2008-2009 HSS Rheumatology Division Annual Report

DIVISION OF RHEUMATOLOGY 2008-2009 ANNUAL REPORT INSIGHTS AND INNOVATIONS

CONTENTS Leadership Report

2

Systemic Lupus Erythematosus

6

Rheumatoid Arthritis, Spondyloarthropathy and Uveitis

10

Vasculitis and Scleroderma

13

Osteoarthritis

15

Metabolic Bone Disease and Orthopaedic Bone Health

17

Pediatric Rheumatology

18

Professional Staff

19

2008-2009 Notable Achievements

21

2008-2009 Selected Publications

24

On the cover: (Left to right) Robert F. Spiera, MD, Director, Vasculitis and Scleroderma Program; Lionel B. Ivashkiv, MD, Associate Chief Scientific Officer, and Carl P. Blobel, MD, PhD, Program Director, Arthritis and Tissue Degeneration Program; and Lisa A. Mandl, MD, MPH, Co-Director of the Center for Education and Research on Therapeutics grant, exemplify the importance of the Hospital’s integrated program of medicine and science.

On this page: Translating basic findings into new ways of treating musculoskeletal conditions and autoimmune diseases is at the heart of Hospital for Special Surgery’s mission. At HSS, scientists such as Lionel B. Ivashkiv, MD, (top) and clinicians such as Linda A. Russell, MD, work closely together, bringing clinical questions into the laboratory and applying basic science discoveries in a meaningful way to help patients.

DIVISION OF RHEUMATOLOGY 1. Dr. Ora Singer 2. Dr. Diana A. Yens 3. Dr. Robert F. Spiera 4. Dr. Steven K. Magid 5. Dr. George Kalliolias 6. Dr. Hendricks H. Whitman III 7. Dr. Richard Stern 8. Dr. Thomas J.A. Lehman 9. Dr. Doruk Erkan 10. Dr. Susan M. Goodman 11. Dr. C. Ronald MacKenzie 12. Dr. Dalit Ashany 13. Dr. Lisa A. Mandl 14. Dr. Alexa B. Adams 15. Dr. Inez Rogatsky 16. Dr. Juliet B. Aizer 17. Dr. Aruni Jayatilleke 18. Dr. Diana Goldenberg 19. Dr. Emma Jane MacDermott 20. Dr. Danieli C. Andrade 21. Dr. L. Nandini Moorthy 22. Dr. Jessica R. Berman 23. Dr. Richard S. Bockman

6 4

3

5

1

8

2

24 22 23

20 18 17 19

21

38 31

33

35 36

37

34 32

INSIGHTS AND INNOVATIONS DIVISION OF RHEUMATOLOGY

Patient Care • Growth and expansion of the Hospital’s Center for Musculoskeletal Perioperative Medicine and the Hospitalist Program • Opening of the Center for Inflammatory Arthritis and Innovative Biologic Therapy and the Mary Kirkland Center for Lupus Care • Initiation of the Cardiovascular Disease Prevention Program

24. Dr. Sergio Schwartzman 25. Dr. Harry Bienenstock 26. Dr. Bento R. Mascarenhas 27. Dr. Lawrence J. Kagen 28. Dr. Laura V. Barinstein 29. Dr. Beverly Johnson 30. Dr. Lindsy Forbess 31. Dr. Kun Chen 32. Dr. Sabeen Anwar 33. Dr. Weijia Yuan 34. Dr. Edward J. Parrish 35. Dr. Stephen J. DiMartino 36. Dr. Charis F. Meng 37. Dr. Joseph A. Markenson 38. Dr. Allan Gibofsky 39. Dr. Stephen A. Paget 40. Dr. Jane E. Salmon 41. Dr. Theodore R. Fields 42. Dr. Michael D. Lockshin 43. Dr. Anne R. Bass 44. Dr. Carol A. Mancuso 45. Dr. Linda A. Russell 46. Dr. Alana Levine

7 9

11

12

10

13 14 16

25

15

26

27

29 30

28 39

41

46

42

44 43

40 45

Clinical Advances • Evaluating the role of rituximab in the treatment of ANCA-related vasculitides • Determining the efficacy of Gleevec® in scleroderma • New therapeutic targets in osteoarthritis • New and effective treatment regimens for refractory pediatric autoimmune disorders

Research • Uncovering the role of interferon alpha in SLE, rheumatoid arthritis and scleroderma • The promise of the PROMISSE study in defining risk factors for pregnancy loss in patients with SLE and antiphospholipid syndrome • Vascular endothelial cell genetic analysis as an approach to defining causes of premature atherosclerosis

OUR MISSION

The mission of the Division of Rheumatology, first and foremost, is to enhance the quality of life for the thousands of patients who come to Hospital for Special Surgery each year seeking our care. This is made possible by a seamless integration of medicine, science, and education that enables us to continually identify clinical challenges, carry out the studies that will help us develop better methods of treatment, facilitate the application of therapeutic advances to the patient care setting, and engage new and seasoned physicians and researchers in unparalleled fellowship training and continuing medical education opportunities.

Our unwavering commitment to this mission will help ensure that adults and children with musculoskeletal and autoimmune disorders receive the best possible care here and everywhere.

LEADERSHIP REPORT

Dear Colleague:

Stephen A. Paget, MD

Mary K. Crow, MD

We are proud to bring you the 2008-2009 Annual Report of the Division of Rheumatology at Hospital for Special Surgery. As members of the professional staff of the largest musculoskeletal specialty hospital in the world, our dedication is to nothing less than assuring a longer and better life for our patients. To achieve that end, our clinicians and scientists are provided with significant opportunities for advancing patient care, education, and research in the field.

Enhancing Care for Patients

Recently, we introduced two new programs—the Mary Kirkland Center for Lupus Care and the Center for Inflammatory Arthritis and Innovative Biologic Therapy—to enhance our ability to provide disease-focused care for specific populations. You will read more about these programs on the pages that follow.

During the past year, physicians in the Hospital’s Division of Rheumatology served as the musculoskeletal perioperative specialists for over 12,000 orthopaedic surgery patients. The Hospital’s Center for Musculoskeletal Perioperative Medicine, directed by rheumatologist C. Ronald MacKenzie, MD, and anesthesiologist Michael K. Urban, MD, PhD, assures the best outcomes for our orthopaedic surgery patients – many of whom present with complex clinical issues.

Rheumatologist Steven K. Magid, MD, played a leadership role during the Hospital’s development and implementation of a new quality review infrastructure, which set in place mechanisms to allow better alignment of strategic goals, sharing of information, and the setting of benchmarks and metrics.

Theodore R. Fields, MD, Clinical Director of the Early Arthritis Initiative, serves as Co-Chairman of the Hospital’s Web Committee and Director of the HSS Rheumatology Website, which has over 800 articles and a large number of videos, audio material, podcasts, and online CME programs. The Rheumatology Website attracts 280,000 unique users a month. Dr. Fields also chairs the Hospital’s CliniCIS Content Board responsible for reviewing changes and improvements to the Computerized Prescriber Order Entry system, including computerized alerts to physicians to improve practice and built-in safety elements such as making it simple to order blood levels when certain antibiotics are prescribed.

2

Reinforcing Our Research Efforts From research innovations that arise in our basic science laboratories to therapeutic insights that develop from collaborations at the translational and clinical levels, the Division of Rheumatology maintains a steadfast commitment to finding solutions in the laboratories and at the bedside for complex clinical problems. In fact, the translation of basic and clinical research findings into applications for medical care is a hallmark of Special Surgery’s “bedside-to bench-to-bedside” approach.

We are pleased to report that in an era in which the National Institutes of Health had less available funds to provide for research, HSS increased its federal grant portfolio by 14.6 percent over 2007, with awards totaling $22.4 million. Total active awards for 2008 totaled $32.7 million, an increase of 14.2 percent or $4.1 million over the previous year.

With this level of support, our clinicians and scientists are able to continue their groundbreaking research, which includes studies in: Systemic Lupus Erythematosus • the innate immune response and the genetic, environmental, and immune mechanisms that contribute to activation of the type 1 interferon pathway • biomarkers to predict disease flare • predictors of pregnancy outcomes • drug trials for difficult-to-treat antiphospholipid syndrome patients and patients who are antiphospholipid antibody positive Rheumatoid Arthritis • role of cytokines in inflammation • relationship of tumor necrosis factor and type 1 interferon to immune system function • mechanisms of joint destruction Osteoarthritis • collagen remodeling in osteoarthritis • protein targets in osteoarthritis disease onset and progression • mechanisms of induction of inflammation • preserving cartilage following injury Vasculitis and Scleroderma • phase IIa trial of imatinib (Gleevec®) in the treatment of diffuse systemic sclerosis • high-dose immunosuppressive therapy in autologous stem cell transplant as a treatment for severe systemic sclerosis • type 1 interferon action in scleroderma • rituximab for ANCA-associated vasculitis

(Top) C. Ronald MacKenzie, MD, and his colleagues are responsible for the pre- and post-operative consultation and care of surgical patients. (Middle) Steven K. Magid, MD, founded the Clinical Informatics Committee of the Medical Board to promote clinician involvement in the Hospital’s clinical informatics initiatives. (Bottom) Theodore R. Fields, MD, plays a key role in the Hospital’s Computerized Prescriber Order Entry system.

3

By closely aligning research and clinical priorities, we can expedite the application of new therapies to the treatment of patients with musculoskeletal and autoimmune diseases.

Hospital for Special Surgery Research Institute 2008 Active National Institutes of Health Awards

Other NIH Awards

40

Total NIH Rheumatology Awards

33

Metabolic Bone Disease and Orthopaedic Bone Health • methods to enhance bone formation and regeneration in arthritis patients • mechanisms of tissue destruction in periodontitis • use of anticatabolic drugs to treat new fractures Pediatric Rheumatology • systematic use of cyclophosphamide and rituximab in a new protocol for children with severe SLE • evaluation of the use of a similar regimen of cyclophosphamide and rituximab for children with scleroderma • the role of cytokine gene polymorphisms in conferring risk and protection in juvenile dermatomyositis In 2008, Lionel B. Ivashkiv, MD, Senior Scientist and Director of Basic Research, was appointed Associate Chief Scientific Officer. In this newly created position, Dr. Ivashkiv, who is the David H. Koch Chair in Arthritis and Tissue Degeneration, is charged with developing a long-term strategic plan for basic science research programs; fostering collaborative research among the basic science programs; and enhancing translational research. Dr. Ivashkiv has an outstanding record of NIH funding and has made major contributions to the understanding of inflammatory mechanisms in autoimmune and musculoskeletal disorders.

For the past two years, the Hospital has been moving forward with the integration of its basic, translational, and clinical research efforts to allow us to maintain dynamic cutting-edge programs and sustain our level of scientific excellence into the future.

By closely aligning research and clinical priorities, we can expedite the application of new therapies to the treatment of patients with musculoskeletal and autoimmune diseases. Translational research teams, made up of clinicians and basic scientists, have targeted a number of areas to address, with one of our largest translational research efforts to date focused on systemic lupus erythematosus and complications of the disease related to pregnancy, neurocognitive function, and cardiovascular system.

In addition, the Hospital is participating in a new Clinical and Translational Science Center led by Weill Cornell Medical College. Peggy Crow, MD, Director of Special Surgery’s Autoimmunity and Inflammation Program, is serving as one of two Coordinating Program Directors for the Center, which is funded by a $49 million National Institutes of Health grant.

As the largest provider of musculoskeletal care—with more than 250,000 patient visits for musculoskeletal disorders and autoimmune diseases annually—we are in a pivotal position to be able to document factors that affect patient outcomes. The Hospital currently has more than 30 patient registries ranging from those for very specific conditions, such as basal joint arthritis, to more broad-based databases, such as the Autoimmune Disease Registry and Repository.

