disease that make it too dangerous for them to go through a pregnancy,” continues Dr. Sammaritano. “If a patient has active lupus, that is a bad time to consider pregnancy. We encourage patients to have six months of quiet disease and then we’ll look at various laboratory values, including antiphospholipid antibodies, which might increase the risk for having a bad pregnancy outcome such as pregnancy loss with a miscarriage or a stillbirth, severe preeclampsia, or early delivery with a small or premature baby. We also need to evaluate the medications that the patient is taking to make sure they won’t have an adverse effect on the developing fetus.” Hospital for Special Surgery

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Dr. Sammaritano emphasizes the importance of a team approach. “One of my patients calls me her quarterback. Since these diseases so often involve many different organ systems, rheumatologists need to have the broad view and coordinate and consult closely with all disciplines involved in the care of the mother and the fetus: the obstetrician who is focused on the baby; the nephrologist whose attention is on the kidney; the hematologist who monitors blood levels. Case 1 is an example of how involved the planning can be. However, if you do the planning properly – even when it’s lengthy – based on our experience and clinical studies, you can achieve a successful pregnancy outcome.”

“ Since these diseases often involve many different organ systems, rheumatologists need to have the broad view and coordinate and consult closely with all disciplines involved in the care of the mother and the fetus.” — Dr. Lisa R. Sammaritano Patients who are advised to wait to become pregnant until their lupus is quiet may go on to develop age-related fertility issues. Frequently, patients are referred to Dr. Sammaritano for a second opinion about fertility therapy. “I think that some rheumatologists don’t always feel that they have enough knowledge of pregnancy issues to do effective counseling,” notes Dr. Sammaritano. “However, it really is a very important part of care when a lupus patient is considering becoming pregnant or undergoing a fertility-related procedure. I spend a lot of time educating patients and their partners, explaining the potential risks to the mother and developing fetus. I feel comfortable doing that; some rheumatologists may not.” Dr. Sammaritano works closely with fertility specialists in the renowned Center for Reproductive Medicine of Weill Cornell Medical College. When their faculty members have a patient present to them who might have a rheumatologic disease, they ask her to consult. “Some of the fertility therapies, such as IVF and ovarian stimulation protocols, trigger the same physiologic changes that can occur during pregnancy,” says Dr. Sammaritano. “There’s a concern that these might also precipitate a lupus flare. So the Center’s physicians rely on me to clear the patient to undergo the ovarian stimulation involved in in vitro fertilization. Similarly, if my patients are having fertility issues, I look to those colleagues for their expertise. It’s very rewarding to be able to help someone – another physician’s patient or my own – through the pregnancy and achieve a positive outcome.”

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Inflammatory Arthritis Vivian P. Bykerk, MDxxxx Addressing Concerns of a Patient with RA A young woman with worsening rheumatoid arthritis recently came to see me. It was a third opinion on how to best manage her RA, which had started very mildly and then accelerated over the last year. She was on methotrexate, which is our usual first-line of treatment, and its dose was being escalated very slowly. She also had a lot of fears about her disease. I approached her first by asking her what she is afraid of, what she thinks is going to happen, what she expects from the medication, what she’s read about, and what did her previous doctors tell her. You really have to understand the patient’s perspective in order to help them play a role in managing their disease effectively.

Vivian P. Bykerk, MD, has made it her life’s mission to know everything there is to know about the best clinical management of RA. As one of the founders and principal investigators in CATCH – first in Canada and now in the U.S. – Dr. Bykerk has established a far-reaching reputation for her work in diagnosing, managing, and enhancing the overall quality of care for patients with early inflammatory arthritis [see page 6].

Dr. Vivian P. Bykerk

“Frequently, by the time a patient comes to us, they have already done a lot of research, know that they’re in trouble, and don’t know what to do,” notes Dr. Bykerk. Nearly every day, physicians will contact Dr. Bykerk with questions such as “Have you ever seen this?” or “I’ve got this person who failed multiple medications. What would you do next?” “I’m more in the ‘induction and then back off model,’ rather than the current model of ‘go low, go slow,’” explains Dr. Bykerk. “I want to induce remission – of course, within the parameters of safety and tolerability for the patient. I prefer to think of my approach as intensive treatment, rather than aggressive treatment. My view is to treat early inflammatory arthritis more intensively at the beginning so that the disease doesn’t have a chance to become entrenched. I think RA is cancer-like in that the longer it’s established the less well a person will do or the more drug treatment they’re going to need over their lifetime. I work to try to find a way to get their disease under control as quickly as possible. Other doctors often ask me about my approach. It’s usually not what they’ve been taught.”

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Scleroderma and Vasculitis Robert F. Spiera, MD xxxxx

x

Determining an Accurate Diagnosis Case 1 A 35-year-old female was referred not for scleroderma but for Raynaud’s phenomenon and blood pressure issues. Based on certain findings in her fingernails on exam, as well as a blood test that came back positive, we diagnosed her not only with scleroderma, but with scleroderma renal crisis. With her presenting symptoms, she would have been otherwise diagnosed with undifferentiated connective tissue disease. Having seen so many cases of scleroderma, and especially by knowing how to examine nail folds, we were able to recognize features of this type of scleroderma early on and determine that her high blood pressure wasn’t the “garden variety” type, but rather a type that occurs with scleroderma that only responds to a specific therapy. If the patient had been continued on the standard blood pressure care, she could have lost kidney function. Since she was identified so early on, we were able to prevent her kidneys from failing. Case 2 A patient was referred by his treating physician for puffy hands and tingling in his fingers. The patient had undergone bilateral carpel tunnel releases, but it still didn’t explain why he had the swelling. It didn’t appear to the referring physician to be scleroderma because the patient did not present with Raynaud’s phenomenon or frank scleroderma changes of the skin. When I saw him, I suspected that he was in the early phase of a type of scleroderma associated with an antibody RNA polymerase III. Those patients can present with puffy hands and joint pain even before they have Raynaud’s. Typically, in most other forms of systemic scleroderma, the development of scleroderma is preceded by Raynaud’s. When the antibody for the condition was found to be positive, we managed the patient as if he had scleroderma. This, in turn, led to our being able to identify that he had the beginnings of scleroderma renal crisis. Case 3 A rheumatologist referred a patient with what he thought to be very bad Raynaud’s disease in the context of a scleroderma spectrum illness or possibly vasculitis. He called to ask for a recommendation beyond the basic management of the Raynaud’s because the patient had a very bad ulcer-like condition on his fingertips and it looked as though he might lose them. The presentation of his symptoms sounded somewhat strange for scleroderma. We were able to determine that while his condition mimicked scleroderma and Raynaud’s on some level, it was actually Buerger’s disease – a vascular problem related to smoking. The patient is now doing well following a surgical bypass procedure by one of the Hospital’s orthopaedic surgeons and by quitting smoking.

