Rheumatoid Arthritis: An update for non rheumatologists Dimitrios Pappas, M.D., M.P.H. Assistant Professor of Medicine Columbia University, College of Physicians & Surgeons Director of Rheumatology Athens Medical Center Scientific Director, Consortium of Rheumatology Researchers Of North America Cell:6948230543 Email:dp2544@columbia.edu www.dpappas.gr GDS_80000_Title_v1 1
Disclosures Grant funding in past 5 years from: NIH/NIAMS, American College of Rheumatology Research and Education Foundation, Arthritis Foundation Consultant: Novartis, RNS, CORRONA and CORRONA foundation GDS_80000_Title_v1 2
Outline RA basics: refresher RA comorbidities focus on CVD CVD Rates and Outcomes in RA Pharmacotherapies and Cardiovascular Risk CVD Risk evaluation in RA GDS_80000_Title_v1 3
RA Review: Features Auto-immune Disorder Prevalence 1% worldwide Peak Incidence 4 th to 6 th decade Female:Male 3:1 Characterized by: Synovitis of Diathrodial (Synovium Containing) Joints Synovial Hyperplasia Inflammatory Infiltration Erosive Damage to Adjacent Bone/Cartilage Joint Destruction/Deformity Systemic Inflammation Extra-Articular Features Increased Morbidity/Mortality GDS_80000_Title_v1 4
GDS_80000_Title_v1 5 RA Review: Joint Swelling
GDS_80000_Title_v1 6 RA Review: Erosions
GDS_80000_Title_v1 7 RA Review: Advanced Deformity
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RA: Guiding Principles of Treatment Treat early Treat hard Treat with a targeted goal Aim for an acceptable benefit to risk ratio Do not forget the comorbidities 9
It s not just the joints CVD 10 Years Earlier Osteoporosis 2x Rate Malignancy Joint Destruction Disability Pain 6-9x Serious Infection Rate Pulmonary Disease CVD=cardiovascular disease. Deane K. J Musculoskel Med. 2006;23:S24-S31. GI Bleeding 10
Survival Probability Increased Mortality in Patients with RA Kaplan-Meier Survival Curves in a U.S. Population U.S. Females 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 5 10 15 20 25 Years After Entry into Study U.S. Males Stanford RA Females Stanford RA Males Standardized Mortality Ratio = 3.08 for RA pts N=886 RA patients. Wolfe F, et al. Arthritis Rheum. 1994;37:481-494. 11
No Temporal Decline in RA Mortality Women Women Men Men From Gonzalez A et al. Arthritis Rheum 2007;56(11):3583-7. From Gonzalez A et al. Arthritis Rheum 2007;56(11):3583-7.
Event Rate per 1000 person-years Risk of MI, Stroke and CV-related Death are all Increased for Persons with Rheumatoid Arthritis 20 Persons with RA Persons without RA RR 1.6 (1.5 1.7) 15 10 RR 1.8 (1.7-2.0) RR 1.9 (1.7-2.1) RR 1.3 (1.2 1.4) 5 0 MI Stroke CV Death Any CV Event* * Myocardial infarction (MI), stroke, or cardiovascular (CV) death defined by ICD-9 codes in B.C. population 13 Solomon DH, et al. Ann Rheum Dis. 2006;65:1608-1612.