4

Our Education Mission Each and every day we carry out our mission to provide exemplary education programs for Weill Cornell medical students and residents, rheumatology fellows, and seasoned physicians who come to HSS to train. In 2008-2009, we had 11 fellows in rheumatic disease and another four fellows in pediatric rheumatology. Our three-year Rheumatology Fellowship Program draws on the clinical and research resources of NewYork-Presbyterian Hospital/Weill Cornell Medical Center, Memorial SloanKettering Cancer Center, and The Rockefeller University. Fellows gain clinical experience at outpatient clinics focused on adult and pediatric rheumatology and a variety of orthopaedic subspecialties. The program emphasizes research into the biological mechanisms of autoimmune, inflammatory, and musculoskeletal disease, and issues pertinent to clinical epidemiology and health services delivery.

On a national level, Anne R. Bass, MD, Program Director of the Division’s Fellowship Training Program, serves as Chairman of the American College of Rheumatology Training Resources Subcommittee of the Committee on Workforce and Training. Her responsibilities include chairing the panel that rewrites the rheumatology in-training exam and managing the Rheumatology Fellowship Match Program. Juliet B. Aizer, MD, MPH, and Jessica R. Berman, MD, Director of Resident Education at HSS, participated in the development of rheumatology education as representatives to the American College of Rheumatology Committee on Education.

Dr. Berman continues to coordinate the yearly ROSCE (Rheumatology Objective Structured Clinical Examination), a citywide assessment tool for evaluating Rheumatology fellows in areas such as professionalism and patient care skills. The last five years of course data demonstrating ROSCE’s validity and usefulness as a unique rating tool will soon be published in Arthritis Care and Research.

Leading the Way Whether members of the Division of Rheumatology are participating in national or global conferences, collaborating with colleagues within the Hospital and around the country, or serving in leadership positions with professional societies or internal Hospital committees, they do so with a commitment to ultimately providing the highest quality of care for patients with musculoskeletal conditions and autoimmune disorders. We hope you enjoy reading about their individual and collaborative accomplishments in the report that follows.

Stephen A. Paget, MD, FACP, FACR Physician-in-Chief and Chairman, Division of Rheumatology

(Top to bottom) Anne R. Bass, MD, Juliet B. Aizer, MD, MPH, and Jessica R. Berman, MD, play key roles at the national level in the development and implementation of education and training programs for rheumatology fellows. Dr. Berman recently received an ACR REF Clinician Scholar Educator Award for her innovative resident educational programs.

Mary (Peggy) K. Crow, MD Director, Rheumatology Research

5

SYSTEMIC LUPUS ERYTHEMATOSUS

PROFESSIONAL STAFF Mary K. Crow, MD Doruk Erkan, MD, MPH Diane A. Goldenberg, MD, MPH Roberta Horton, LCSW, ACSW Suzy Kim, LCSW Kyriakos A. Kirou, MD, FACR Juliette Kleinman, LCSW, ACSW Elizabeth Kozora, PhD Michael D. Lockshin, MD Lillian Mendez Jillian Rose, LMSW Jane E. Salmon, MD Lisa R. Sammaritano, MD Erica Sandoval My-Lan Tran, LCSW

Systemic lupus erythematosus (SLE) is a major focus of the Division of Rheumatology’s clinicians and scientists, who seek to develop new approaches for managing SLE and its complications. Currently, our research efforts include investigations of mechanisms of type 1 interferon pathway activation in SLE; biomarkers involved in the prediction of disease flare; antiphospholipid syndrome and antiphospholipid antibody positive patients; and predictors of pregnancy outcome.

Type 1 Interferon Pathway Our scientists have particular interest in the innate immune response and the genetic, environmental, and immune mechanisms that contribute to activation of the type 1 interferon pathway (including production of interferon-alpha). Interferon-alpha is a cytokine that is typically produced in the setting of viral infection. In systemic autoimmune diseases, such as lupus, we observe increased production of interferonalpha that is associated with increased disease activity and increased production of autoantibodies that target RNA-associated proteins. In studies performed in collaboration with Timothy B. Niewold, MD, a former HSS rheumatology fellow, we have identified that certain lupus-associated genetic variants confer increased production or response to interferon-alpha. Several of the proteins encoded by those genetic variants map to the Toll-like receptor pathway, implicating that molecular pathway in production of interferon.

Additional studies in the Hospital’s laboratory are investigating the characteristics of the stimuli for Toll-like receptor activation. Plasma autoantibodies and their associated DNA or RNA from patients with lupus have been characterized for their capacity to activate the interferon pathway. Our researchers have found that autoantibodies specific for RNA-associated proteins are more active than anti-DNA antibodies in stimulating this pathway. This is consistent with our earlier studies showing an association between those autoantibodies and interferon pathway activation.

We are also investigating the nature of the RNAs that induce interferon.

The compelling support for a central role for interferon-alpha in lupus pathogenesis has led to a new focus on the role of innate immune system activation in the generation of pathogenic mediators. These insights have been extended to translational studies of patients with well-characterized disease activity and clinical manifestations in order to identify informative molecular biomarkers. Our researchers are studying a cohort of lupus patients in order to determine the relationship of fluctuations in interferon pathway activation to flares in disease activity. This study has compiled one of the most complete and well-documented datasets, including several disease activity measures and biologic samples that have been monitored over three years. Chemokines are among the interferon-inducible genes, and new data support an association between the expression of chemokines and both lupus disease activity and organ damage. Longitudinal studies that relate molecular

6

MARY KIRKLAND CENTER FOR LUPUS RESEARCH Stephen A. Paget, MD Mary K. Crow, MD Michael D. Lockshin, MD Jane E. Salmon, MD Co-Directors

Michael D. Lockshin, MD (left), Director, and Doruk Erkan, MD, Associate Director, Barbara Volcker Center for Women and Rheumatic Diseases, are exploring new ways to help patients suffering from antiphospholipid syndrome.

biomarkers to disease activity will be needed to validate these promising data and establish a sensitive measure of change for interventional studies and patient care.

This work is leading to new understanding of lupus pathogenesis and development of biomarkers that might eventually be used to predict disease flares and is contributing to the rationale for drug development programs that involve monoclonal antibodies specific for interferon-alpha.

In 2001, with support from Katherine and Arnold Snider of Rheuminations, Inc., Hospital for Special Surgery inaugurated the Mary Kirkland Center for Lupus Research to further new understanding of the molecular and cellular basis of systemic lupus erythematosus, contribute to the development of new lupus therapies, and improve the lives of patients with lupus. Research projects address disease susceptibility, alterations in immune function, mechanisms of target organ damage, epidemiology, clinical features, and new therapies for lupus.

Antiphospholipid Syndrome and Antiphospholipid Antibody Positive Patients Researchers at Hospital for Special Surgery are involved in multiple clinical trials ranging from mechanistic studies to drug trials for difficult-to-treat antiphospholipid syndrome (APS) patients and patients who are antiphospholipid antibody positive (aPL positive). They continue to pursue the identification of factors that increase the risk of blood clots, which occur when an antibody attaches to an endothelial cell on the vessel wall, triggering reactions that result in clotting. Currently, patients prone to blood clots are given an anticoagulant to prevent this from occurring. Although blood thinners reduce the risk of the antibody attaching to the arterial or venous wall, they do not change the nature of the potentially harmful antibodies or control or prevent renal or cardiac complications.

One clinical trial currently underway through the Hospital’s Barbara Volcker Center for Women and Rheumatic Diseases and in conjunction with the University of Texas Medical Branch Rheumatology Clinic, seeks to address the blood clot and cardiovascular disease challenges of patients with APS and those who are aPL positive. The study is investigating whether a statin drug—traditionally used to lower cholesterol—is beneficial and safe in reducing the risk of cardiovascular disease and blood clots in these patients. The study has also been designed to allow researchers to observe the effects that the medication has on the antibodies.

7

SYSTEMIC LUPUS ERYTHEMATOSUS

In aPL positive patients, clinical manifestations may include low platelet count, anemia, heart valve disease, skin ulcers, kidney small blood vessel clots, and memory problems. Current treatments available for this syndrome have not been satisfactory.

Another clinical trial taking place at HSS is a pilot study evaluating whether rituximab, approved for treatment of non-Hodgkin’s B-cell lymphoma and for certain patients with rheumatoid arthritis, will reduce the signs and symptoms of aPLrelated clinical problems.

The scientific achievements of Jane E. Salmon, MD, particularly in the area of lupus pregnancy, have earned her national and international accolades.

PROMISSE STUDY Patient Registry Enrollment 2003 TO 2009 (as of June 2009) 550 500 450 400

Through these clinical trials, the Hospital’s rheumatologists hope to define new principles of treatment that will improve the lives of patients with APS or who are aPL positive. At the same time, the Division of Rheumatology has launched a cardiovascular disease prevention counseling program for patients with lupus and/or who are aPL positive. Studies have demonstrated that patients with lupus have higher rates of cardiovascular risk factors and cardiovascular events compared to healthy individuals. Furthermore, patients who are persistently positive for aPL are at increased risk for blood clots. The comprehensive program evaluates patients for traditional cardiac risk factors such as blood pressure, blood glucose, cholesterol levels, body mass index, diet and exercise habits, smoking status, as well as for aPL profile, medication usage, and non-traditional and lupus-specific risk factors.

The PROMISSE Study: Predictors of pRegnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus Patients with SLE and/or antiphospholipid antibodies are at increased risk for miscarriage, preeclampsia, and fetal growth restriction—major causes of maternal, fetal, and neonatal morbidity and mortality. The etiology of these conditions remain unknown and therapy is limited.

350 300 250 200 150 100 50

08

09 20

20

6 20 07

20 0

04

20 05

20

20

03

0

In 2008, the National Institutes of Health extended the PROMISSE study, a multicenter effort coordinated by Hospital for Special Surgery, for an additional five years, beginning with $1.4 million for the first year of renewal. This competitive renewal and extension allows the Hospital’s investigators and co-investigators from 11 academic centers across the country to increase patient enrollment to 700—550 patients with aPL antibodies and/or SLE and 150 healthy controls. In addition, they will be able to continue to identify biomarkers that predict poor pregnancy outcome in these patients, elucidate mechanisms of disease, and choose novel therapeutic targets to prevent such outcomes. Further, they will expand the study to examine a broader range of genes and molecular pathways that can affect pregnancy in patients with lupus, and potentially cause miscarriage and preeclampsia in healthy women.

Since the study’s launch in September 2003, the Hospital has been extremely successful in the recruitment of participants for PROMISSE, enrolling 500 patients in this study as of June 1, 2009.

8

Although the primary hypotheses will not be tested until enrollment is near complete, our researchers have harnessed the PROMISSE cohort to accomplish the following: • determined which assay(s) of aPL antibodies are associated with the highest risk of complications to identify predictors of pregnancy outcomes • exploited the well-defined phenotype and the study design of PROMISSE to analyze the severity, frequency, and timing of flares and the fetal outcomes in 198 PROMISSE SLE patients—a group with stable or mildly active disease at conception • initiated studies to examine the prevalence of variants in genes that regulate complement activation As the study continues, PROMISSE will determine in a prospective cohort of pregnant patients: • whether elevations of split products, generated by activation of the alternative or classical complement pathways, predict poor fetal outcome in patients with antiphospholipid antibodies (aPL) and/or SLE • whether the balance of circulating angiogenic and antiangiogenic factors predict poor fetal and/or maternal outcome in patients with aPL antibodies and/or SLE. In addition, basic research is taking place to determine the mediators and mechanisms of aPL antibody-induced pregnancy loss and preeclampsia in animal models. Current work is directed at defining the initiators and effectors of fetal and placental injury to refine targets for treatment within and beyond complement pathways. Pathways identified in the animal studies guide our studies of biomarkers and genetic risk factors in the PROMISSE study. Elucidating the role of specific complement components and downstream effectors and the role of complement activation within the overall inflammatory cascade will provide a basis for developing new therapies, a rationale for choosing among them, and the potential to improve patient outcomes.