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As Director of the Scleroderma, Vasculitis, and Myositis Center of Excellence at Hospital for Special Surgery, Robert F. Spiera, MD, leads one of the few specialized scleroderma programs in the nation and has conducted a number of pioneering investigator-initiated trials of novel treatments for scleroderma and vasculitis. Dr. Spiera and his team completed Dr. Robert F. Spiera the first, longest, and largest prospective trial of imatinib mesylate in the treatment of scleroderma, observing an improvement in the skin thickening of most patients, as well as stability in pulmonary function tests. This class of medications (tyrosine kinase inhibitors) remains a candidate targeted therapy of interest in scleroderma. The Center’s Scleroderma Registry and Repository – a prospective, observational, longitudinal clinical database and biobank with more than 250 patients now enrolled – is providing biological specimens to facilitate basic scientific research studies to further elucidate the pathophysiology of scleroderma, develop biomarkers of disease activity, and understand predictors of outcome. A very active clinician, Dr. Spiera sees several hundred patients with scleroderma or vasculitis, and this volume of experience has made him the go-to rheumatologist for referring physicians. “Even if physicians are very comfortable with scleroderma, they want to be sure that they’re diagnosing the condition correctly and approaching it appropriately in terms of the evaluation and management plan,” notes Dr. Spiera. “With a very uncommon condition such as this, there’s often a comfort level knowing that you’re having it looked at by somebody who sees a lot of patients with this condition and its various types.” Dr. Spiera also plays a major role in clinical investigations – some of which are initiated and designed by him and his team, and some of which are trials of novel therapies offered by pharmaceutical companies. “In scleroderma, in particular, there have not been well-established, proven therapies,” says Dr. Spiera. “We’ve been involved in novel trials for drugs to address the disease itself, but also with drugs to address specific complications of the disease, such as fingertip ulcerations.” As an investigator on clinical trials that have led or may lead to more effective therapy for these disorders, Dr. Spiera often has patients referred to him by their physicians since he has access to and knowledge of newer, cutting edge clinical trials that might be relevant to their patients, as well as emerging therapies. “What I would like to emphasize,” says Dr. Spiera, “is that when patients are referred to me I’m not just providing an academic opinion; they’re seeing someone who’s very hands-on in patient care and who manages a lot of situations that are not frequently seen in general practice.” Hospital for Special Surgery

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contents 16

PROFESSIONAL STAFF

17 ENDOWED CHAIRS, PROFESSORSHIPS, AND FELLOWSHIPS

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SELECTED PUBLICATIONS

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CONTACT INFORMATION

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Professional Staff DEPARTMENT OF MEDICINE

Medical Staff

Physician-in-Chief, Director, Department of Medicine, and Chair, Rheumatology Division Mary K. Crow, MD, MACR

Attending Physicians Richard S. Bockman, MD, PhD Endocrinology Barry D. Brause, MD, FACP Chief, Infectious Disease Mary K. Crow, MD, MACR Physician-in-Chief Theodore R. Fields, MD, FACP Allan Gibofsky, MD, JD, DACP, FCLM Lionel B. Ivashkiv, MD Thomas J.A. Lehman, MD, FAAP Chief, Pediatric Rheumatology Michael D. Lockshin, MD, MACR C. Ronald MacKenzie, MD Steven K. Magid, MD Joseph A. Markenson, MD, FACP, MACR Stephen A. Paget, MD, FACP, MACR Jane E. Salmon, MD James P. Smith, MD Pulmonary Medicine Robert F. Spiera, MD

Perioperative Medicine Division Linda A. Russell, MD Director Rheumatology Faculty Practices Theodore R. Fields, MD, FACP Coordinator Bone Health and Osteoporosis Center of Excellence Linda A. Russell, MD Director Inflammatory Arthritis Center of Excellence Vivian P. Bykerk, MD Director Lupus and Antiphospholipid Syndrome Center of Excellence Jane E. Salmon, MD Director Scleroderma, Vasculitis, and Myositis Center of Excellence Robert F. Spiera, MD Director Rheumatology Fellowship Program Anne R. Bass, MD, FACP Director Jessica R. Berman, MD Associate Director Thomas J.A. Lehman, MD, FAAP Director, Pediatric Rheumatology Fellowship Program Alexa B. Adams, MD Associate Director, Pediatric Rheumatology Fellowship Program Academy of Rheumatology Medical Educators Stephen A. Paget, MD, FACP, MACR Director Jessica R. Berman, MD Associate Director Physicians-in-Chief Emeriti Charles L. Christian, MD, MACR Stephen A. Paget, MD, FACP, MACR Physicians Emeriti Lawrence J. Kagen, MD, MACR Irwin Nydick, MD Ernest Schwartz, MD

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Associate Attending Physicians Anne R. Bass, MD, FACP Jessica R. Berman, MD Vivian P. Bykerk, MD, FRCPC Lisa R. Callahan, MD Primary Care Sports Medicine Doruk Erkan, MD, MPH Susan M. Goodman, MD Brian C. Halpern, MD Chief, Primary Care Sports Medicine Lisa S. Ipp, MD Chief, Pediatrics Carol A. Mancuso, MD, FACP Jordan D. Metzl, MD Primary Care Sports Medicine Martin Nydick, MD Endocrinology, Perioperative Medicine Lisa R. Sammaritano, MD Sergio Schwartzman, MD Assistant Attending Physicians Alexa B. Adams, MD Pediatric Rheumatology Juliet B. Aizer, MD, MPH Ehimare I. Akhabue, MD Perioperative Medicine Panagiota Andreopoulou, MD Endocrinology Dalit Ashany, MD Laura V. Barinstein, MD Pediatric Rheumatology John W. Barnhill, MD Chief, Psychiatry Service

William W. Briner, Jr. MD Primary Care Sports Medicine Matthew L. Buchalter, MD Perioperative Medicine Trang M. Bui, MD, MPH Perioperative Medicine James J. Calloway III, MD Perioperative Medicine Hyun Susan Cha, MD Pediatrics Stephen J. Di Martino, MD, PhD Mary F. DiMaio MD Pediatrics Obinna D. Eneanya, MD Perioperative Medicine Marci A. Goolsby, MD Primary Care Sports Medicine Jessica K. Gordon, MD, MSc Michael W. Henry, MD Infectious Disease Wesley Hollomon, MD Perioperative Medicine James J. Kinderknecht, MD Primary Care Sports Medicine Osric S. King, MD Primary Care Sports Medicine Kyriakos A. Kirou, MD, DSc, FACP Mary J. Kollakuzhiyil, MD Perioperative Medicine Lawrence F. Levin, MD Chief, Cardiovascular Disease Alana B. Levine, MD Lisa A. Mandl, MD, MPH Charis Meng, MD Andrew O. Miller, MD Infectious Disease Marissa D. Newman, MD Perioperative Medicine Nancy Pan, MD Pediatric Rheumatology Edward J. Parrish, MD Stephanie L. Perlman, MD Pediatrics Nitin Roper, MD Perioperative Medicine Linda A. Russell, MD Director, Perioperative Medicine Jediah J. Sim, MD Perioperative Medicine Magdalena E. Swierczewski, MD Perioperative Medicine Lisa C. Vasanth, MD, MS Hendricks H. Whitman III, MD Arthur M.F. Yee, MD, PhD Christine M. Yu, MD Perioperative Medicine Florence Yu, MD Perioperative Medicine Hospital for Special Surgery

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Jennie Yu, MD Perioperative Medicine Instructor in Medicine George D. Kalliolias, MD, PhD Voluntary and Affiliated Medical Staff Attending Physicians Francis Perrone, MD Cardiovascular Disease Harry Spiera, MD Associate Attending Physicians Harry Bienenstock, MD Jessica G. Davis, MD Pediatrics, Genetics Gail E. Solomon, MD Pediatrics, Neurology Richard Stern, MD Assistant Attending Physicians Susan B. Bostwick, MD Pediatrics Michael S. Farber, MD Jacobo Futran, MD Flavia A. Golden, MD Michael I. Jacobs, MD Dermatology Bento R. Mascarenhas, MD Jacqueline M. Mayo, MD Lakshmi Nandini Moorthy, MD Pediatric Rheumatology Thomas M. Novella, DPM Podiatric Medicine Dana E. Orange, MD Sonal S. Parr, MD Alana C. Serota, MD Ariel D. Teitel, MD Mary Beth Walsh, MD Fellows in Rheumatology Soumya D. Chakravarty, MD, MS, PhD David Fernandez, MD Santhini Kasturi, MD Reena Khianey, MD Lindsay S. Lally, MD Konstantinos Loupasakis, MD, MS, PhD Sonali Narain, MBBS, MPH Danielle Ramsden-Stein, MD Elizabeth Schulman, MD Lauren Wong, MD Fellows in Pediatric Rheumatology Cassyanne Aguiar, MD Rose Karanicolas, MD, MT Farzana Nuruzzaman, MD Sarah Taber, MD Heather Walters, MD Division of Rheumatology

