Advances in Inflammatory Arthritis Clifton O. Bingham III, MD Associate Director, Johns Hopkins Arthritis Center

1. Advances in Inflammatory Arthritis Clifton O. Bingham III, MD Associate Director, Johns Hopkins Arthritis Center Divisions of Rheumatology and Allergy and Clinical Immunology Johns Hopkins University Baltimore, Maryland, USA

2. Progress in Rheumatoid Arthritis • Early Disease Recognition • Anti-CCP Antibodies (Anti-citrullinated peptide antibodies, ACPA)1 • Disease-specific serum markers for disease • Associated with worse prognosis • May appear earlier than other markers (e.g. rheumatoid factor) • American College of Rheumatology/European League against Rheumatism (ACR-EULAR) Definitions for RA and Early inflammatory arthritis • Increasing primary care provider awareness, education • Association of disease and damage with cigarette smoking2 • Disease-related comorbidities • Cardiovascular disease, malignancy, infection, fatigue, anemia • Goals of Therapy • Decrease signs and symptoms • Improve physical function • Prevent damage • Limit disability

3. Progress in RA Treatment • Disease-modifying anti rheumatic drugs (DMARDS) • Preventing damage and progression • No longer “start low, go slow” • ACR and EULAR Guidelines for RA Treatment1,2 • More aggressive treatment regimens • Methotrexate as cornerstone of therapy, alone and combinations • Target of Therapy: Low Disease Activity State or “Remission” • BeST3, TICORA4, others • ACR/EULAR/OMERACT Definitions of Low Disease Activity/Remission5,6 • Approval of Biological DMARDS for RA • First agent approved 1999, currently 8 approved US, 9 approved EU • Inhibitors of TNF, IL-1, IL-6, T-Cell Costimulation, B Cells • Evaluating Strategies of Treatment • Treatment paradigms: BeST3, TEAR, induction, step up, step down • ACR/EULAR/OMERACT Clinical Trial Outcomes7

4. Progress in RA Outcomes • Lower SES associated with worse outcomes1,2 • Improvement in physical function and HR-QoL3 • Improvement in work productivity • Attenuation of absenteeism, increase presenteeism4 • Improvement in some comorbidities with treatment • Anemia5 • Cardiovascular6 • Increased infections • Bacterial and atypical/opportunistic (e.g. MTb, fungal, zoster) • Highlights need for more surveillance, screening, immunization

5. Recent Progress in Spondyloarthritis • Disease recognition • Development and revision of Diagnostic and Classification Criteria for Psoriatic Arthritis1 and Ankylosing Spondylitis2 • Active international consortia to study these diseases (e.g. GRAPPA, ASAS, CASPAR) • Disease-related comorbidities recognized: cardiovascular disease3 • Approvals of several drugs for Psoriatic Arthritis • Approvals of several drugs for Ankylosing Spondylitis • Data-driven, Consensus-based Treatment Recommendations3,4 • Improvement in Physical Function and QoL5 • Disease modification demonstrated in PsAand under study in AS

6. Recent Progress in Juvenile Arthritis • Research consortia and clinical networks (e.g. PRINTO, CARRA) to concentrate care and facilitate investigation • Approvals for drugs in JIA • Established Regulatory Pathway • Ethical Clinical Trial Designs (Withdrawal/Flare) • Improved clinical outcomes • Concerns re: longer term safety surveillance for adverse effects (malignancy, lymphoma, leukemia1, and infection) • Cryopyrin-Associated Periodic Syndromes2 • NOMID, Muckle-Wells, Familial Cold Autoinflammatory Syndrome • IL-1 inhibitors approved for treatment (including orphan drug indication) • Critical shortage of Pediatric Rheumatologists3 • Lobbying efforts for Arthritis Prevention and Cure Act US Congress

7. Recent Progress in Gout • Revised Diagnostic and Treatment Guidelines1,2 • Identification of genetic loci for hyperuricemia3 • Recognition of effects of chronic gout: • Reduction in HR-QoL • Increase in health care utilization4 • Better understanding of gout-related comorbidities • Metabolic syndrome5 • Cardiovascular disease6 • Approval of new drug for gout; additional agents under investigation

8. Potential Impact of Health Care Systems on Outcomes • Access to medical care • Access to specialist evaluation • Access to medications • Differing requirements for prescribing/continuation • Country-to-country variability • Insurer-to-insurer variability • Access to clinical trials • Health literacy • Local infection concerns (e.g. MTb) • Cost

9. Ongoing Research Agenda • Real World Risk/Benefit and Cost/Efficacy Analysis • Methods to Assess Effectiveness • Additional outcomes: employment, disability, joint failure, participation, comorbidities (e.g. CVD) • Patient-reported outcomes (e.g. PROMIS, WHO/ICF) • Common Data Capture for Registries for Safety and Efficacy • NDBRD, CORRONA, BSBR, RABBIT, BIOBADASER, QUEST-RA, TETRAD, etc, • Enhanced Post-marketing Surveillance to Capture Rare Adverse Events • patient-years of exposure vs. patient-years) • Ethical Considerations in Clinical Trials1 • Whom to study in an era of effective therapy • Maintenance of clinical equipoise • Developing Outcome Measures for Novel Study Designs • Induction/withdrawal, tapering (e.g. “flare”)2 • Treatment Strategy and Head-to-head Comparison studies • “Biosimilars” and Small molecules • Screening and prevention of risk (e.g. TB screening, immunization)