Atherosclerosis in SLE Patients Accelerated atherosclerosis has emerged as a significant threat to the health of patients with SLE. Endothelial dysfunction represents the earliest stage of the atherosclerotic process. In collaboration with the Division of Cardiology at Columbia University College of Physicians and Surgeons, we are examining the relationship between endothelial biomarkers of vascular inflammation and atherosclerotic burden in patients with SLE. Our goal is to characterize the gene expression profiles relevant to atherosclerosis and to the interferon pathway in endothelial cells and elucidate the pathways that promote atherosclerosis in SLE using a novel minimallyinvasive approach to sample vein endothelial cells. The ultimate goal is to identify targets for treatment and means to monitor therapies in these at-risk patients.

MARY KIRKLAND CENTER FOR LUPUS CARE Doruk Erkan, MD, MPH, and Kyriakos A. Kirou, MD Clinical Co-Directors Jane E. Salmon, MD Director, Translational Research Pretima Persad, MPH Manager In July 2009, Hospital for Special Surgery established the Mary Kirkland Center for Lupus Care with the ultimate goal of providing a better quality of life for patients with lupus and/or antiphospholipid syndrome.

The Mary Kirkland Center for Lupus Care provides: • comprehensive, multidisciplinary patient assessments • social work evaluation • patient education programs • support programs, including: LupusLine® Charla de Lupus/Lupus Chat® LANtern® Lupus Asian Network SLE Workshop VOICES 60+ • resource referral • cardiovascular disease prevention counseling • access to clinical trials • coordination of all lupus clinical research projects and integration with lupus basic and translational scientists

9

RHEUMATOID ARTHRITIS, SPONDYLOARTHROPATHY AND UVEITIS

PROFESSIONAL STAFF Adena Batterman, MSW, LCSW Theodore R. Fields, MD, FACP Allan Gibofsky, MD, JD, FACP, FCLM Steven R. Goldring, MD Susan M. Goodman, MD Lionel B. Ivashkiv, MD

Scientists and clinicians in the Division of Rheumatology continue to enhance our understanding of rheumatoid arthritis (RA) and spondyloarthropathy through basic research studies and the establishment of comprehensive clinical centers such as the new Center for Inflammatory Arthritis and Innovative Biologic Therapy. The establishment of the new Center not only permits optimal specialized care for patients with inflammatory arthritis but enables and facilitates translational research focusing on important issues that include, for example, the role of cytokines in mediating inflammation and the development and evaluation of novel therapeutic targets to prevent joint destruction.

Dayna Kurtz, LMSW Joseph A. Markenson, MD Dana E. Orange, MD Stephen A. Paget, MD, FACP, FACR Sergio Schwartzman, MD Millicent Stone, MD Lisa C. Vasanth, MD, MS

Understanding Cytokine’s Role in Inflammation In the laboratory of the Arthritis and Tissue Degeneration Program, research centers on how modulating cytokine signaling impacts cell function and gene expression, and the relationship of these changes to the severity of inflammation and related tissue damage. The Hospital’s researchers have shown, for example, that the function of the cytokine interleukin-10 (IL-10), which normally suppresses inflammation, is turned off in rheumatoid arthritis, while in systemic lupus erythematosus, the effective functioning of IL-10 is reprogrammed and contributes to inflammation.

Studies are now underway to further characterize mechanisms that regulate cellular signaling by the Jak-STAT pathway, which is used universally by many cytokines and found in a diversity of cell types. Researchers are studying mechanisms that mediate crosstalk between this and other major signaling pathways, and determining whether modulation or “reprogramming” of cytokine signaling during inflammation affects the balance of cytokine action. In their analysis of cytokine regulation of tissue destruction and remodeling, they have identified mechanisms by which interferons, cytokines at times used to treat autoimmune diseases, suppress tissue destruction and protect against bone loss that predisposes to osteoporosis. This work has resulted in a number of publications in which potential therapeutic targets and mechanisms for treatment of inflammatory and rheumatic diseases have been reported.

The extent of inflammation and rate of associated bone destruction in RA are determined by the balance between inflammatory factors and the mechanisms that oppose inflammation and bone resorption, and promote healing. IL-10 suppresses osteoclast-mediated bone resorption, which results in bone destruction, by inhibiting signaling by RANK, a key receptor required for osteoclast formation and activity.

A study is underway to identify the mechanisms by which IL-10 inhibits RANK signaling with the goal of translating this information into approaches for attenuating inflammation-induced osteoclast-mediated bone destruction.

Exploring the Function of Type 1 Interferon The Hospital’s researchers have discovered that increased levels of type 1 interferon in plasma are associated with beneficial therapeutic responses to tumor necrosis factor

10

The Hospital’s researchers have discovered that increased levels of type 1 interferon in plasma are associated Steven R. Goldring, MD, Chief Scientific Officer (left) and Lionel B. Ivashkiv, MD, Associate Chief Scientific Officer, pursue pacesetting research in rheumatoid arthritis. Dr. Goldring was recently appointed Chairman of the Research Committee of the National Arthritis Foundation and is the only New Yorkbased rheumatologist selected to participate in the American College of Rheumatology Research and Education Foundation program entitled, “Within Our Reach: Finding a Cure for Rheumatoid Arthritis.”

Dr. Ivashkiv was the lead investigator on a study published in the November 14, 2008 issue of Immunity, which identified a potential new therapeutic target that could be used to treat inflammatory disorders, such as rheumatoid arthritis. He recently was awarded his fourth National Institutes of Health RO1 grant.

with therapeutic

(TNF) inhibitor therapy in patients with rheumatoid arthritis. They suspect that in contrast to interferon-alpha, which is widely disseminated and impacts many aspects of immune system function in patients with SLE, in patients with RA, interferon-beta might be a protective factor that is produced predominantly in the inflamed joint and augments the anti-inflammatory effects of TNF inhibitors. They are now looking at the role of interferon-beta as a predictor of response to TNF antagonist therapy in RA. They also are evaluating the effectiveness of switching the specific anti-TNF agent in a cohort of RA patients, and assessing the persistence of response and remission associated with specific TNF antagonists.

in some patients with

responses to tumor necrosis factor (TNF) inhibitor therapy

rheumatoid arthritis.

Identifying Mechanisms of Joint Destruction The mechanism of joint destruction in rheumatoid arthritis, specifically related to osteoclast activity, has been a long-standing interest of Steven R. Goldring, MD, the Hospital’s Chief Scientific Officer. In patients with rheumatoid arthritis, osteoclasts – which usually clear away damaged bone and promote new bone growth and repair – begin to destroy the healthy bone around joints. Little is known about the causes of this role reversal, and treatment options are currently limited. In an effort to discover novel therapeutic targets to prevent joint destruction, Dr. Goldring seeks to determine the genes and signals that activate the osteoclasts to destroy bone. His work in this area led to his selection by the American College of Rheumatology Research and Education Foundation as one of only 15 scientists in the United States to be awarded an Innovative Basic Research grant in recognition of novel research that is expected to change the future treatment of rheumatoid arthritis. Dr. Goldring’s findings could help to prevent irreversible joint damage and disability in patients with RA.

11

RHEUMATOID ARTHRITIS, SPONDYLOARTHROPATHY AND UVEITIS (CONT.)

THE CENTER FOR INFLAMMATORY ARTHRITIS AND INNOVATIVE BIOLOGIC THERAPY Sergio Schwartzman, MD Director

Theodore R. Fields, MD Consultant, Early Arthritis Initiative

Allan Gibofsky, MD, JD, FACP, FCLM Co-Director

Carla Williams Coordinator, Inflammatory Arthritis Center (IAC)

Dana E. Orange, MD Consultant, Translational Medicine Millicent Stone, MD Consultant, Ankylosing Spondylitis

Susan Kim Social Work Coordinator

In 2008, the Hospital established the Center for Inflammatory Arthritis and Innovative Biologic Therapy (IAC) based on “best evidence medicine” with the following intersecting tenets: • to provide comprehensive care to patients with RA and spondyloarthropathies • to educate medical students from the Weill Cornell Medical College, residents from NewYork-Presbyterian Hospital, and fellows and attendings from HSS • to facilitate translational research by enhancing communication between basic science researchers and clinicians and formulate the foundations for clinical research at HSS • to promote basic and clinical collaborations with the pharmaceutical industry and participate in the development of novel therapeutics for patients with inflammatory arthritis

(Top) Sergio Schwartzman, MD, Director, and Allan Gibofsky, MD, JD, Co-Director, are developing the clinical, scientific, and educational goals of the Center for Inflammatory Arthritis and Innovative Biologic Therapy.

As part of its commitment to providing optimal care to patients, the IAC conducts a weekly clinic, followed by a conference involving rheumatology attendings, a radiology attending, medical students, residents, fellows, and social workers in an interdisciplinary discussion of patients with diverse clinical problems so as to highlight evidence-based therapeutic decisions and assessment of outcomes. The Center has developed and implemented a comprehensive computerized registry and a database of patients with rheumatoid arthritis.

Registries in other inflammatory conditions, including ankylosing spondylitis and psoriatic arthritis, are being developed. In addition, the Center serves as a site of the national Consortium of Rheumatology Researchers of North America (CORRONA).

The Early Arthritis Initiative, a component of the IAC, will educate both physicians and patients on the benefits of early diagnosis and treatment of inflammatory arthritis, with an emphasis on the concept of the “window of opportunity;” enroll patients with early inflammatory arthritis in the IAC database; and participate in basic and clinical studies related to early inflammatory arthritis.

Three clinical trials that were incorporated into the IAC are nearing completion, and two new studies are soon to be launched. Proposals for several investigator initiated trials have been submitted on several topics including the use of a new anti-biological agent, certolizumab.

In addition, several national and international database collaborations are being explored. An effort to promote a closer interaction between clinical and basic science research at HSS has been initiated. This translational approach has encompassed several activities, including a project on the characterization of cytokines and dendritic cells in patients with psoriatic arthritis. Two new Fellowship research studies have been proposed that require the facilities of the IAC. As the Center for Inflammatory Arthritis and Innovative Biologic Therapy continues to develop, the primary objectives will be to continue to build the respective registries so as to begin generating hypotheses, research studies, and publications that cross the basic science and clinical platforms.

12

VASCULITIS AND SCLERODERMA

Scleroderma Scleroderma has become a major focus of clinical and translational investigations at Hospital for Special Surgery. This was facilitated by the establishment of the Rudolf Rupert Scleroderma Research Center in 2005. Directed by Robert F. Spiera, MD, the Center created an infrastructure for clinical, translational, and basic research in scleroderma, as well as for community outreach and patient and physician education.

A number of components have matured in the past few years. The scleroderma registry is a prospective, observational, longitudinal database that collects clinical information and biological materials to further basic scientific research and clinical studies of patients with scleroderma. Collaborative work with other scleroderma centers of excellence is ongoing, allowing this resource to be of value to the broader scleroderma research community.