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Allied Health Professionals Nursing Linda Leff, RN, BSN, BC Director, Infusion Unit Monica Richey, MSN, ANP-BC/GNP Patricia Spergl, MSN, RN, ANP-BC Julie Pollino Tanner, RN, MA Nurse Manager Psychiatry Julia M. Kim, PhD Clinical Psychology Social Work Adena Batterman, MSW, LCSW Emily Dorfman, LMSW Suzan Fischbein, LMSW Roberta Horton, LCSW, ACSW Su Jin Kim, LCSW Juliette Kleinman, LCSW, ACSW Kathryn Klingenstein, LMSW Jillian Rose, LMSW Erica Sandoval, LMSW Mavis Seehaus, MS, LCSW Amy Silverman, LCSW My-Lan Tran, LCSW Research Staff

Named Chairs and professorships Endowed chairs, professorships, and fellowships recognize the generosity of our donors and sustain excellence in rheumatology care, research, and medical education. Franchellie M. Cadwell Chair Sergio Schwartzman, MD Collette Kean Research Chair Jane E. Salmon, MD David H. Koch Chair for Arthritis and Tissue Degeneration Research Lionel B. Ivashkiv, MD C. Ronald MacKenzie, MD, Chair in Ethics and Medicine C. Ronald MacKenzie, MD Richard L. Menschel Research Chair Steven R. Goldring, MD, MACR Stephen A. Paget, MD, Chair in Rheumatology Stephen A. Paget, MD, FACP, MACR Benjamin M. Rosen Chair in Immunology and Inflammation Research Mary K. Crow, MD, MACR

Leadership Steven R. Goldring, MD, MACR Chief Scientific Officer Lionel B. Ivashkiv, MD Associate Chief Scientific Officer and Director of Basic Research Robert N. Hotchkiss, MD Director of Clinical Research

Joseph P. Routh Professor of Rheumatic Diseases in Medicine Mary K. Crow, MD, MACR

Senior Scientists Franck J. Barrat, PhD Carl P. Blobel, MD, PhD Adele L. Boskey, PhD Mary K. Crow, MD, MACR Mary B. Goldring, PhD Lionel B. Ivashkiv, MD Alessandra B. Pernis, MD Jane E. Salmon, MD

St. Giles Research Chair supporting Theresa T. Lu, MD, PhD

Associate Scientists Theresa T. Lu, MD, PhD Stephen Lyman, PhD Inez Rogatsky, PhD Assistant Scientists Chitra Dahia, PhD Qiu Guo, PhD Xiaoyu Hu, MD, PhD Kyriakos A. Kirou, MD, DSc, FACP Kyung-Hun Park Min, PhD Xiaoping Qing, PhD Baohong Zhao, PhD

Virginia F. and William R. Salomon Chair in Musculoskeletal Research Carl P. Blobel, MD, PhD Peter J. Sharp Chair in Lupus Research Alessandra B. Pernis, MD

Starr Chair in Tissue Engineering Research supporting Chitra Dahia, PhD Russell F. Warren Research Chair supporting Suzanne A. Maher, PhD Named fellowships Charles L. Christian Research Fellowship Lisa Mandl, MD, MPH Ira W. DeCamp Fellowship in Musculoskeletal Genetics Mary B. Goldring, PhD Robert and Gillian Steel Fellowship in Musculoskeletal Research Inez Rogatsky, PhD Immunology and Inflammation Fellowship Sergei Rudchenko, PhD 17

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Selected Publications (November 2012 – November 2013)

Andreoli L, Chighizola CB, Banzato A, Pons-Estel GJ, de Jesus GR, Erkan D; on behalf of APS ACTION. The estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis. Arthritis Care & Research (Hoboken). 2013 Jul 16. [Epub ahead of print] Arnaud L, Mathian A, Ruffatti A, Erkan D, Tektonidou M, Cervera R, Forastiero R, Pengo V, Lambert M, Martinez-Zamora MA, Balasch J, Zuily S, Wahl D, Amoura Z. Efficacy of aspirin for the primary prevention of thrombosis in patients with antiphospholipid antibodies: an international and collaborative metaanalysis. Autoimmunity Reviews. 2013 Nov 2. [Epub ahead of print] Barbhaiya M, Erkan D. The optimal tool for assessment of organ damage in antiphospholipid syndrome. The Journal of Rheumatology. 2013 Jan;40(1):89. Barbhaiya M, Erkan D. Top 10 clinical research developments in antiphospholipid syndrome. Current Rheumatology Reports. 2013 Oct;15(10):367. Barnabe C, Xiong J, Pope JE, Boire G, Hitchon C, Haraoui B, Carter Thorne J, Tin D, Keystone EC, Bykerk VP; Canadian early ArThritis CoHort (CATCH) Study Investigators. Factors associated with time to diagnosis in early rheumatoid arthritis. Rheumatology International. 2013 Aug 30. [Epub ahead of print]. Barra L, Bykerk V, Pope JE, Haraoui BP, Hitchon CA, Thorne JC, Keystone EC, Boire G; The Catch Investigators. Anticitrullinated protein antibodies and rheumatoid factor fluctuate in early inflammatory arthritis and do not predict clinical outcomes. Journal of Rheumatology. 2013 Aug;40(8):1259-67.

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Berman H, Rodríguez-Pintó I, Cervera R, Morel N, Costedoat-Chalumeau N, Erkan D, Shoenfeld Y, Espinosa G; Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum on Antiphospholipid Antibodies). Rituximab use in the catastrophic antiphospholipid syndrome: descriptive analysis of the CAPS registry patients receiving rituximab. Autoimmunity Reviews. 2013 Sep;12(11):1085-90. Bernstein EJ, Mandl LA. Changing incidence of orthopedic surgery in rheumatic disease: contributing factors. Current Rheumatology Reports. 2013 Oct;15(10):365. Bernstein EJ, Mandl LA, Gordon JK, Spiera RF, Horn EM. The submaximal heart and pulmonary evaluation: a novel noninvasive test to identify pulmonary hypertension in patients with systemic sclerosis. Arthritis Care and Research. 2013 Oct;65(10):1713-18. Biswas PS, Kang K, Gupta S, Bhagat G, Pernis AB. A murine autoimmune model of rheumatoid arthritis and systemic lupus erythematosus associated with deregulated production of IL-17 and IL-21. Methods in Molecular Biology. 2012;900:233-51. Boyd TA, Bonner A, Thorne C, Boire G, Hitchon C, Haraoui BP, Keystone EC, Bykerk VP, Pope JE. The Relationship Between Function and Disease Activity as Measured by the HAQ and DAS28 Varies Over Time and by Rheumatoid Factor Status in Early Inflammatory Arthritis (EIA). Results from the CATCH Cohort. The Open Rheumatology Journal. 2013 Aug 28;7:58-63. Burton L, Paget D, Binder NB, Bohnert K, Nestor BJ, Sculco TP, Santambrogio L, Ross FP, Goldring SR, Purdue PE. Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation. Journal of Orthopaedic Research. 2013 Jan;31(1):73-80.

