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Association of Seropositivity and Mortality in Rheumatoid Arthritis and the Impact of Treatment With Disease-Modifying Antirheumatic Drugs

Author

Alemao E1, Bao Y1, Weinblatt ME2, Shadick N2. Arthritis Care Res (Hoboken). 2019 Sep 17. doi: 10.1002/acr.24071. [Epub ahead of print]

Author Information

1 Bristol-Myers Squibb, Princeton, New Jersey, USA.

2 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Abstract

OBJECTIVE: 

Seropositivity for anti-citrullinated protein antibody (ACPA)/rheumatoid factor (RF) in rheumatoid arthritis (RA) is associated with increased overall mortality; however, association between antibody titers and mortality is not well-established. Investigating relationships between antibody titers and mortality may clarify their role in RA pathogenesis. This study evaluated association of antibody titers with mortality and its modification by disease-modifying antirheumatic drugs (DMARDs).

METHODS: 

Eligible patients with established RA were identified through administrative claims data linked to laboratory results (2005-2016). Patients were categorized by positive status for ACPA/RF, or both. Patients were further divided into groups by autoantibody titers. DMARD-exposed patients were categorized into biologic (b)DMARD and conventional (c)DMARD subcohorts. Crude mortality rates/1000 patient-years and Kaplan-Meier curves were compared between antibody categories. Adjusted Cox proportional hazard regression and sensitivity (propensity-matched patients) analyses were conducted.

RESULTS: 

Overall, 53,849 and 79,926 patients had evaluable ACPA and RF status, respectively. For both autoantibodies, mortality rates were significantly higher in seropositive versus seronegative patients (risk increase of 48.0% and 44.0% in ACPA- and RF-positive patients, respectively; p<0.001 each). Mortality rates were greatest in patients with higher versus lower autoantibody titers (ACPA, hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.45-1.76; RF, HR 1.78; 95% CI 1.66-1.91). In cDMARD-exposed patients, HRs were higher in seropositive versus seronegative cohorts; in bDMARD-exposed patients, there was no difference in mortality by serostatus.

CONCLUSION: 

Elevated ACPA/RF titers were independently associated with increased mortality among patients with RA, and persisted in patients treated with cDMARDs but not with bDMARDs.