PROFESSIONAL STAFF Robert F. Spiera, MD Director Mary K. Crow, MD Jessica Gordon, MD Kyriakos A. Kirou, MD, FACR

The first and largest single center prospective phase IIa trial of imatinib (Gleevec速), a tyrosine kinase inhibitor, in the treatment of diffuse systemic sclerosis is currently nearing completion under the direction of Dr. Spiera, and in collaboration with Jessica Gordon, MD, a senior rheumatology fellow. An interim analysis suggested acceptable safety and tolerability, but even more exciting has been the strong suggestion of efficacy in terms of improvements in skin thickness, and even preliminarily a suggestion of improvement in indices of lung function. These findings were presented at the American College of Rheumatology Annual Scientific Meeting in 2008, and will be further updated at the 2009 meetings. Studies of skin biopsies from treated patients confirm the clinically measured improvement in skin thickness.

Basic laboratory investigations using skin, serum, and peripheral blood cells from treated patients are ongoing, offering insights into how imatinib (Gleevec速) is work-

Robert F. Spiera, MD, Director of the Vasculitis and Scleroderma Program, is a pioneer in the field of scleroderma research and has made important inroads in the treatment of this challenging disease.

ing in these patients. An extension phase of the study will make up to two years of further treatment available to patients who have completed the one-year trial. In recognition of this work and her outstanding achievements in clinical and translational investigation under the mentorship of Dr. Spiera, Dr. Gordon was awarded a 2009 American College of Rheumatology Distinguished Fellow Award.

An industry-sponsored trial of dasatinib, a broader tyrosine kinase inhibitor, is now underway at the Scleroderma Research Center, examining the safety and efficacy of that agent in treating interstitial lung disease in patients with diffuse systemic sclerosis. The Hospital also continues as a site for the National Institutes of Healthfunded Scleroderma: Cyclophosphamide or Transplantation Trial (SCOT) to evaluate the potential benefit of high-dose immunosuppressive therapy and autologous stem cell transplant as a treatment for severe systemic sclerosis.

The scleroderma registry and Gleevec速 trials have served as a framework for some exciting translational work in scleroderma. Several investigations are ongoing in the laboratory. These include a search for biomarkers in scleroderma by using gene

13

VASCULITIS AND SCLERODERMA

expression analysis with microarray, studies of activation of the MAP kinase signaling cascade in scleroderma, and investigations into the role of type 1 interferon activation in scleroderma. Studies of patients with scleroderma are showing activation of the interferon pathway in those patients who have autoantibodies targeting RNA or RNA-associated proteins, a common feature with our studies in patients with SLE. Additionally, HSS scientists are investigating the mechanism of action of Gleevec® in scleroderma, looking specifically at gene expression correlates of clinical response.

Researchers are also studying the contribution of mediators of angiogenesis in scleroderma patients and have identified a candidate biomarker of pulmonary dysfunction in those patients.

Kyriakos A. Kirou, MD, is pursuing important basic science and clinical studies in scleroderma.

The scleroderma registry and Gleevec trials have

A grant by the Scleroderma Foundation Tristate Chapter is supporting a Scleroderma Program Coordinator who will foster the further development of clinical, educational, and community outreach efforts in scleroderma at Hospital for Special Surgery. In fall 2008, the Hospital hosted the Scleroderma Foundation Tristate Chapter Research Symposium; this past spring, patient education forums were held.

A scleroderma support group meets regularly on site.

®

served as a framework for some exciting translational work in scleroderma.

Vasculitis In the area of vasculitis, the ongoing RAVE (Rituximab for ANCA-associated Vasculitis) study is investigating the effect of rituximab on remission induction in patients with severe ANCA-associated vasculitis, comparing the safety and efficacy of rituximab to conventional therapy with cyclophosphamide. The study has completed enrollment, and analysis of the primary endpoint will be forthcoming shortly. This large multicenter, prospective, randomized, and controlled clinical trial—sponsored by the National Institute of Allergy and Infectious Disease and the Immune Tolerance Network—may be pivotal in defining the state-of-the-art for treatment of severe ANCA-associated vasculitis.

A multicenter international randomized trial exploring the role of plasmapheresis in patients with severe ANCA-associated vasculitis is soon to be initiated. A collaborative effort by the European Vasculitis Study Group and the U.S.-based Vasculitis Clinical Research Consortium, this will be the largest prospective trial in vasculitis.

In 2008, Dr. Spiera chaired the Fourth International Conference on Giant Cell Arteritis and Polymyalgia Rheumatica, which was hosted by Hospital for Special Surgery and brought together internationally renowned thought leaders and experts from 15 countries. Participants discussed both basic science and clinical topics essential to the practitioner caring for patients with these complex disorders and shared their current understanding in the study and treatment of large vessel vasculitis.

14

OSTEOARTHRITIS

At Hospital for Special Surgery, a team of rheumatologists, scientists, orthopaedic surgeons, and bioengineers are focused on the challenge of preventing the premature development of osteoarthritis and examining the role of inflammation, joint mechanics, and genetic influences, as well as the benefits of approaches for enhancing repair of joint tissues after joint injury. Their efforts have been strengthened with the recent creation of the Osteoarthritis (OA) Initiative—an integrated basic, translational, and clinical research program that focuses on identifying risk factors for OA, prevention or reduction of inflammation at the onset of the disease, new medical interventions, and surgical solutions for treatment of OA.

PROFESSIONAL STAFF Mary K. Crow, MD Mary B. Goldring, PhD Steven R. Goldring, MD Howard J. Hillstrom, PhD Lisa A. Mandl, MD, MPH Hollis G. Potter, MD Scott A. Rodeo, MD Peter A. Torzilli, PhD

Basic Research in OA At the basic research level, the Laboratory of Cartilage Biology, directed by Mary B. Goldring, PhD, is investigating mechanisms by which GADD45ß, a stress response signaling molecule involved in cartilage development, and ESE1 (ELF3), an inflammation-induced transcription factor, regulate collagen remodeling during osteoarthritis. Studies using human surgical specimens and mouse models of OA, including unbiased gene, protein, and microRNA profiling, may elucidate how these factors disrupt cartilage homeostasis and lead to the development of targeted therapies that block cartilage damage and promote effective repair. Dr. Goldring serves as the principal investigator for several National Institutes of Health research projects, including a consortium for an R01 grant on a mechanistic study of osteoarthritis; an R01 grant focused on the role of ESE in the development and progression of OA; and a study to identify the protein involved in osteoarthritis disease onset and progression.

The Hospital’s researchers are also interested in defining the mechanisms of induction of inflammation in osteoarthritis. While it has long been believed that OA is primarily due to degeneration of cartilage, more recent work has demonstrated inflammatory infiltrates in the synovial membrane of OA patients. Our researchers are identifying the gene products present in synovial membranes of patients with early OA in order to understand the determinants of inflammation and progression to end-stage disease with the goal of developing new therapeutic approaches.

Riley J. Williams, III, MD

Mary B. Goldring, PhD, Director of the Hospital’s Laboratory of Cartilage Biology, is investigating the mechanisms involved in the development of osteoarthritis.

She is a member of the Board of Directors of the Osteoarthritis Research Society.

Preserving Cartilage in the Knee The arthritic process typically starts with damage to the cartilage surface, which can appear as a small hole or defect. After an initial injury has caused damage to a specific area of the cartilage, there are few options that can repair the damage, which ultimately will lead to the development of osteoarthritis. A multicenter trial led by orthopaedic surgeon Riley J. Williams III, MD, Director of the Hospital’s Institute for Cartilage Repair, is focused on investigating a new minimally invasive alternative for articular cartilage repair in the knee that may provide improved outcomes compared to the current microfracture approach. A small piece of the patient’s healthy cartilage is removed and broken into individual cells, which are grown in a laboratory and then

15

OSTEOARTHRITIS

inserted into a protein matrix. Using the matrix as a scaffold, the cells begin to grow, creating a piece of new cartilage that is then implanted through a small incision into the damaged area, much like a living patch.

It is accepted that whether an anterior cruciate ligament (ACL) rupture is repaired or not, osteoarthritis will develop in the knee five to 15 years after the injury. In the Hospital’s Tissue Engineering, Regeneration, and Repair Program, Peter A. Torzilli, PhD, Program Director, and his colleagues are studying the influence of trauma on the remodeling and repair of articular cartilage. Their studies are designed to determine whether the development of OA after an ACL injury is related to the initial damage to the articular cartilage or whether the progression to OA is secondary to altered kinematics of walking and knee motion.

Examining OA Risk in Children Funding from the Weill Cornell Medical College Clinical and Translational Science Center is supporting a pilot study by Howard J. Hillstrom, PhD, Director of the Leon Root, MD Motion Analysis Laboratory, on lower extremity alignment, gait, and joint pathophysiology in overweight and normal weight children. Obesity presents numerous problems to children including a greater risk of bone deformity and osteoarthritis. There is a growing concern that overweight children may develop OA at younger ages than previous generations.

Evaluating Joint Replacement Surgery (Top) Lisa A. Mandl, MD, MPH, CoDirector of the Center for Education and Research on Therapeutics (CERT) grant, is developing a major database on patients undergoing joint replacement surgery, which will provide vital information for predicting the factors that determine favorable outcomes after joint replacment and identify risk factors that are associated with complications.

(Bottom) Chris Chen, PhD, and Peter A. Torzilli, PhD, are uncovering information that will help explain how an injury leads to the development of osteoarthritis and joint destruction.

16

The Center for Education and Research on Therapeutics (CERT), funded by the Agency for Healthcare Research and Quality, is obtaining outcomes data on the thousands of patients who undergo joint replacement surgery at HSS and supporting clinical studies to determine the patient demographics, surgical techniques, and prosthetic device characteristics associated with improved outcomes in total joint replacement. The comprehensive CERT/HSS Total Joint Replacement Registry has enrolled over 11,000 patients in two years. Data generated from the CERT has led to a new group of safety initiative projects at HSS and the development of eight pilot research studies designed to assess the determinants of favorable outcomes and the economic impact of total joint surgeries.

Pain Relief for Basal Thumb OA A clinical study is underway to determine whether the drug hyaluronan can help patients suffering with basal thumb OA. The goal is to determine if hyaluronan provides better relief than both placebo or cortisone injections. A previous small, open-label trial showed that hyaluronan provided a significant improvement in pain among the 32 participants, leading the researchers to pursue a much larger study.

It has been shown that hyaluronan can work for three to six months in the knee; researchers want to determine how long it will be effective in the thumb.

METABOLIC BONE DISEASE AND ORTHOPAEDIC BONE HEALTH

A consortium of rheumatologists, endocrinologists, orthopaedic surgeons, and scientists at Hospital for Special Surgery is focused on advancing the prevention and treatment options for osteoporosis, Paget’s disease, and related bone disorders.

These clinicians and scientists pursue the common purpose of preserving the quality of bone and enhancing bone healing.

Patients with fractures or individuals undergoing spinal and other types of surgery often require treatments to enhance bone healing or replace or augment damaged bone. Mesenchymal stem cells (MSCs), capable of differentiating into bone-forming osteoblasts in response to the growth factor BMP-2, are a novel biological means to enhance bone formation. Studies are underway to elucidate further understanding of the mechanism by which MSCs are induced to become bone-forming cells. This will potentially lead to the development of new methods to enhance bone formation and regeneration. Our scientists have also identified stromal-derived factor-1 (SDF-1) as a key molecule in bone healing, with the goal of improving healing after fractures.

PROFESSIONAL STAFF Juliet B. Aizer, MD, MPH Richard S. Bockman, MD, PhD Steven R. Goldring, MD Lionel B. Ivashkiv, MD Joseph M. Lane, MD Martin Nydick, MD Linda A. Russell, MD

Lionel B. Ivashkiv, MD, recently received his fourth NIH R01 award, which extends the focus of his work to investigating the mechanisms of tissue destruction in periodontitis. These studies focus on identifying mechanisms that can inhibit the generation of osteoclasts, the cells that cause bone loss. This will provide insights that can be exploited for therapeutic interventions to suppress the bone and tooth destruction associated with periodontitis and other inflammatory conditions. Most recently, HSS investigators, collaborating with researchers from other institutions, have contributed to the discovery of a gene called interferon regulator factor-8 (IRF-8) that is involved in the development of periodontitis, rheumatoid arthritis, and osteoporosis. The study, which was published online August 30, ahead of print in the journal Nature Medicine, could lead to new treatments in the future.