Buttgereit F, Gibofsky A. Delayedrelease prednisone – a new approach to an old therapy. Expert Opinion on Pharmacotherapy. 2013 Jun;14(8):1097-106. Bykerk VP, Cush J, Winthrop K, Calabrese L, Lortholary O, de Longueville M, van Vollenhoven R, Mariette X. Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials. Annals of the Rheumatic Diseasess. 2013 Oct 3. [Epub ahead of print] Bykerk VP, Keystone EC, Kuriya B, Larché M, Thorne JC, Haraoui B. Achieving remission in clinical practice: lessons from clinical trial data. Clinical and Experimental Rheumatology. 2013 Jul-Aug;31(4):621-32. Bykerk VP, Massarotti EM. The new ACR/ EULAR remission criteria: rationale for developing new criteria for remission. Rheumatology. 2012 Dec;51 Suppl 6:vi16-20. Bykerk VP, Schoels MM. Treatment strategies for early rheumatoid arthritis. Current Opinion in Rheumatology. 2013 May;25(3):375-83. Caglič D, Repnik U, Jedeszko C, Kosec G, Miniejew C, Kindermann M, Vasiljeva O, Turk V, Wendt KU, Sloane BF, Goldring MB, Turk B. The proinflammatory cytokines interleukin-1α and tumor necrosis factor α promote the expression and secretion of proteolytically active cathepsin S from human chondrocytes. The Journal of Biological Chemistry. 2013 Feb;394(2):307-16. Chakravarty SD, Markenson JA. Rheumatic manifestations of endocrine disease. Current Opinion in Rheumatology. 2013 Jan;25(1):37-43. Chakravarty SD, Poulikakos PI, Ivashkiv LB, Salmon JE, Kalliolias GD. Kinase inhibitors: a new tool for the treatment of rheumatoid arthritis. Clinical Immunology. 2013 Jul;148(1):66-78. Chinenov Y, Gupte R, Rogatsky I. Nuclear receptors in inflammation control: repression by GR and beyond. Molecular and Cellular Endocrinology. 2013 Nov5; 380(1-2):55-64.

Hospital for Special Surgery

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Choy T, Bykerk VP, Boire G, Haraoui BP, Hitchon C, Thorne C, Keystone EC, Pope JE; on behalf of CATCH Investigators. Physician global assessment at 3 months is strongly predictive of remission at 12 months in early rheumatoid arthritis: results from the CATCH cohort. Rheumatology (Oxford). 2013 Nov 15. [Epub ahead of print] Chung L, Domsic RT, Lingala B, Alkassab F, Bolster M, Csuka ME, Derk C, Fischer A, Frech T, Furst DE, Gomberg-Maitland M, Hinchcliff M, Hsu V, Hummers LK, Khanna D, Medsger TA Jr, Molitor JA, Preston IR, Schiopu E, Shapiro L, Silver R, Simms R, Varga J, Gordon JK, Steen VD. Survival and predictors of mortality in systemic sclerosis associated pulmonary arterial hypertension: outcomes from the PHAROS registry. Arthritis Care & Research (Hoboken). 2013 Aug 27. [Epub ahead of print] de Andrés MC, Imagawa K, Hashimoto K, Gonzalez A, Roach HI, Goldring MB, Oreffo RO. Loss of methylation in CpG sites in the NF-κB enhancer elements of inducible nitric oxide synthase is responsible for gene induction in human articular chondrocytes Arthritis & Rheumatism. 2013 Mar;65(3):732-42. Diana J, Simoni Y, Furio L, Beaudoin L, Agerberth B, Barrat F, Lehuen A. Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes. Nature Medicine. 2013 Jan;19(1):65-73. Erkan D, Pierangeli SS. Could statins be a new therapeutic option for antiphospholipid syndrome patients? Expert Review of Hematology. 2013 Apr;6(2):115-17. Erkan D, Vega J, Ramón G, Kozora E, Lockshin MD. A pilot open-label phase II trial of rituximab for non-criteria manifestations of antiphospholipid syndrome. Arthritis & Rheumatism. 2013 Feb;65(2):464-71.

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Erkan D, Willis R, Murthy VL, Basra G, Vega J, Ruiz-Limón P, Carrera AL, Papalardo E, Martínez-Martínez LA, González EB, Pierangeli SS. A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients. Annals of the Rheumatic Diseasess. 2013 Aug 9. [Epub ahead of print] Espinosa G, Rodríguez-Pintó I, GomezPuerta JA, Pons-Estel G, Cervera R; Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum on Antiphospholipid Antibodies). Relapsing catastrophic antiphospholipid syndrome potential role of microangiopathic hemolytic anemia in disease relapses. Seminars in Arthritis & Rheumatism. 2013 Feb;42(4):417-23. Forbess LJ, Gordon JK, Doobay K, Bosworth BP, Lyman S, Davids ML, Spiera RF. Low prevalence of coeliac disease in patients with systemic sclerosis: a cross-sectional study of a registry cohort. Rheumatology. 2013 May;52(5):939-43. Frech TM, Shanmugam VK, Shah AA, Assassi S, Gordon JK, Hant FN, Hinchcliff ME, Steen V, Khanna D, Kayser C, Domsic RT. Treatment of early diffuse systemic sclerosis skin disease. Clinical and Experimental Rheumatology. 2013 Mar-Apr;31(2 Suppl 76):166-71. Freedman BI, Langefeld CD, Andringa KK, Croker JA, Williams AH, Garner NE, Birmingham DJ, Hebert LA, Hicks PJ, Segal MS, Edberg JC, Brown EE, Alarcon GS, Costenbader KH, Comeau ME, Criswell LA, Harley JB, James JA, Kamen DL, Lim SS, Merrill JT, Sivils KL, Niewold TB, Patel NM, Petri M, RamseyGoldman R, Reveille JD, Salmon JE, Tsao BP, Gibson KL, Byers JR, Vinnikova AK, Lea JP, Julian BA, Kimberly RP; on behalf of the Lupus Nephritis-ESKD Consortium. End-stage kidney disease in African Americans with lupus nephritis associates with APOL1. Arthritis & Rheumatism. 2013 Oct 21. [Epub ahead of print]

Fröhlich C, Klitgaard M, Noer JB, Kotzsch A, Nehammer C, Kronqvist P, Berthelsen J, Blobel C, Kveiborg M, Albrechtsen R, Wewer UM. ADAM12 is expressed in the tumour vasculature and mediates ectodomain shedding of several membrane-anchored endothelial proteins. Biochemical Journal. 2013 May 15;452(1):97-109. Furst DE, Keystone EC, So AK, Braun J, Breedveld FC, Burmester GR, De Benedetti F, Dörner T, Emery P, Fleischmann R, Gibofsky A, Kalden JR, Kavanaugh A, Kirkham B, Mease P, Rubbert-Roth A, Sieper J, Singer NG, Smolen JS, Van Riel PL, Weisman MH, Winthrop KL. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012. Annals of the Rheumatic Diseases. 2013 Apr;72 Suppl 2:ii2-34. Ghomrawi HM, Mancuso CA, Westrich GH, Marx RG, Mushlin AI; Expectations Discordance Study Group. Discordance in TKA expectations between patients and surgeons. Clinical Orthopaedics and Related Research. 2013 Jan;471(1):175-80. Gibofsky A. Comparative effectiveness of current treatments for rheumatoid arthritis. American Journal of Managed Care. 2012 Dec;18(13 Suppl):S303-14. Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. American Journal of Managed Care. 2012 Dec;18(13 Suppl):S295-302. Gibofsky A, Silberstein S, Argoff C, Daniels S, Jensen S, Young CL. Lower-dose diclofenac submicron particle capsules provide early and sustained acute patient pain in a phase 3 study. Postgraduate Medicine. 2013 Sep;125(5):130-38. Goldring SR. Osteoimmunology and bone homeostasis: relevance to spondyloarthritis. Current Rheumatology Reports. 2013 Jul;15(7):342. Goldring SR, Purdue PE, Crotti TN, Shen Z, Flannery MR, Binder NB, Ross FP, McHugh KP. Bone remodelling in inflammatory arthritis. Annals of the Rheumatic Diseases. 2013 Apr;72 Suppl 2:ii52-55. 19