CVD Mortality in RA Mortality from CVD events increased 50% relative to non-ra control populations Across 24 cohort studies 111,758 patients 22,927 CV events Women = Men for CVD events leading to death From Avina-Zubieta et al. Arthritis Rheum 2008; 59(12): 1690-1697. From Avina-Zubieta et al. Arthritis Rheum 2008; 59(12): 1690-1697. GDS_80000_Title_v1 14
CVD Events Increased in RA and May Precede RA Diagnosis Population based cohort study, Rochester MN 603 RA patients; 1955-1995 In the 2 year period prior to RA diagnosis: Hospitalization for AMI 3-fold higher in RA Silent MI > 5-fold higher in RA RA patients half as likely to report angina After RA diagnosis: RA patients 64% less likely to receive coronary bypass Silent MI and Sudden Cardiac Death 2-fold higher in RA Maradit-Kremers, et al. Arthritis Rheum. 2005 GDS_80000_Title_v1 15
Carotid Plaque: Largest Relative Difference in Youngest Age Group From Kobayashi et al. J Rheumatol 2010; 37(4):730-9. GDS_80000_Title_v1 16
Heart Failure in RA is Characterized by a Different Phenotype than in Controls Fewer symptoms Higher Ejection Fraction From Davis JM 3rd et al. Arthritis Rheum 2008;58(9):2603-11. GDS_80000_Title_v1 17
Echocardiographic Diastolic Dysfunction Increased in RA From Liang et al. Ann Rheum Dis 2010. 69(9):1665-70. GDS_80000_Title_v1 18
Cardiac MRI: Left Ventricular Mass was Lower in RA vs. Controls at All Ages Men Women Red line RA Blue line Control Dotted line 95% confidence limit for the estimate of the mean Giles JT et al. Arthritis Rheum 2010; 62 (4): 940 951. GDS_80000_Title_v1 19
Mechanisms of CVD Risk in RA: Interaction of Traditional CVD Risk Factors and Inflammation GDS_80000_Title_v1 20
RA and CVD: Traditional Risk Factors May Have More Impact in Setting of Inflammation del Rincon I, et al. Arthritis Rheum. 2005:52:3413. GDS_80000_Title_v1 21
RA Severity is a Determinant of Subclinical Coronary Atherosclerosis From Giles et al. Arthritis Res Therapy 2009; 11(2):R36. GDS_80000_Title_v1 22
RA Severity is a Determinant of Subclinical Coronary Atherosclerosis From Giles et al. Arthritis Res Therapy 2009; 11(2):R36. GDS_80000_Title_v1 23
RA Severity is a Determinant of Subclinical Coronary Atherosclerosis From Giles et al. Arthritis Res Therapy 2009; 11(2):R36. GDS_80000_Title_v1 24
DMARDs and CVD in RA: Friends and Foes GDS_80000_Title_v1 25
DMARDs and CVD in RA MTX (vs. no MTX) treatment associated with lower overall mortality (hazard ratio 0.4) 1 And CV-related mortality (HR 0.3) Anti-TNF (vs. no anti-tnf) therapy associated with: Lower prevalence of CHF (3.1 vs. 3.8%) 2 Lower incidence rate of first CV events (14.0/1000 vs. 35.4/1000 personyrs) 3 Both associations remain statistically significant after adjustment for conventional CV risk factors 1 Choi HK, et al. Lancet. 2002;359:1173 2 Wolfe F, et al. Am J Med. 2004;116:305 3 Jacobsson LTH, et al. J Rheum. 2005;32:1213. GDS_80000_Title_v1 26
CVD Reduction with TNF inhibitors in RA Dependent on Response From Dixon WG et al. Arthritis Rheum 2007;56(9):2905-12. GDS_80000_Title_v1 27
Recommendations: Reducing the Impact of CVD in RA Patients GDS_80000_Title_v1 28
Intervention and Prevention: Now and Tomorrow Now There are no studies evaluating intervention and prevention specifically for RA patients Current guidelines (quasi evidence based) recommend aggressive management of traditional risk factors and RA disease activity Model: CVD prevention and treatment in diabetes Lingering questions How aggressive? Evaluation---does it work? GDS_80000_Title_v1 29
From Peters et al. Ann Rheum Dis 2010;69(2):325-31. GDS_80000_Title_v1 30
From Peters et al. Ann Rheum Dis 2010;69(2):325-31. GDS_80000_Title_v1 31
Evaluation: Are RA Patients Meeting CVD Risk Reduction Targets? GDS_80000_Title_v1 32
Targets for Secondary Prevention After MI not met in RA Patients Danish National Patient Register 66,107 MI patients (877 with RA) RA patients less likely to be started on aspirin, beta blockers, and statins Long term adherence to ACE inhibitors and ARBs lower From Lindhardsen et al. Ann Rheum Dis 2012; 71(9): 1496. GDS_80000_Title_v1 33
GDS_80000_Title_v1 34 Thank you!