In collaboration with centers across the country, HSS investigators are looking at selected agents, including teraparitide—currently the only agent that is readily available in the United States—to build bone, enhance bone volume and bone synthesis, and improve bone healing. In addition, the use of subcutaneous parathyroid hormone in osteoporosis after failed treatment with bisphosphonates is being evaluated.

Under the direction of Joseph M. Lane, MD, investigators are testing therapeutic agents that target molecules or pathways responsible for bone formation. They are evaluating agents that block the chemicals responsible for interfering with these boneforming pathways—the next step towards developing enhanced bone production.

Through the Hospital’s Seymour Cohn Metabolic Bone Registry, patient data is collected and analyzed to identify methods for preventing and repairing fragility fractures. Based on the initial data, a pilot study is underway to identify possible genes that may contribute to decreased bone quality that create susceptibility to multiple fractures in some patients.

(Top) Rheumatologist Linda A. Russell, MD, looks for osteoporosis in her patients, which can result from medications used to treat RA. (Bottom) Joseph M. Lane, MD, Chief of the Hospital's Metabolic Bone Disease Service, is leading a number of basic and clinical research studies aimed at improving treatment of patients with osteoporosis.

17

PEDIATRIC RHEUMATOLOGY

PROFESSIONAL STAFF Thomas J.A. Lehman, MD, FAAP, FACR, Chief Alexa B. Adams, MD Theresa Lu, MD, PhD Emma Jane MacDermott, MD, MRCPI

The Division of Pediatric Rheumatology at Hospital for Special Surgery is one of the world’s preeminent pediatric rheumatology programs for both patient care and physician education. The key aspect of the Division is its dedication to taking care of children whose diseases are difficult to diagnose or treat. Many of the children cared for have come to Hospital for Special Surgery because they have not been able to get a proper diagnosis or appropriate care elsewhere. The Hospital’s pediatric rheumatologists care for large numbers of children with difficult conditions where “the answers are not in the textbook,” who did not respond to “standard” therapy.

The Division of Pediatric Rheumatology’s dedication to the care of children with complex diseases for whom there is no “textbook answer” has made it a center of excellence not just for New York City or the metropolitan area, but for children from around the world.

The Division has pioneered new therapies that are now widely accepted therapies for children with lupus, juvenile rheumatoid arthritis, uveitis, scleroderma, and dermatomyositis. The faculty continues to work on a number of substantive new projects related to documenting better therapies for children with rheumatic diseases. The two most important are the systematic use of cyclophosphamide and rituximab in a new protocol for children with severe SLE and lupus nephritis. The combination of drugs provides dramatically improved outcomes for these patients with a much lower overall cost in terms of frequency of hospitalization and total amount of both corticosteroids and cyclophosphamide received. We have shown that with less medicine we are getting far better results.

The second major project is an evaluation of the use of a similar regimen of cyclophosphamide and rituximab for children with scleroderma. This study is going well, but because childhood scleroderma is rare, the answers are not yet in.

The Pediatric to Adult Rheumatology Transition Clinic, directed by Alexa B. Adams, MD, is having continued success transitioning our pediatric patients to the adult team as they mature to adulthood. The well-organized transition process puts patients at ease with their new physicians, identifies a designated contact person, and assures the appropriate transfer of information.

(Top) Thomas J.A. Lehman, MD, Chief of Pediatric Rheumatology, has garnered an international reputation for managing some of the most challenging cases in the field. (Bottom) The Division of Pediatric Rheumatology has expanded with the addition of Emma Jane MacDermott, MD, who completed her fellowship in pediatric rheumatology at Hospital for Special Surgery.

18

Hospital for Special Surgery has one of only 18 approved training programs for fellows in pediatric rheumatology and continues to train fellows both from within the United States and around the world. In addition, large numbers of physicians from other countries visit our program for training periods of weeks to months. In the last year, we have trained five physicians from Spain and one each from Israel and Japan. Past graduates of our program are now directing pediatric rheumatology programs in Singapore, Beijing, and Shanghai.

PROFESSIONAL STAFF

DIVISION OF RHEUMATOLOGY Stephen A. Paget, MD, FACP, FACR Physician-in-Chief Chairman, Division of Rheumatology Co-Director, Mary Kirkland Center for Lupus Research Rheumatoid arthritis, SLE, vasculitis Alexa B. Adams, MD Associate Director, Pediatric Rheumatology Fellowship Training Program Pediatrics Juliet B. Aizer, MD, MPH Clinical Scholar Educator Clinical epidemiology, osteoporosis, rheumatoid arthritis, SLE, gout, osteoarthritis Dalit Ashany, MD General rheumatology Anne R. Bass, MD Director, Rheumatology Fellowship Program Lyme disease, thromboembolic disease Jessica R. Berman, MD Director, Resident Education Clinical Scholar Educator General rheumatology Harry Bienenstock, MD General rheumatology Richard S. Bockman, MD, PhD Metabolic bone disease Mary K. Crow, MD Director, Rheumatology Research Co-Director, Mary Kirkland Center for Lupus Research SLE, osteoarthritis, atherosclerosis research, scleroderma research

Gina DelGuidice, MD General rheumatology Stephen J. DiMartino, MD, PhD Myositis, general rheumatology Doruk Erkan, MD, MPH Co-Director, Mary Kirkland Center for Lupus Care Director, Lupus Clinical Trials Consortium Antiphospholipid syndrome, SLE Theodore R. Fields, MD, FACP Director, Rheumatology Faculty Practice Plan Clinical Director, Early Arthritis Initiative Crystalline arthropathies, general rheumatology Jacobo Futran, MD General rheumatology Allan Gibofsky, MD, JD, FACP, FCLM Co-Director, Center for Inflammatory Arthritis and Innovative Biologic Therapy General rheumatology, genetics, rheumatoid arthritis, spondyloarthropathies, Behcet’s disease Steven R. Goldring, MD Chief Scientific Officer Bone biology, rheumatoid arthritis, osteoarthritis, osteolysis research Susan M. Goodman, MD General rheumatology, perioperative care Lionel B. Ivashkiv, MD Associate Chief Scientific Officer Rheumatoid arthritis, SLE research, cytokine, Jak-STAT research Lawrence J. Kagen, MD Myositis, general rheumatology

Kyriakos A. Kirou, MD, FACR Co-Director, Mary Kirkland Center for Lupus Care SLE, progressive systemic sclerosis research Elizabeth Kozora, PhD SLE, antiphospholipid syndrome cognitive function research Thomas J.A. Lehman, MD, FAAP, FACR Chief, Pediatric Rheumatology Pediatrics, SLE, juvenile inflammatory arthritis, psoriatic arthritis Michael D. Lockshin, MD Director, Barbara Volcker Center for Women and Rheumatic Diseases Co-Director, Mary Kirkland Center for Lupus Care SLE, antiphospholipid syndrome, pregnancy Emma Jane MacDermott, MD, MRCPI General pediatric rheumatology, children with juvenile arthritis and systemic autoimmune diseases C. Ronald MacKenzie, MD Co-Director, Center for Musculoskeletal Perioperative Medicine Perioperative care, general rheumatology, ethics Steven K. Magid, MD General rheumatology, information technology Carol A. Mancuso, MD, FACP Clinical epidemiology Lisa A. Mandl, MD, MPH Clinical epidemiology, osteoarthritis, orthopaedic surgery outcomes

19

PROFESSIONAL STAFF

Joseph A. Markenson, MD Rheumatoid arthritis, SLE, clinical trials

Richard Stern, MD General rheumatology

Lionel B. Ivashkiv, MD Laboratory of Osteolysis Research

Bento R. Mascarenhas, MD General rheumatology

Lisa C. Vasanth, MD, MS Clinical epidemiology, early rheumatoid arthritis

Ed Purdue, PhD Laboratory of Steroid Hormone Receptors and Inflammation

Mary Beth Walsh, MD General rheumatology

Inez Rogatsky, PhD Glucocorticoid signaling

Jacqueline M. Mayo, MD Perioperative care Charis F. Meng, MD General rheumatology, acupuncture for musculoskeletal pain, older patients with chronic musculoskeletal pain

AUTOIMMUNITY AND INFLAMMATION PROGRAM

Sonil S. Parr, MD Perioperative care

Arthur M. Yee, MD, PhD General rheumatology, Raynaud’s phenomenon

Mary K. Crow, MD Program Director SLE research, scleroderma research

Edward J. Parrish, MD General rheumatology, HIV

Diana A. Yens, MD General rheumatology

Guillermina Girardi, PhD SLE, antiphospholipid research

RESEARCH DIVISION LEADERSHIP

Kyriakos A. Kirou, MD, FACR SLE, progressive systemic sclerosis research

Steven R. Goldring, MD Chief Scientific Officer Bone biology, rheumatoid arthritis, osteoarthritis, osteolysis research

Theresa Lu, MD, PhD Lymphoid Tissue Organization and Function Laboratory

Jill M. Rieger, MD Perioperative care Linda A. Russell, MD General rheumatology, metabolic bone disease Jane E. Salmon, MD Co-Director, Mary Kirkland Center for Lupus Research SLE, antiphospholipid syndrome research, atherosclerosis, pregnancy Lisa R. Sammaritano, MD SLE, antiphospholipid syndrome, pregnancy Sergio Schwartzman, MD Director, Center for Inflammatory Arthritis and Innovative Biologic Therapy Rheumatoid arthritis, spondyloarthropathy, uveitis Robert F. Spiera, MD Director, Vasculitis and Scleroderma Program and the Rudolf Rupert Scleroderma Research Center Vasculitis, scleroderma

20

Evette Weil, MD Perioperative care

Lionel B. Ivashkiv, MD Associate Chief Scientific Officer Jak-STAT, cytokines Robert N. Hotchkiss, MD Director, Clinical Research Hand orthopaedics

ARTHRITIS AND TISSUE DEGENERATION PROGRAM Carl P. Blobel, MD, PhD Program Director Laboratory of Cellular Signaling and Immune Regulation Xiaoyu Hu, MD, PhD Laboratory of Cytokine Signaling and Inflammation

Carol Mancuso, MD, FACP Clinical epidemiology Stephen A. Paget, MD, FACP, FACR Rheumatoid arthritis, SLE Alessandra Pernis, MD SLE, cytokine regulation Lisa R. Sammaritano, MD SLE, antiphospholipid syndrome, pregnancy Jane E. Salmon, MD Inflammatory Effector Mechanisms Laboratory, SLE, antiphospholipid syndrome, atherosclerosis, pregnancy

2008-2009 NOTABLE ACHIEVEMENTS

Rheumatologists at HSS are regularly cited for their professional achievements and outstanding contributions to patient care, research,

AWARDS AND SPECIAL RECOGNITION Juliet B. Aizer, MD, MPH Graduate, Harvard Macy Program for Educators in the Health Professions Jessica R. Berman, MD Clinician Scholar Educator Award, American College of Rheumatology

and education. They hold leadership positions and are on numerous committees of national and international organizations and professional societies, and serve as editors and on editorial boards of the major peer-reviewed journals in the field.