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Selected Publications Goldring MB. Insight into the function of DIO2, a susceptibility gene in human osteoarthritis, as an inducer of cartilage damage in a rat model: is there a role for chondrocyte hypertrophy? Osteoarthritis Cartilage. 2013 May;21(5):643-45. Goodman SM. Rheumatoid arthritis: preoperative evaluation for total hip and total knee replacement surgery. Journal of Clinical Rheumatology. 2013 Jun;19(4): 187-92. Goodman SM, Figgie M. Lower extremity arthroplasty in patients with inflammatory arthritis: preoperative and perioperative management. Journal of the American Academy of Orthopaedic Surgeons. 2013 Jun;21(6):355-63. Goodman SM, Mackenzie CR. Cardiovascular risk in the rheumatic disease patient undergoing orthopedic surgery. Current Rheumatology Reports. 2013 Sep;15(9):354. Goodman SM, Paget S. Perioperative drug safety in patients with rheumatoid arthritis. Rheumatic Disease Clinics of North America. 2012 Nov;38(4):747-59. Groot AJ, Cobzaru C, Weber S, Saftig P, Blobel CP, Kopan R, Vooijs M, Franzke CW. Epidermal ADAM17 is dispensable for notch activation. Journal of Investigative Dermatology. 2013 Sep;133(9):2286-8. Guaiquil VH, Hewing NJ, Chiang MF, Rosenblatt MI, Chan RV, Blobel CP. A murine model for retinopathy of prematurity identifies endothelial cell proliferation as a potential mechanism for plus disease. Investigative Ophthalmology & Visual Science. 2013 Aug 7;54(8): 5294-302. Gulati CM, Satlin MJ, Magro CM, Kirou KA. Two systemic lupus erythematosus patients with severe pleurisy: similar presentations, different causes. Arthritis Care & Research. 2013 Jun;65(6):1005-13. Gupte R, Muse GW, Chinenov Y, Adelman K, Rogatsky I. Glucocorticoid receptor represses proinflammatory genes at distinct steps of the transcription cycle. Proceedings of the National Academy of Sciences (USA). 2013 Sep 3;110(36): 14616-21. 20

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Hall KC, Hill D, Otero M, Plumb DA, Froemel D, Dragomir CL, Maretzky T, Boskey A, Crawford HC, Selleri L, Goldring MB, Blobel CP. ADAM17 controls endochondral ossification by regulating terminal differentiation of chondrocytes. Molecular and Cellular Biology. 2013 Aug;33(16):3077-90. Harris JA, Bykerk VP, Hitchon CA, Keystone EC, Thorne JC, Boire G, Haraoui B, Hazlewood G, Bonner AJ, Pope JE; CATCH Investigators. Determining best practices in early rheumatoid arthritis by comparing differences in treatment at sites in the Canadian Early Arthritis Cohort. The Journal of Rheumatology. 2013 Nov;40(11):1823-30. Hashimoto K, Otero M, Imagawa K, de Andrés MC, Coico JM, Roach HI, Oreffo RO, Marcu KB, Goldring MB. Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites. The Journal of Biological Chemistry. 2013 Apr 5;288(14):10061-72. Hazlewood GS, Naimark D, Gardam M, Bykerk VP, Bombardier C. Prophylaxis for latent tuberculosis infection prior to antiTNF therapy in low-risk elderly patients with rheumatoid arthritis: a decision analysis. Arthritis Care & Research. 2013 Jul 8. [Epub ahead of print] Hewing NJ, Weskamp G, Vermaat J, Farage E, Glomski K, Swendeman S, Chan RV, Chiang MF, Khokha R, AnandApte B, Blobel CP. Intravitreal injection of TIMP3 or the EGFR inhibitor erlotinib offers protection from oxygen-induced retinopathy in mice. Investigative Ophthalmology & Visual Science. 2013 Jan 30;54(1):864-70. Houard X, Goldring MB, Berenbaum F. Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Current Rheumatology Reports. 2013 Nov;15(11):375.

Isgro J, Gupta S, Jacek E, Pavri T, Duculan R, Kim M, Kirou KA, Salmon JE, Pernis AB. Enhanced rho-associated protein kinase activation in patients with systemic lupus erythematosus. Arthritis & Rheumatism. 2013 Jun;65(6):1592-602. Issuree PD, Maretzky T, McIlwain DR, Monette S, Qing X, Lang PA, Swendeman SL, Park-Min KH, Binder N, Kalliolias GD, Yarilina A, Horiuchi K, Ivashkiv LB, Mak TW, Salmon JE, Blobel CP. iRHOM2 is a critical pathogenic mediator of inflammatory arthritis. Journal of Clinical Investigation. 2013 Feb 1;123(2):928-32. Ivashkiv LB. Epigenetic regulation of macrophage polarization and function. Trends in Immunology. 2013 May;34(5):216-23. Ivashkiv LB. PTPN22 in autoimmunity: different cell and different way. Immunity. 2013 Jul 25;39(1):91-93. Jacek E, Fallon BA, Chandra A, Crow MK, Wormser GP, Alaedini A. Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits. Journal of Neuroimmunology. 2013 Feb 15;255(12):85-91. Jacobs JJ, King TR, Klippel JH, Berven SH, Burr DB, Caskey PM, Elderkin AL, Esposito PW, Gall EP, Goldring SR, Pollak AN, Sandborg CI, Templeton KJ. Beyond the decade: strategic priorities to reduce the burden of musculoskeletal disease. The Journal of Bone & Joint Surgery (Am). 2013 Sep 4;95(17):e1251-6. Johnson BK, Goodman SM, Alexiades MM, Figgie MP, Demmer RT, Mandl LA. Patterns and associated risk of perioperative use of anti-tumor necrosis factor in patients with rheumatoid arthritis undergoing total knee replacement. Journal of Rheumatology. 2013 May;40(5):617-23. Kader M, Smith AP, Guiducci C, Wonderlich ER, Normolle D, Watkins SC, Barrat FJ, Barratt-Boyes SM. Blocking TLR7- and TLR9-mediated IFN-α production by plasmacytoid dendritic cells does not diminish immune activation in early SIV infection. PLoS Pathogens. 2013 Jul;9(7):e1003530. Hospital for Special Surgery

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Kavanaugh A, Fleischmann R, Bergman MJ, Ruderman E, Troum O, Wells AF, Martin G, Calabrese LH, Gibofsky A, Strand V, Cush JJ. Proceedings of the 2013 Rheumatology Winter Clinical Symposia. Seminars in Arthritis and Rheumatism. 2013 Jun;42(6):667-73. Katz JN, Brophy RH, Chaisson CE, de Chaves L, Cole BJ, Dahm DL, Donnell-Fink LA, Guermazi A, Haas AK, Jones MH, Levy BA, Mandl LA, Martin SD, Marx RG, Miniaci A, Matava MJ, Palmisano J, Reinke EK, Richardson BE, Rome BN, Safran-Norton CE, Skoniecki DJ, Solomon DH, Smith MV, Spindler KP, Stuart MJ, Wright J, Wright RW, Losina E. Surgery versus physical therapy for a meniscal tear and osteoarthritis. The New England Journal of Medicine. 2013 May 2;368(18):1675-84. Kirou KA, Gkrouzman E. Anti-interferon alpha treatment in SLE. Clinical Immunology. 2013 Sep;148(3):303-12. Ko FC, Dragomir C, Plumb DA, Goldring SR, Wright TM, Goldring MB, van der Meulen MC. In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae. Arthritis & Rheumatism. 2013 Jun;65(6):1569-78. Kozora E, Erkan D, West SG, Filley CM, Zhang L, Ramon G, Duggan E, Lockshin MD. Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE). Lupus. 2013 Jan;22(1):73-80. Kozora E, Erkan D, Zhang L, Zimmerman R, Ramon G, Ulug AM, Lockshin MD. Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) versus aPL-positive non-SLE patients. Clinical and Experimental Rheumatology. 2013 Sep 10. [Epub ahead of print] Lally L, Spiera RF. Biomarkers in ANCAassociated vasculitis. Current Rheumatology Reports. 2013 Oct;15(10):363. Lee A, Qiao Y, Grigoriev G, Chen J, ParkMin KH, Park SH, Ivashkiv LB, Kalliolias GD. Tumor necrosis factor Îą induces sustained signaling and a prolonged and unremitting inflammatory response in Division of Rheumatology

