A Clinical Context Report

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Rheumatoid Arthritis in Practice An Expert Commentary with Diane Horowitz, MD A Clinical Context Report

Rheumatoid Arthritis in Practice Jointly Sponsored by: and

Rheumatoid Arthritis in Practice Expert Commentary Supported in part by educational grants from Abbott and Centocor Ortho Biotech.

Rheumatoid Arthritis in Practice Clinical Context Series The goal of this series is to provide up-todate information and multiple perspectives on the pathogenesis, symptoms, risk factors, and complications of rheumatoid arthritis as well as current and emerging treatments and best practices in the management of rheumatoid arthritis.

Rheumatoid Arthritis in Practice Clinical Context Series Target Audience Rheumatologists, pain management specialists, geriatricians, family practice/ primary care physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals involved in the management of patients with rheumatoid arthritis.

Activity Learning Objective Upon successful completion of this educational program, participants should be able to: Review the relevance and significance of the activity in the broader context of clinical care.

CME Information: Physicians Statement of Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Perelman School of Medicine at the University of Pennsylvania and MedPage Today. The Perelman School of Medicine at the University of Pennsylvania is accredited by the ACCME to provide continuing medical education for physicians.

CME Information Credit Designation The Perelman School of Medicine at the University of Pennsylvania designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

CME Information: Physicians Credit for Family Physicians MedPage Today "News-Based CME" has been reviewed and is acceptable for up to 2098 Elective credits by the American Academy of Family Physicians. AAFP accreditation begins January 1, 2012. Term of approval is for one year from this date. Each article is approved for 0.5 Elective credits. Credit may be claimed for one year from the date of each article.

CE Information: Nurses Statement of Accreditation Projects In Knowledge, Inc. (PIK) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center s Commission on Accreditation. Projects In Knowledge is also an approved provider by the California Board of Registered Nursing, Provider Number CEP-15227. This activity is approved for 0.50 nursing contact hours. DISCLAIMER: Accreditation refers to educational content only and does not imply ANCC, CBRN, or PIK endorsement of any commercial product or service.

CE Information: Pharmacists Projects In Knowledge is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This program has been planned and implemented in accordance with the ACPE Criteria for Quality and Interpretive Guidelines. This activity is worth up to 0.5 contact hours (0.05 CEUs). The ACPE Universal Activity Number assigned to this knowledge-type activity is 0052-9999-12-839-H04-P.

Discussant Diane Horowitz, MD Attending Physician North Shore University Hospital Manhasset, NY Department of Medicine Division of Rheumatology LIJ Medical Center North Shore-LIJ Health System Assistant Professor Hofstra North Shore-LIJ School of Medicine

Disclosure Information Diane Horowitz, MD has disclosed that she has no relevant financial relationships or conflicts of interest to report.

Disclosure Information Dori F. Zaleznik, MD, Associate Clinical Professor of Medicine, Harvard Medical School, Boston; Nancy Walsh; and Dorothy Caputo, MA, BSN, RN, Nurse Planner; have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staff of The University of Pennsylvania School of Medicine Office of CME, MedPage Today, and Projects In Knowledge have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

Diagnosing Rheumatoid Arthritis: The Essentials Talk to the patient Take a careful history Do a thorough physical examination

Supporting the Diagnosis Imaging with x-rays, ultrasound, MRI Laboratory tests Rheumatoid factor Anti-CCP Kidney and hepatic function

Assess for Severity Erosive disease Symptoms Duration of disease

American College of Rheumatology 2012 Guidelines Revised guidelines emphasize: Treat early for better outcome, to prevent joint damage, and preserve function and quality of lfe Screen for tuberculosis Vaccinate as appropriate The goal is remission or low disease activity Source: Arthritis Care Res 2012; 64: 625-639

Initiating Treatment Mild disease: Consider nonsteroidal antiinflammatory drugs Moderate disease: Consider a disease-modifying anti-rheumatic drug (DMARD) such as methotrexate More severe disease: Consider adding another DMARD such as hydroxychloroquine or sulfasalazine, or starting a biologic agent

TNF Inhibitors Etanercept (Enbrel), weekly subcutaneous injection Infliximab (Remicade), intravenous infusions every 4 to 8 weeks Adalimumab (Humira), subcutaneous injection every other week Certolizumab pegol (Cimzia), subcutaneous injection every other week Golimumab (Simponi), subcutaneous injection once a month

Oral Therapies JAK inhibitors Tofacitinib Syk inhibitors Fostamatinib

Tofacitinib: Phase IIb Tral ACR20 responses: 5 mg twice daily, 59.2% (P<0.0001 versus placebo) 10 mg twice daily, 70.5% (P<0.0001) 15 mg twice daily, 71.9% (P<0.0001) Source: Arthritis Rheum 2012; 64: 617-629.

Fostamatinib: Phase II Study ACR20 responses: Placebo, 35% 100 mg twice daily, 67% (P<0.001) 150 mg once daily, 57% (P<0.001) Source: N Engl J Med 2010; 363: 1303-1312.

Targeting B Cells-1 Rituximab (Rituxan) Approved for use in RA for patients with inadequate response to TNF inhibitors

Targeting B Cells-2 Ocrelizumab efficacy: phase III studies: Efficacy endpoints met Higher rates of serious infections compared with placebo No further development for RA Source: Arthritis Rheum 2012; 64: 350-359. Arthritis Rheum 2012; 64: 360-370.

Pathogenesis of RA Genetics Shared epitope Candidate genes and SNPs Environment Gut flora Periodontal disease Smoking

A Revolution in Treatment Outlook is bright Disability is less New treatments are coming The goal is remission

Summary The diagnosis of RA is based on a careful history and physical examination, with imaging and laboratory tests as needed Initial treatment is based on disease severity The American College of Rheumatology has issued new treatment guidelines that emphasize early treatment, prevention of joint damage, and preservation of function and quality of life For disease that is moderate in severity, consider one or more disease-modifying drugs such as methotrexate For severe disease, consider using a TNF inhibitor or other biologic

Summary (cont d) There are currently four TNF inhibitors given subcutaneously and one given by infusion Oral therapies such as JAK and Syk inhibitors are under development Targeting B cells with rituximab is another second-line therapeutic option Current thinking on the pathogenesis of RA holds that the disease arises from a combination of genetics and environmental factors The goal of treatment today is remission and the outlook is bright