Richard S. Bockman, MD, PhD Under Dr. Bockman’s mentorship, Amanda Carmel, MD, received a Mary and David Hoar Fellowship in the Prevention and Treatment of Hip Fracture Mary K. Crow, MD Katherine Swan Ginsburg Visiting Professor, Brigham and Women’s Hospital, Boston Kroc Visiting Professor, UCLA Invited Lecturer, Royal College of Physicians of Ireland Invited Lecturer, Annual Meeting, Oligonucleotide Therapeutics Society Kare Berglund Lecture, Lund University, Sweden Visiting Professor and Speaker, Medical Grand Rounds, Emory University School of Medicine Featured Lecturer, Annual Scientific Meeting, American College of Rheumatology Plenary Lecturer, International Cytokine Society in Montreal, Canada Doruk Erkan, MD, MPH Lupus Research Award, New York Community Trust Rudd-Gardy Teaching Excellence Award, Division of Rheumatology, Hospital for Special Surgery Speaker, Meet the Professor Session: Antiphospholipid Syndrome, Annual Scientific Meeting, American College of Rheumatology

Invited Speaker, First National Thrombotic Storm Meeting Allan Gibofsky, MD, JD, FACP, FCLM Reappointment as Special Consultant to the Arthritis Advisory Committee of the Food and Drug Administration Mary B. Goldring, PhD Alumni Achievement Award, Robert D. Clark Honors College, University of Oregon Steven R. Goldring, MD Visiting Scholar, 2008 Annual Clinical Research Symposium, University of Michigan Medical School’s Clinical and Translational Science Center, the Michigan Institute for Clinical and Health Research Visiting Professor in Rheumatology, University of Pittsburgh Medical School Paul Klemperer Award, New York Academy of Medicine Arthur C. DeGraff Invited Speaker, Department of Medicine Annual Research Day, NYU School of Medicine Recipient, ACR-REF Within Our Reach Innovative Grant Plenary Speaker, European Society of Clinical Investigation, Geneva, Switzerland Speaker and Session Chair, Segal North American Workshop on Osteoarthritis Thomas J.A. Lehman, MD, FAAP, FACR Distinguished Visiting Expert, Ministry of Health of the Government of Singapore Michael D. Lockshin, MD Morris Ziff Distinguished Lecturer in Rheumatology, Southwestern Medical Center, Dallas Pfizer Visiting Professor, Louisiana State University Invited Speaker, EuroLupus Project Meeting

21

2008-2009 NOTABLE ACHIEVEMENTS

Michael D. Lockshin, MD (cont.)

Invited Speaker, European League Against Rheumatism (EULAR), Paris, France Session Co-chair, Fourth International Neuroendocrine Immunology in Rheumatic Disease Conference, Santa Margherita, Italy Invited Speaker, Ninth International Conference on Systemic Lupus Erythematosus, Vancouver (2010) Jane E. Salmon, MD Elected to Association of American Physicians Pfizer Visiting Professor, University of Kentucky Presenter, Research Lecture, 30th Year Reunion Class, Columbia University College of Physicians and Surgeons Speaker, Seventh European Lupus Congress, Amsterdam Lisa R. Sammaritano, MD Faculty, Antiphospholipid Syndrome, Rheumatology Review, Course, Harvard Medical School Faculty, Update Your Medicine: Antiphospholipid Syndrome, Weill Cornell Medical College Faculty, Updates in Rheumatology (ACINDES): Systemic Lupus Erythematosus; Antiphospholipid Syndrome, Madrid, Spain Faculty, 2009 Update: Antiphospholipid Syndrome, ACR Clinical Symposium, Annual Scientific Meeting, American College of Rheumatology Robert F. Spiera, MD Under Dr. Spiera’s mentorship, Dr. Jessica Gordon, senior rheumatology fellow, was awarded the 2009 American College of Rheumatology Distinguished Fellow Award

22

LEADERSHIP POSITIONS Alexa B. Adams, MD Member, Pediatric Scholarly Oversight Committee, NewYork-Presbyterian Hospital/Weill Cornell Medical Center Juliet B. Aizer, MD, MPH Fellow Representative, American College of Rheumatology Committee on Education Scholar Educator, Margaret and Ian Smith Clinical Skills Center, Weill Cornell Medical College Relevance Reviewer, Rheumatology Subspecialty Examination, American Board of Internal Medicine Anne R. Bass, MD Chairman, Training Resources Subcommittee of the Committee on Workforce and Training, American College of Rheumatology Jessica R. Berman, MD Core Faculty Member in Teaching and Coordinator, Subspecialty Education in Rheumatology, NewYork-Presbyterian Hospital/Weill Cornell Medical Center Member, Subcommittee on Resident Education, American College of Rheumatology Richard S. Bockman, MD, PhD Member, Professional Practice Committee, American Society for Bone and Mineral Research Mary K. Crow, MD President, Henry Kunkel Society Chair, Scientific Advisory Board, Alliance for Lupus Research Member, Study Section, Autoimmunity Centers of Excellence, National Institute of Allergy and Infectious Diseases Member, Special Emphasis Panel Review Committee, National Institutes of Health

Doruk Erkan, MD, MPH Member, Thrombotic Storm Classification Committee, First National Thrombotic Storm Meeting Theodore R. Fields, MD, FACP Member, Abstract Selection Committee: Quality Measures and Innovations in Practice Management and Care Delivery, American College of Rheumatology Allan Gibofsky, MD, JD, FACP, FCLM Executive Vice President and Member, Executive Committee, Consortium of Rheumatology Researchers of North America (CORRONA) Member, Executive Committee, International Consensus Program on Rheumatoid Arthritis Secretary-Treasurer, The New York Rheumatism Association Mary B. Goldring, PhD U.S. Section Head, Cartilage Biology and Osteoarthritis: Faculty of 1000 Medicine, Rheumatology and Clinical Immunology Board Member, Osteoarthritis Research Society International (OARSI) Steven R. Goldring, MD Chairman, Research Committee, National Arthritis Foundation Chairman, Basic Science Symposia Planning Committee, Annual Scientific Meeting, American College of Rheumatology Member, Nominations and Appointments Committee, American College of Rheumatology Program Organizer, Segal North American Workshop on Osteoarthritis Co-organizer, Rheumatology Fellows Research Workshop, American College of Rheumatology Member, Organizing Committee, Second International Conference on Osteoimmunology, Rhodes, Greece

Thomas J.A. Lehman, MD, FAAP, FACR Member, Medical and Scientific Committee, Lupus Foundation of America Michael D. Lockshin, MD Member, Organizing Committees: European League Against Rheumatism (EULAR), Copenhagen, 2009; European Workshop for Rheumatology Research (EWRR), Warsaw, 2009; the Sixth International Conference on Gonadal Hormones, Pregnancy and Rheumatic Diseases, Lausanne, 2009; and the 13th International Congress on Antiphospholipid Antibodies, Galveston, 2010.

Steven K. Magid, MD Member: Chief Medical Information Officer Leadership Group, DVT/VTE Academic Collaboration, and Outcomes Advisory Board, Eclipsys Member, Medical Informatics of New York Member, Practice Improvement Module Development Committee and Quality of Care Subcommittee, American College of Rheumatology Lisa A. Mandl, MD, MPH Member, Epidemiology Abstract Review Committee, Annual Meeting, American College of Rheumatology Jane E. Salmon, MD Member, Scientific Programme Committee, European League Against Rheumatism (EULAR) Participant, Roundtable on Arthritis and Rheumatic Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Robert F. Spiera, MD President, New York Rheumatism Association Medical Advisory Board, Vasculitis Foundation Co-Chair, Medical and Scientific Advisory Board, Scleroderma Tri-State Chapter

EDITORIAL APPOINTMENTS

Michael D. Lockshin, MD Editor-in-Chief, Arthritis & Rheumatism Jane E. Salmon, MD Co-editor, Arthritis & Rheumatism Robert F. Spiera, MD Advisory Editor, Arthritis & Rheumatism Editorial Board, Rheumatology News

Juliet B. Aizer, MD, MPH Reviewer, Lupus Mary K. Crow, MD Associate Editor, Annals of Rheumatic Diseases Doruk Erkan, MD, MPH Advisory Editor, Arthritis & Rheumatism Theodore R. Fields, MD, FACP Reviewer: Arthritis & Rheumatism, Arthritis Care and Research Mary B. Goldring, PhD Associate Editor, Journal of Cellular Physiology Co-Editor, Arthritis & Rheumatism Associate Editor, Biochimica et Biophysica Acta: Molecular Basis of Disease Member, Board of Associate Editors, Journal of Orthopaedic Research Associate Editor, Arthritis Research & Therapy Thomas J.A. Lehman, MD, FAAP, FACR Associate Editor, Arthritis & Rheumatism Section Editor, Up to Date, Pediatric Rheumatology Section Editor, Current Rheumatology Reports, Pediatric Rheumatology Author, A Clinician's Guide to Rheumatic Diseases in Childhood (Oxford University Press)

23

2008-2009 SELECTED PUBLICATIONS

METABOLIC BONE DISEASE AND ORTHOPAEDIC BONE HEALTH Aizer J, Reed G, Harrison MJ. Predictors of bone density testing in patients with rheumatoid arthritis. Rheumatology International (In press).

Bilezikian JP, Matsumoto T, Bellido T, Khosla S, Martin J, Recker RR, Heaney R, Seeman E, Papapoulos S, Goldring SR. Targeting bone remodeling for the treatment of osteoporosis: summary of the proceedings of an ASBMR workshop.

Journal of Bone and Mineral Research 2009 Mar; 24(3):373-85.

Cipriano CA, Issack PS, Shindle L, Werner CM, Helfet DL, Lane JM. Recent Advances Toward the Clinical Application of PTH (1-34) in Fracture Healing. HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery 2009 Mar 17. [Epub ahead of print].

Gehrig LM, Collinge C, Kaufman J, Lane JM, O'Connor MI, Tosi LL. Osteoporosis: management and densitometry for orthopaedic surgeons. Instructional Course Lectures 2009; 58:805-15.

Gehrig LM, Lane JM, O’Connor MI. Osteoporosis: management and treatment strategies for orthopaedic surgeons. Instructional Course Lectures 2009; 58:817-32.

Lenart BA, Neviaser AS, Lyman S, Chang CC, Edobor-Osula F, Steele B, van der Meulen MC, Lorich DG, Lane JM. Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study. Osteoporosis International 2009 Aug; 20(8):1353-62. [Epub 2008 Dec 9].

Nieves JW, Bilezikian JP, Lane JM, Einhorn TA, Wang Y, Steinbuch M, Cosman F. Fragility fractures of the hip and femur: incidence and patient characteristics. Osteoporosis International 2009 May 30.

[Epub ahead of print].

Papadopoulos EC, Edobor-Osula F, Gardner MJ, Shindle MK, Lane JM. Unipedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures: early results.

Journal of Spinal Disorders & Techniques 2008 Dec; 21(8):589-96.

Steele B, Serota A, Helfet DL, Peterson M, Lyman S, Lane JM. Vitamin D deficiency: A common occurrence in both high-and low-energy fractures. HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery 2008 Sep; 4(2):143-8.

OSTEOARTHRITIS Dugar A, Farley ML, Wang AL, Goldring MB, Goldring SR, Swaim BH, Bierbaum BE, Burstein D, Gray ML. The effect of paraformaldehyde fixation on the delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) measurement. Journal of Orthopaedic Research 2008; 4:279-286.

Goldring SR. Needs and opportunities in the assessment and treatment of osteoarthritis of the knee and hip: the view of the rheumatologist. The Journal of Bone and Joint Surgery (Am) 2009 Feb; 91 Suppl 1:4-6.

Goldring SR. Role of bone in osteoarthritis pathogenesis.

Medical Clinics of North America 2009 Jan; 93(1):25-35, xv.

Goldring SR. The role of bone in osteoarthritis pathogenesis.