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rheumatoid arthritis synovial fibroblasts. Arthritis & Rheumatism. 2013 Apr;65(4): 928-38. Lee YC, Lu B, Boire G, Haraoui BP, Hitchon CA, Pope JE, Thorne JC, Keystone EC, Solomon DH, Bykerk VP. Incidence and predictors of secondary fibromyalgia in an early arthritis cohort. Annals of the Rheumatic Diseasess. 2013 Jun;72(6):949-54. Lehman TJ. Paediatric rheumatology: where are the innovations in paediatric rheumatology? Nature Reviews Rheumatology. 2013 Jun;9(6):326-27. Lie E, Woodworth TG, Christensen R, Kvien TK, Bykerk V, Furst DE, Bingham CO 3rd, Choy EH; the OMERACT RA Flare Working Group. Validation of OMERACT preliminary rheumatoid arthritis flare domains in the NOR-DMARD study. Annals of the Rheumatic Diseasess. 2013 Jul 12. [Epub ahead of print] Lockshin MD. Editorial: splitting headache (off). Arthritis & Rheumatism. 2013 Nov;65(11):2759-61. Lockshin MD. Anticoagulation in management of antiphospholipid antibody syndrome in pregnancy. Clinics in Laboratory Medicine. 2013 Jun;33(2): 367-76. Lockshin MD. Pregnancy and antiphospholipid syndrome. American Journal of Reproductive Medicine. 2013 Jun;69(6):585-87. Lockshin MD, Cohn E, Aslam A, Buyon JP, Salmon JE. Sex ratios among children of lupus pregnancies. Arthritis & Rheumatism. 2013 Jan;65(1):282. Lockshin MD, Cohn E, Aslam A, Buyon JP, Salmon JE. Reply. Arthritis & Rheumatism. 2013 Apr;65(4):1129-30. Maass PG, Rump A, Schulz H, Stricker S, Schulze L, Platzer K, Aydin A, Tinschert S, Goldring MB, Luft FC, Bähring S. A misplaced lncRNA causes brachydactyly in humans. The Journal of Clinical Investigation. 2012 Nov 1;122(11): 3990-4002. MacKenzie CR, Matava MJ, Carroll C 4th. Surgery for placebo effect? Virtual Mentor. 2012 Nov 1;14(11):825-34.

MacKenzie CR, Meltzer M, Kitsis EA, Mancuso CA. Ethical challenges in rheumatology: a survey of the American College of Rheumatology Membership. Arthritis & Rheumatism. 2013 Oct;65(10):2524-32. Mancuso CA, Cammisa FP, Sama AA, Hughes AP, Ghomrawi HM, Girardi FP. Development and testing of an expectations survey for patients undergoing lumbar spine surgery. The Journal of Bone & Joint Surgery (Am). 2013 Oct 2;95(19):1793-800. Mancuso CA, Cammisa FP, Sama AA, Hughes AP, Girardi FP. Development of an expectations survey for patients undergoing cervical spine surgery. Spine. 2012 Nov 7. [Epub ahead of print] Mancuso CA, Choi TN, Westermann H, Wenderoth S, Wells MT, Charlson ME. Improvement in asthma quality of life in patients enrolled in a prospective study to increase lifestyle physical activity. Journal of Asthma. 2013 Feb;50(1):103-07. Mandl LA. Determining who should be referred for total hip and knee replacements. Nature Reviews Rheumatology. 2013 Jun;9(6):351-57. Mandl LA, Lyman S, Quinlan P, Bailey T, Katz J, Magid SK. Falls among patients who had elective orthopaedic surgery: a decade of experience from a musculoskeletal specialty hospital. Journal of Orthopaedic & Sports Physical Therapy. 2013 Feb;43(2):91-96. Maretzky T, McIlwain DR, Issuree PD, Li X, Malapeira J, Amin S, Lang PA, Mak TW, Blobel CP. iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding. Proceedings of the National Academy of Sciences USA. 2013 Jul 9;110(28):11433-38. Markenson JA, Koenig AS, Feng JY, Chaudhari S, Zack DJ, Collier D, Weaver A. Comparison of physician and patient global assessments over time in patients with rheumatoid arthritis: a retrospective analysis from the RADIUS cohort. Journal of Clinical Rheumatology. 2013 Sep;19(6):317-23.

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Selected Publications Mavragani CP, Niewold TB, Chatzigeorgiou A, Danielides S, Thomas D, Kirou KA, Kamper E, Kaltsas G, Crow MK. Increased serum type I interferon activity in organspecific autoimmune disorders: clinical, imaging, and serological associations. Frontiers in Immunology. 2013 Aug 19;4:238. Memtsoudis SG, Hargett M, Russell LA, Parvizi J, Cats-Baril WL, Stundner O, Sculco TP; Consensus Conference on Bilateral Total Knee Arthroplasty Group. Consensus statement from the consensus conference on bilateral total knee arthroplasty group. Clinical Orthopaedics and Related Research. 2013 Aug;471(8):2649-57. Miloslavsky E, Specks U, Merkel P, Seo P, Spiera R, Langford C, Hoffman G, Kallenberg C, St Clair E, Tchao N, Viviano L, Ding L, Sejismundo L, Mieras K, Ikle D, Jepson B, Mueller M, Brunetta P, Allen N, Fervenza F, Geetha D, Keogh K, Kissin E, Monach P, Peikert T, Stegeman C, Ytterberg S, Stone H; for the RAVE-ITN Research Group. Clinical outcomes of remission induction therapy for severe ANCA-Associated vasculitis. Arthritis & Rheumatism. 2013 Sep;65(9):2441-49. Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Iklé D, Kallenberg CG, Krischer J, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Johnson KJ, Merkel PA. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Annals of the Rheumatic Diseasess. 2013 Aug;72(8):1342-50. Moorthy LN, Saad-Magalhães C, Sato JO, Len CA, Vasco MB, Appenzeller S, Marini R, Oliveira SK, Rodrigues M, Sztajnbok F, Almeida RG, Jesus AA, Campos LM, Silva CA, Peterson MG, Hassett AL, Weiss E, Verma S, Dahodwala MQ, Lehman TJ. Validation of the Portuguese Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) in Brazil. Lupus. 2013;22(2):190-97.

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Moorthy LN, Weiss E, Peterson MG, Hassett AL, Lehman TJ; International SMILEY Collaborative Group. An update on cross-cultural adaptation of U.S. English SMILEY. Lupus. 2012 Nov;21(13):1450-54. Mulla MJ, Salmon JE, Chamley LW, Brosens JJ, Boeras CM, Kavathas PB, Abrahams VM. A role for uric acid and the Nalp3 inflammasome in antiphospholipid antibody-induced IL-1ß production by human first trimester trophoblast. PLoS One. 2013 Jun 6;8(6):e65237. Mussen L, Boyd T, Bykerk VP, de Leon F, Li L, Boire G, Hitchon C, Haraoui B, Thorne JC, Pope J. Low prevalence of work disability in early inflammatory arthritis (EIA) and early rheumatoid arthritis at enrollment into a multi-site registry: results from the CATCH cohort. Rheumatology International. 2013 Feb;33(2):457-65. O’Dell JR, Mikuls TR, Taylor TH, Ahluwalia V, Brophy M, Warren SR, Lew RA, Cannella AC, Kunkel G, Phibbs CS, Anis AH, Leatherman S, Keystone E; CSP 551 RACAT Investigators. Therapies for active rheumatoid arthritis after methotrexate failure. The New England Journal of Medicine. 2013 Jul 25;369(4):307-18. Olivotto E, Otero M, Astolfi A, Platano D, Facchini A, Pagani S, Flamigni F, Facchini A, Goldring MB, Borzì RM, Marcu KB. IKKα/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation. PLoS One. 2013 Sep 2;8(9):e73024. Orange DE, Blachere NE, Fak J, Parveen S, Frank MO, Herre M, Tian S, Monette S, Darnell RB. Dendritic cells loaded with FK506 kill T cells in an antigen-specific manner and prevent autoimmunity in vivo. eLife. 2013;2:e00105. Ortel TL, Kitchens CS, Erkan D, Brandão LR, Hahn S, James AH, Kulkarni R, Manco-Johnson MJ, Pericak-Vance M, Vance J. Clinical causes and treatment of the thrombotic storm. Expert Review of Hematology. 2012 Dec;5(6):653-59.