Rheumatic Disease Clinics of North America 2008; 34(3):561-71.

Goodwin JL, Farley ML, Swaim B, Goldring SR, Goldring MB, Bierbaum BE, Gray ML. Dual proline labeling protocol for individual “baseline” and “response” biosynthesis measurements in human articular cartilage. Osteoarthritis and Cartilage 2008; 16:1263-1266.

Gross KD, Hillstrom H. Knee osteoarthritis: primary care using noninvasive devices and biomechanical principles. Medical Clinics of North America 2009 Jan; 93(1):179-200, xii.

Gross KD, Hillstrom HJ. Noninvasive devices targeting the mechanics of osteoarthritis. Rheumatic Disease Clinics of North America 2008 Aug; 34(3):755-76. Review.

Hamamura K, Goldring MB, Yokota H. Involvement of p38 MAPK in regulation of MMP13 mRNA in chondrocytes in response to surviving stress to endoplasmic reticulum.

Archives of Oral Biology 2009; 54:279-86.

Ijiri K, Zerbini LF, Peng H, Otu HH, Tsuchimochi K, Otero M, Dragomir C, Walsh N, Bierbaum BE, Mattingly D, van Flandern G, Komiya S, Aigner T, Libermann TA, Goldring MB. Differential expression of GADD45b in normal and osteoarthritic cartilage: potential role in homeostasis of articular chondrocytes.

Arthritis & Rheumatism 2008; 58:2075-2087.

Luan Y, Kong L, Howell DR, Ilalov K, Fajardo M, Bai XH, Di Cesare PE, Goldring MB, Abramson SB, Liu CJ. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin.

Osteoarthritis and Cartilage 2008; 16:1413-1420.

Mandl LA, Hotchkiss R, Adler R, Lyman S, Daluiski A, Wolfe S, Katz J. Injectable hyaluronan for the treatment of carpometacarpal osteoarthritis: an open label pilot trial. Current Medical Research and Opinion. (In press).

24

Scanzello CR, Moskowitz N, Gibofsky A: The post-NSAID era: what to use now for the pharmacologic treatment of pain and inflammation in osteoarthritis. Current Rheumatology Reports 2008; 10:49-56.

Moorthy, LN, Peterson MGE, Hassett AL, Baratelli M, Chalom EC, Hashkes PK, Hong S, Reiff A, Lehman TJA. Relationship between health-related quality of life and SLE activity and damage in children over time. Lupus 2009; 18:622-29.

Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis (OA): is OA a chronic wound?

Current Opinion in Rheumatology 2008; 20:565-72.

Moorthy LN, Peterson MGE, Onel KB, Lehman TJA. Do children with lupus have fewer male siblings? Lupus 2008; 17:128-31.

Scanzello CR, Umoh E, Pessler F, Diaz-Torne C, Miles T, Dicarlo E, Potter HG, Mandl L, Marx R, Rodeo S, Goldring SR, Crow MK. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease.

Osteoarthritis and Cartilage 2009 Aug; 17(8):1040-8. [Epub 2009 Mar 6].

Wang TM, Yen HC, Lu TW, Chen HL, Chang CF, Liu YH, Tsai WC. Bilateral knee osteoarthritis does not affect interjoint coordination in older adults with gait deviations during obstacle-crossing. Journal of Biomechanics 2009 Aug 11. [Epub ahead of print].

Yen HC, Chen HL, Liu MW, Liu HC, Lu TW. Age effects on the inter-joint coordination during obstacle-crossing. Journal of Biomechanics 2009 Aug 6. [Epub ahead of print].

PEDIATRIC RHEUMATOLOGY Adams AB, Lehman TJA. Adalimumab therapy for childhood uveitis: a case report. International Journal of Advances in Rheumatology 2008; 6(1).

Angeles-Han S, Flynn T, Lehman TJA. Abatacept for refractory juvenile idiopathic arthritis-associated uveitis- a case report.

The Journal of Rheumatology 2008 Sep; 35(9):1897-8.

Barillas-Arias L, Adams A, Lehman TJA. Pediatric vasculitic syndromes: Henoch-Schonlein purpura. Consultant for Pediatricians 2008 Sept;7(9): 361-367.

Lehman, TJA. Are withdrawal trials in paediatric rheumatic disease helpful. Lancet 2008 Aug 2; 372(9636):348-50.

MacDermott EJ, Lehman TJA. The role of gene transcript signature in diagnosing systemic onset juvenile idiopathic arthritis. Current Rheumatology Reports 2008; 10:133-4.

Moorthy LN, Gaur S, Peterson MG, Landa YF, Tandon M, Lehman TJA. Poststreptococcal reactive arthritis in children: a retrospective study. Clinical Pediatrics (Phila) 2009; 48:174-182.

Niewold TB, Adler JE, Glenn SB, Lehman TJA, Harley JB, Crow MK. Age- and sex-related patterns of serum interferon-alpha activity in lupus families. Arthritis & Rheumatism 2008; 58:2113-9.

Patel AM, Lehman TJA. Rituximab for severe refractory pediatric Wegener granulomatosis. Journal of Clinical Rheumatology 2008; 14:278-80.

RHEUMATOID ARTHRITIS AND SPONDYLOARTHROPATHY Belostocki K, Pricop L, Redecha PB, Aydin A, Leff L, Harrison MJ, Salmon JE. Infliximab treatment shifts the balance between stimulatory and inhibitory FcÎłRII isoforms on neutrophils in rheumatoid arthritis patients. Arthritis & Rheumatism 2008; 58:384-388.

Berman J, Krasnokutsky S, Bass A, Fields T, et al. The Fifth Annual New York Rheumatology Objective Structured Clinical Examination (ROSCE): The Trainee Self-Assessment of Professionalism vs. Exam Raters. Arthritis & Rheumatism Supplement, September 2008 (Abstract); Arthritis Care and Research (In press).

Crotti TN, Sharma SM, Fleming JD, Flannery MR, Ostrowski MC, Goldring SR, McHugh KP. PU.1 and NFATc1 mediate osteoclastic induction of the mouse beta3 integrin promoter. Journal of Cellular Physiology 2008; 215(3):636-44.

Crow MK. Anticyclic citrullinated peptide antibody-negative rheumatoid arthritis: clues to disease pathogenesis. Current Rheumatology Reports 2008; 10:165-7.

Dastmalchi M, Grundtman C, Alexanderson H, Mavragani CP, Einarsdottir H, Helmers SB, Elvin K, Crow MK, Nenesmo I, Lundberg IE. A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Annals of the Rheumatic Diseases 2008; 67:1670-7.

Moorthy LN, Peterson MG, Harrison MJ, Onel KB, Lehman TJA. Physical function assessment tools in pediatric rheumatology.

Pediatric Rheumatology Online Journal 2008; 4:6-9.

25

2008-2009 SELECTED PUBLICATIONS

RHEUMATOID ARTHRITIS AND SPONDYLOARTHROPATHY (CONT.) Furst DE, Keystone EC, Kirkham B, Fleischmann R, Meese P, Breedveld FC, Smolen JS, Kalden JR, Burmester GR, Braun J, Emery P, Winthrop K, Bresnihan B, De Benedetti F, Dorner T, Gibofsky A, Schiff MH, Sieper J, Singer N, Van Riel PLCM, Weinblatt ME, Weisman MH: Updated consensus statement on biological agents for the treatment of rheumatic diseases.

Annals of the Rheumatic Diseases 2008; 67s3:2-25.

Gibofsky A, Harrington JT: Pay for performance: will we get the carrot or the stick? Arthritis Care & Research 2008; 9:1203-1206.

Goldring SR. Periarticular bone changes in rheumatoid arthritis: pathophysiological implications and clinical utility. Annals of the Rheumatic Diseases 2009 Mar; 68(3):297-9. Annals of the Rheumatic Diseases 2009 Jun; 68(6):1080.

Ho HH, Antoniv TT, Ji JD, Ivashkiv LB. Lipopolysaccharideinduced expression of matrix metalloproteinases in human monocytes is suppressed by IFN-gamma via superinduction of ATF-3 and suppression of AP-1. The Journal of Immunology 2008 Oct 1; 181(7):5089-97.

Hu X, Chakravarty SD, Ivashkiv LB. Regulation of interferon and toll-like receptor signaling during macrophage activation by opposing feed forward and feedback inhibition mechanisms.

Immunological Reviews 2008 Dec; 226:41-56. Review.

Hu X, Chung AY, Wu I, Foldi J, Chen J, Ji JD, Tateya T, Kang YJ, Han J, Gessler M, Kageyama R, Ivashkiv LB. Integrated regulation of Toll-like receptor responses by notch and interferon-gamma pathways. Immunity 2008 Nov 14; 29(5):691-703. [Epub 2008 Oct 30].

Hu Y, Park-Min KH, Yarilina A, Ivashkiv LB. Regulation of STAT pathways and IRF1 during human dendritic cell maturation

by TNF-alpha and PGE2. Journal of Leukocyte Biology 2008 Nov; 84(5):1353-60. [Epub 2008 Aug 4].

Ivashkiv LB. A signal-switch hypothesis for cross-regulation of cytokine and TLR signalling pathways. Nature Reviews Immunology 2008 Oct; 8(10):816-22.

Ivashkiv LB. Cross-regulation of signaling by ITAM-associated receptors. Nature Immunology 2009 Apr; 10(4):340-7. [Epub 2009 Mar 19]. Review.

Ji JD, Ivashkiv LB. Roles of semaphorins in the immune and hematopoietic system. Rheumatology International 2009 May; 29(7):727-34. [Epub 2009 Jan 13].

Ji JD, Park-Min KH, Ivashkiv LB. Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages. Human Immunology 2009 Apr; 70(4):211-7.

[Epub 2009 Feb 7].

Park-Min KH, Ji JD, Antoniv T, Reid AC, Silver RB, Humphrey MB, Nakamura M, Ivashkiv LB. IL-10 suppresses calcium-mediated costimulation of receptor activator NF-kappaB signaling during human osteoclast differentiation by inhibiting TREM-2 expression.

The Journal of Immunology 2009 Aug 15; 183(4):2444-55. [Epub 2009 Jul 22; PubMed - in process].

Rudominer RL, Roman MJ, Devereux RB, Paget SA, Schwartz JE, Lockshin MD, Crow MK, Sammaritano L, Levine DM, Salmon JE. Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fraction.

Arthritis & Rheumatism 2009 Jan; 60(1):22-9.

Salmon JE, Roman MJ. Subclinical atherosclerosis in rheumatoid arthritis. American Journal of Medicine 2008; 121: S3-8.

Sherber NS, Wigley FM, Paget SA. Diffuse fasciitis with eosinophilia developing after local irradiation for breast cancer.

Clinical Rheumatology 2009 Jun; 28(6):729-32. [Epub 2009 Feb 18.]

Singer O, Gibofsky A: Review of disease modifying antirheumatic drug use in rheumatoid arthritis. International Journal of Advances in Rheumatology 2009; 6:120-129.

Strober B, Berger E, Cather J, Cohen D, Crowley JJ, Gordon KB, Gottlieb A, Horn EJ, Kavanaugh AF, Korman NJ, Krueger GG, Leonardi CL, Menter A, Schwartzman S, Sobell JM, Young M. A series of critically challenging case scenarios in moderate to severe psoriasis: a Delphi consensus approach. Journal of the American Academy of Dermatology 2009 Jul; 61(1 Suppl 1):S1-S46.

SYSTEMIC LUPUS ERYTHEMATOSUS/ ANTIPHOSPHOLIPID SYNDROME Aizer J, Karlson EW, Chibnik LB, Costenbader KH, Post D, Liang MH, Gall V, Gerhard-Herman MD. A controlled comparison of brachial artery flow mediated dilation (FMD) and digital pulse amplitude tonometry (PAT) in the assessment of endothelial function in systemic lupus erythematosus. Lupus 2009; 18(3):235-42.

Aringer M, Crow MK. A bridge between interferon-alpha and tumor necrosis factor in lupus. The Journal of Rheumatology 2008; 35:1473-6.

Bucciarelli S, Erkan D, Espinosa G, Cervera R. Catastrophic antiphospholipid syndrome: treatment, prognosis, and the risk of relapse. Clinical Reviews in Allergy and Immunology 2009 Jun; 36(2-3):80-4. Review.

26

Cantaert T, De Rijcke L, Mavragani CP, Wijbrandts CA, Niewold TB, Niers T, Vandooren B, Veys EM, Richel D, Tak PP, Crow MK, Baeten D. Exposure to nuclear antigens contributes to the induction of humoral autoimmunity during TNF alpha blockade. Annals of the Rheumatic Diseases 2008 Jul 14 [Epub ahead of print].

Cervera R, Bucciarelli S, Plasín MA, Gómez-Puerta JA, Plaza J, Pons-Estel G, Shoenfeld Y, Ingelmo M, Espinos G. Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group (European Forum on Antiphospholipid Antibodies). Catastrophic antiphospholipid syndrome (CAPS): descriptive analysis of a series of 280 patients from the “CAPS registry.” Journal of Autoimmunity 2009 May-Jun; 32(3-4):240-5. [Epub 2009 Mar 26].

Crow MK. Fast forward for systemic lupus erythematosus clinical trials. Nature Clinical Practice Rheumatology 2008; 4:387.

Crow MK, Kirou KA. Interferon-induced versus chemokine transcripts as lupus biomarkers. Arthritis Research & Therapy 2008; 10:126. [Epub 2008 Dec 18].

Cutolo M, Matucci-Cerinic M, Lockshin M, Ostensen M. Introduction: new trends in pregnancy and rheumatic diseases.

Rheumatology (Oxford) 2008 Jun; 47 Suppl 3:iii1.

DiMartino SJ, Yuan W, Redecha P, Ivashkiv L, Salmon JE. Insoluble immune complexes are highly effective triggers of IL-10 production in human monocytes and synergize with TLR ligands and C5a. Journal of Allergy and Clinical Immunology 2008; 127: 56-65.

Doria A, Tincani A, Lockshin M. Challenges of lupus pregnancies.

Rheumatology (Oxford). 2008 Jun; 47 Suppl 3:iii9-12.

Erkan D, Lockshin MD. New approaches for managing antiphospholipid syndrome. Nature Clinical Practice Rheumatology 2009 Mar; 5(3):160-70.

Erkan D, Patel S, Nuzzo M, Gerosa M, Meroni PL, Tincani A, Lockshin MD. Management of the controversial aspects of the antiphospholipid syndrome pregnancies: a guide for clinicians and researchers. Rheumatology (Oxford). 2008 Jun; 47 Suppl 3:iii23-7.

Fernandex DR, Telarico T, Bonilla E, Li Q, Banerjee S, Middleton FA, Phillips PE, Crow MK, Oess S, Muller-Esterl W, Perl A. Activation of mammalian target of rapamycin controls the loss of TCRzeta in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation. The Journal of Immunology 2009; 182:2063-73.

George D, Vasanth L, Erkan D, Bass A, Salmon J, Lockshin MD. Primary Antiphospholipid Syndrome Presenting as HELLP Syndrome: A Clinical Pathology Conference held by the Division

of Rheumatology at Hospital for Special Surgery. HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery.

2007 Sep; 3(2):216-21. [Epub 2007 Apr 26].

Gordon JK, Magro C, Lu T, Schneider R, Chiu A, Furman RR, Solomon G, Bass A, Erkan D. Overlap between systemic lupus erythematosus and Kikuchi Fujimoto disease: a clinical pathology conference held by the Division of Rheumatology at Hospital for Special Surgery. HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery 2009 Jul 16. [Epub ahead of print].

Kariuki SN, Crow MK, Niewold TB. The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high IFN-alpha activity and low tumor necrosis factoralpha levels in patients with lupus. Arthritis & Rheumatism 2008; 58:2818-23.

Kariuki SN, Kirou KA, MacDermott EJ, Barillas-Arias L, Crow MK, Niewold TB. Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo. The Journal of Immunology 2009 Jan 1; 182(1):34-8.

Kariuki SN, Moore KA, Kirou KA, Crow MK, Utset TO, Niewold TB. Age- and gender-specific modulation of serum osteopontin and interferon-áby osteopontin genotype in systemic lupus erythematosus. Genes & Immunity [advance online publication 2 April 2009].

Kim S, Moskowitz NK, Dicarlo EF, Bass AR, Erkan D, Lockshin MD. Catastrophic antiphospholipid syndrome triggered by sepsis.

HSS Journal: The Musculoskeletal Journal of Hospital for Special Surgery 2009 Feb; 5(1):67-72. [Epub 2008 Dec 19].

Lockshin MD. Update on antiphospholipid syndrome. Bulletin of the NYU Hospital for Joint Diseases 2008; 66(3):195-7. Review.

Lockshin MD, Derksen RH. New developments in lupus-associated antiphospholipid syndrome. Lupus 2008; 17(5):443-6. Review.

Lynch AM, Gibbs RS, Murphy JR, Byers T, Neville MC, Giclas PC, Salmon JE, Van Hecke TM, Holers MV. Complement activation fragment Bb in early pregnancy and preterm birth. American Journal of Obstetrics & Gynecology 2008; 199: 354.e1-8.

Lynch AM, Murphy JR, Byers T, Gibbs RS, Neville MC, Giclas PC, Salmon JE, Holers MV. Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia. American Journal of Obstetrics & Gynecology 2008; 198: 385.e1-9 [Epub 28 Jan 2008].

Niewold TB, Adler JE, Lehman TJA, Harley JB, Crow MK. Age- and sex-related patterns of serum interferon alpha activity in lupus families. Arthritis & Rheumatism 2008; 58:2113-9.

27

2008-2009 SELECTED PUBLICATIONS

SYSTEMIC LUPUS ERYTHEMATOSUS/ ANTIPHOSPHOLIPID SYNDROME (CONT.) Niewold TB, Kelly JA, Flesch MH, Espinoza LR, Harley JB, Crow MK. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients. Arthritis & Rheumatism 2008; 58:2481-7.

Onel KB, Huo D, Hastings D, Fryer-Biggs J, Crow MK, Onel K. Lack of association of the TP53 Arg72Pro SNP and the MDM2 SNP309 with systemic lupus erythematosus in Caucasian, African American, and Asian children and adults. Lupus 2009; 18:61-6.

Ostensen M, Lockshin M, Doria A, Valesini G, Meroni P, Gordon C, Brucato A, Tincani A. Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs. Rheumatology (Oxford). 2008 Jun; 47 Suppl 3:iii28-31.

Peerschke EI, Yin W, Alpert DR, Roubey RAS, Salmon JE, Ghebrehiwet B. Serum complement activation on heterologous platelets is associated with arterial thrombosis in patients with systemic lupus erythematosus and antiphospholipid antibodies.

Lupus 2009; 18: 530-38.

Salmon JE, de Groot P. Pathogenic role of antiphospholipid antibodies. Lupus 2008; 17:405-11.

VASCULITIS AND SCLERODERMA Chyou S, Ekland EH, Carpenter AC, Tzeng T, Tian S, Michaud M, Madri JA, and Lu TT. Fibroblast-type reticular stromal cells regulate the lymph node vasculature. Journal of Immunology 2008; 181: 3887-3896.

Finkelman J, Merkel P, Schroeder D, Hoffman G, Spiera R, St.Clair W, Davis J, Mccune J, Lears A, Ytterberg S, Hummel A, Viss M, Peikert T, Stone J, Specks U. Glycosylation of proteinase 3 (PR3) is not required for its reactivity with antineutrophil cytoplasmic antibodies (ANCA) in Wegener’s granulomatosis.

Clinical and Experimental Rheumatology. On Line: Internet submissionclinexprheumatol.org.

Mahr AD, Neogi T, LaValley MP, Davis JC, Hoffman GS, McCune WJ, Specks U, Spiera RF, St. Clair EW, Stone JH, Merkel PA. Assessment of the Item Selection and Weighting in the Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BV AS/WG). Arthritis Care and Research 2008 May; 59 (6): 884-891.

Postlethwaite AE, Wong WK, Clements P, Chatterjee S, Fessler BJ, Kang AH, Korn J, Mayes M, Merkel PA, Molitor J, Moreland L, Rothfield N, Simms RW, Smith EA, Spiera R, Steen V, Warrington K, White B, Wigley F, Furst. A multicenter, randomized,

28

double-blind, placebo-controlled trial of oral type I collagen treatment in patients with diffuse cutaneous systemic sclerosis: I. Oral type I collagen does not improve skin in all patients, but may improve skin in late-phase disease. Arthritis & Rheumatism 2008 May; 58 (6): 1810-1822.

Spiera RF, Gordon JK, Mehta M, Kirou KA, Lyman S, Kloiber SA, Crow MK. Phase IIa trial of Imatnib Mesylate (Gleevec®) in the treatment of diffuse systemic sclerosis: an interim analysis.

Arthritis & Rheumatism 2008 Oct;58 (9):1222, S623-4.

Wung PK, Anderson T, Fontaine KR, Hoffman GS, Specks U, Merkel PA, Spiera R, Davis JC, St.Clair EW, McCune WJ, Stone JH. Effects of glucocorticoids on weight change during the treatment of Wegener’s granulomatosis. Arthritis & Rheumatism 2008 May; 59 (5): 746-753.

BOOK CHAPTERS Ashany D, Crow MK. Experimental approaches to the study of autoimmune rheumatic diseases. In: Essential Clinical Immunology.

Edited by J B Zabriskie. Cambridge Medicine 2009; 175-97.

Erkan D. Lockshin MD. Antiphospholipid Syndrome. In: Clinical Immunology: Principles and Practice, 3rd Edition. Eds. Rich RR et al. Mosby Elsevier, Philadelphia 2008; p: 909-917.

Erkan D, Salmon J, Lockshin MD. Antiphospholipid Syndrome.

In: Kelley’s Textbook of Rheumatology, 8th Edition. Eds: Ruddy S, Harris ED, Jr., Sledge C. Elsevier Saunders, Philadelphia 2008; p:1301-1310.

Gordon J, Goldenberg D, Erkan D, Lockshin MD. Difficult Clinical Situations in Antiphospholipid Syndrome. In: Handbook of Systemic Autoimmune Diseases, Antiphospholipid Syndrome.

Ed: Asherson RA, Cervera R. Elsevier, Amsterdam 2009; p:215-234.

Lockshin MD, Salmon J, Erkan D. Pregnancy and Rheumatic Disease. In: Creasy and Resnik’s Maternal-Fetal Medicine, 6th Edition. Eds: Creasy RK, Resnik RR, Iams JD, Lockwood CJ, Moore TR. Elsevier, Philadelphia 2008; p1079-1088.

Sammaritano LR. Management of the patient with rheumatic disease during and after pregnancy. In: Targeted Treatment of Rheumatic Diseases. Michael H. Weisman, Michael E. Weinblatt, James S. Louie and Ronald F. van Vollenhoven. pp 436-455.

(In press) 2009, Elsevier (Saunders).

Zabriskie JB, Gibofsky A, Van Voorhis W, Buckner FS, Rose NR: Immunological aspects of cardiac disease. In: Essential Clinical Immunology. Edited by JB Zabriskie. Cambridge University Press. 2009.