Paget SA. The role of imaging studies in today’s rheumatology. Rheumatic Disease Clinics of North America. 2013 Aug;39(3):xi-xiv. Paget SA. The microbiome, autoimmunity, and arthritis: cause and effect: an historical perspective. Transactions of the American Clinical and Climatological Association. 2012;123:257-66. Pan N, Herzog R, Blanco JS, Nauseef WM, Jenkins S, Kovanlikaya A, Salvatore CM, Toussi SS. Candida albicans osteomyelitis in an infant: a case report and literature review. Journal of Pediatric Orthopaedics B. 2013 Sep;22(5):491-97. Park-Min KH, Lee EY, Moskowitz NK, Lim E, Lee SK, Lorenzo JA, Huang C, Melnick AM, Purdue PE, Goldring SR, Ivashkiv LB. Negative regulation of osteoclast precursor differentiation by CD11b and ß2 integrin-B-cell lymphoma 6 signaling. Journal of Bone and Mineral Research. 2013 Jan;28(1):135-49. Peterson JC, Czajkowski S, Charlson ME, Link AR, Wells MT, Isen AM, Mancuso CA, Allegrante JP, Boutin-Foster C, Ogedegbe G, Jobe JB. Translating basic behavioral and social science research to clinical application: the EVOLVE mixed methods approach. Journal of Consulting and Clinical Psychology. 2013 Apr;81(2):217-30. Pyne L, Bykerk VP, Boire G, Haraoui B, Hitchon C, Thorne JC, Keystone EC, Pope JE; CATCH Investigators. Increasing treatment in early rheumatoid arthritis is not determined by the disease activity score but by physician global assessment: results from the CATCH study. Journal of Rheumatology. 2012 Nov;39(11):2081-87. Qiao Y, Giannopoulou EG, Chan CH, Park SH, Gong S, Chen J, Hu X, Elemento O, Ivashkiv LB. Synergistic activation of inflammatory cytokine genes by interferon-γ-induced chromatin remodeling and toll-like receptor signaling. Immunity. 2013 Sep 19;39(3):454-69.

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Ricciardi BF, Paul J, Kim A, Russell LA, Lane JM. Osteoporosis drug therapy strategies in the setting of diseasemodifying agents for autoimmune disease. Osteoporosis International. 2013 Feb;24(2):423-32. Ritter SY, Subbaiah R, Bebek G, Crish J, Scanzello CR, Krastins B, Sarracino D, Lopez MF, Crow MK, Aigner T, Goldring MB, Goldring SR, Lee DM, Gobezie R, Aliprantis AO. Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis & Rheumatism. 2013 Apr;65(4):981-92. Rogatsky I, Chandrasekaran U, Manni M, Yi W, Pernis AB. Epigenetics and the IRFs: a complex interplay in the control of immunity and autoimmunity. Autoimmunity. 2013 Nov 11. [Epub ahead of print] Russell LA. Osteoporosis and orthopedic surgery: effect of bone health on total joint arthroplasty outcome. Current Rheumatology Reports. 2013 Nov;15(11):371. Sammaritano LR. Pregnancy in rheumatic disease patients. Journal of Clinical Rheumatology. 2013 Aug;19(5):259-66. Schwartzman S, Schwartzman M. Whipple’s disease. Rheumatic Disease Clinics of North America. 2013 May;39(2):313-21. Scanzello CR, Albert AS, DiCarlo E, Rajan KB, Kanda V, Asomugha EU, Swaim BH, Katz JN, Goldring SR, Richmond JC, McKeon B. The influence of synovial inflammation and hyperplasia on symptomatic outcomes up to 2 years postoperatively in patients undergoing partial meniscectomy. Osteoarthritis Cartilage. 2013 Sep;21(9):1392-99. Schoels MM, van der Heijde D, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, et al. Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and metaanalysis informing a consensus statement. Annals of the Rheumatic Diseases. 2013 Apr;72(4):583-89.

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Smolen JS, Schoels MM, Nishimoto N, Breedveld FC, Burmester GR, Dougados M, Emery P, Ferraccioli G, Gabay C, Gibofsky A, Gomez-Reino JJ, Jones G, Kvien TK, Murakami M, Betteridge N, Bingham CO 3rd, Bykerk V, Choy EH, Combe B, Cutolo M, Graninger W, Lanas A, MartinMola E, Montecucco C, Ostergaard M, Pavelka K, Rubbert-Roth A, Sattar N, Scholte-Voshaar M, Tanaka Y, Trauner M, Valentini G, Winthrop KL, de Wit M, van der Heijde D. Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions. Annals of the Rheumatic Diseases. 2013 Apr;72(4):482-92. Smolen JS, van der Heijde DM, Keystone EC, van Vollenhoven RF, Goldring MB, Guérette B, Cifaldi MA, Chen N, Liu S, Landewé RB. Association of joint space narrowing with impairment of physical function and work ability in patients with early rheumatoid arthritis: protection beyond disease control by adalimumab plus methotrexate. Annals of the Rheumatic Diseases. 2013 Jul;72(7):1156-62. Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP, Mieras K, Stone JH; RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. The New England Journal of Medicine. 2013 Aug 1;369(5):417-27. Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Park-Min KH, Lee EY, Moskowitz NK, Lim E, Lee SK, Lorenzo JA, Huang C, Melnick AM, Purdue PE, Goldring SR, Ivashkiv LB. Negative regulation of osteoclast precursor differentiation by CD11b and ß2 integrin-Bcell lymphoma 6 signaling. Journal of Bone and Mineral Research. 2013 Jan;28(1):135-49.

Steensma MR, Tyler WK, Shaber AG, Goldring SR, Ross FP, Williams BO, Healey JH, Purdue PE. Targeting the giant cell tumor stromal cell: functional characterization and a novel therapeutic strategy. PLoS One. 2013 Jul 26;8(7):e69101. Steiman AJ, Pope JE, Thiessen-Philbrook H, Li L, Barnabe C, Kalache F, Kung T, Bessette L, Flanagan C, Haraoui B, Hochman J, Leclercq S, Mosher D, Thorne C, Bykerk V. Non-biologic disease-modifying antirheumatic drugs (DMARDs) improve pain in inflammatory arthritis (IA): a systematic literature review of randomized controlled trials. Rheumatology International. 2013 May;33(5):1105-20. Strober BE, Clay Cather J, Cohen D, Crowley JJ, Gordon KB, Gottlieb AB, Kavanaugh AF, Korman NJ, Krueger GG, Leonardi CL, Schwartzman S, Sobell JM, Solomon GE, Young M. A Delphi consensus approach to challenging case scenarios in moderate-to-severe psoriasis: Part 1. Dermatology and Therapy. 2012 Dec;2(1):1. Strober BE, Clay Cather J, Cohen D, Crowley JJ, Gordon KB, Gottlieb AB, Kavanaugh AF, Korman NJ, Krueger GG, Leonardi CL, Schwartzman S, Sobell JM, Solomon GE, Young M. A Delphi consensus approach to challenging case scenarios in moderate-to-severe psoriasis: Part 2. Dermatology and Therapy. 2012 Dec;2(1):2. Stundner O, Chiu YL, Sun X, Goodman SM, Russell LA, Calloway JJ, Mackenzie CR, Mazumdar M, Memtsoudis SG. Perioperative outcomes in patients with rheumatoid versus osteoarthritis for total hip arthroplasty: a populationbased study. Clinical and Experimental Rheumatology. 2013 Nov 14. [Epub ahead of print]

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Selected Publications Stundner O, Danninger T, Chiu YL, Sun X, Goodman SM, Russell LA, Figgie M, Mazumdar M, Memtsoudis SG. Rheumatoid arthritis vs osteoarthritis in patients receiving total knee arthroplasty: perioperative outcomes. The Journal of Arthroplasty. 2013 Jun 11. [Epub ahead of print] Tavares R, Huang S, Bykerk VP, Bell MJ. A parallel group cohort to determine the measurement properties of an early inflammatory arthritis detection tool. Rheumatology (Oxford). 2013 Nov;52(11):2077-85. Tavares R, Pope JE, Tremblay JL, Thorne C, Bykerk VP, Lazovskis J, Blocka KL, Bell MJ, Lacaille D, Hitchon CA, Fitzgerald AA, Fidler WK, Bookman AA, Henderson JM, Mosher DP, Sholter DE, Khraishi M, Haraoui B, Chen H, Li X, Laupacis A, Boire G, Tomlinson G, Bombardier C. Time to disease-modifying antirheumatic drug treatment in rheumatoid arthritis and its predictors: a national, multicenter, retrospective cohort. Journal of Rheumatology. 2012 Nov;39(11):2088-97. Tavares R, Wells GA, Bykerk VP, Guillemin F, Tugwell P, Bell MJ. Validation of a self-administered inflammatory arthritis detection tool for rheumatology triage. Journal of Rheumatology. 2013 Apr;40(4):417-24. Toussi SS, Pan N, Walters HM, Walsh TJ. Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis alpha inhibitors: a systematic review of the literature. Clinical Infectious Diseases. 2013 Aug 26. [Epub ahead of print] Trencheva K, Morrissey KP, Wells M, Mancuso CA, Lee SW, Sonoda T, Michelassi F, Charlson ME, Milsom JW. Reply to Letter: “Identifying Important Predictors for Anastomotic Leak After Colon and Rectal Resection: Prospective Study on 616 Patients.” Annals of Surgery. 2013 Oct 4. [Epub ahead of print] Uludag O, Erkan D, Lockshin MD. Cognitive or cosmetic dysfunction? Arthritis & Rheumatism. 2012 Dec;64 (12):4134.

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Unizony SH, Dasgupta B, Fisheleva E, Rowell L, Schett G, Spiera R, Zwerina J, Harari O, Stone JH. International Journal of Rheumatology. 2013; 912562. Unnanuntana A, Saleh A, Nguyen JT, Sculco TP, Cornell CN, Mancuso CA, Lane JM. Low vitamin D status does not adversely affect short-term functional outcome after total hip arthroplasty. Journal of Arthroplasty. 2013 Feb;28(2): 315-322.e2. Vasanth LC, Pavlov H, Bykerk V. Imaging of rheumatoid arthritis. Rheumatic Disease Clinics of North America. 2013 Aug;39(3):547-66. Viall CA, Chen Q, Liu B, Hickey A, Snowise S, Salmon JE, Stone PR, Chamley LW. Antiphospholipid antibodies internalised by human syncytiotrophoblast cause aberrant cell death and the release of necrotic trophoblast debris. Journal of Autoimmunity. 2013 Sep 12. [Epub ahead of print] Villeneuve E, Nam JL, Bell MJ, Deighton CM, Felson DT, Hazes JM, McInnes IB, Silman AJ, Solomon DH, Thompson AE, White PH, Bykerk VP, Emery P. A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis. Postgraduate Medical Journal. 2013 Apr;89(1050): 231-40. Villeneuve E, Nam JL, Bell MJ, Deighton CM, Felson DT, Hazes JM, McInnes IB, Silman AJ, Solomon DH, Thompson AE, White PH, Bykerk VP, Emery P. A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis. Annals of the Rheumatic Diseases. 2013 Jan;72(1):13-22. Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S, Cadossi R, Goldring MB, Borea PA, Varani K. Pulsed electromagnetic fields increased the anti-inflammatory effect of A2A and A3 adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS One. 2013 May 31;8(5):e65561.

Vukelic M, Qing X, Redecha P, Koo G, Salmon JE. Cholinergic receptors modulate immune complex-induced inflammation in vitro and in vivo. Journal of Immunology. 2013 Aug 15;191(4):1800-07. Walters HM, Aguiar CL, Macdermott EJ, Adams A, Barinstein L, Dayton JD, Salvatore C, Thimmappa N, Lehman TJ. Takayasu arteritis presenting in the context of active tuberculosis: a pediatric case. Journal of Clinical Rheumatology. 2013 Sep;19(6):344-47. Wang W, Wei S, Luo M, Yu B, Cao J, Yang Z, Wang Z, Goldring MB, Chen J. Oxidative stress and status of antioxidant enzymes in children with Kashin-Beck disease. Osteoarthritis Cartilage. 2013 Nov;21(11):1781-89. Xie G, Roshandel D, Sherva R, Monach PA, Lu Y, Kung T, Carrington K, Zhang SS, Pulit SL, Ripke S, Carette S, Dellaripa PF, Edberg JC, Hoffman GS, Khalidi N, Langford CA, Mahr AD, St Clair EW, Seo P, Specks U, Spiera RF, Stone JH, Ytterberg SR, Raychaudhuri S, de Bakker PI, Farrer LA, Amos CI, Merkel PA, Siminovitch KA. Granulomatosis with polyangiitis (Wegener’s) is associated with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. Arthritis & Rheumatism. 2013 Sep;65(9):2457-68. Yarilina A, Xu K, Chan C, Ivashkiv LB. Regulation of inflammatory responses in tumor necrosis factor-activated and rheumatoid arthritis synovial macrophages by JAK inhibitors. Arthritis & Rheumatism. 2012 Dec;64(12):3856-66. Yazici Y, Gibofsky A. The times they are a changin’. Rheumatology (Oxford). 2013 Jan;52(1):3-4. Zhao R, Wang A, Hall KC, Otero M, Weskamp G, Zhao B, Hill D, Goldring MB, Glomski K, Blobel CP. Lack of ADAM10 in endothelial cells affects osteoclasts at the chondro-osseus junction. Journal of Orthopaedic Research. 2013 Sep 21. [Epub ahead of print]

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Division of Rheumatology/ Department of Medicine Physician-in-Chief, Director, Department of Medicine, and Chair, Division of Rheumatology Mary K. Crow, MD, MACR 212.606.1397 Perioperative Medicine Division Linda A. Russell, MD 212.606.1305 Rheumatology Faculty Practices Theodore R. Fields, MD, FACP 212.606.1286 Rheumatology Fellowship Program Anne R. Bass, MD, FACP 212.774.2189 Pediatric Rheumatology Fellowship Program Alexa B. Adams, MD 212.774.2083 HSS Academy of Rheumatology Medical Educators Stephen A. Paget, MD, FACP, MACR 212.606.1845 Directors, Centers of Excellence Inflammatory Arthritis Vivian P. Bykerk, MD 212.774.7520 Lupus and Antiphospholipid Syndrome Jane E. Salmon, MD 212.606.1422 Scleroderma, Vasculitis, and Myositis Robert F. Spiera, MD 212.774.2048 Bone Health and Osteoporosis Linda A. Russell, MD 212.606.1305 Pediatric Rheumatology Thomas J.A. Lehman, MD, FAAP 212.606.1151

The 2013 Annual Report of the Division of Rheumatology is produced by Education & Academic Affairs of Hospital for Special Surgery. Laura Robbins, DSW Senior Vice President Education & Academic Affairs Designated Institutional Officer, GME Marcia Ennis Director Education Publications & Communications

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