Background/Purpose: Serious infection events (SIE) and myocardial infarction (MI) are among the most concerning adverse events that occur in rheumatoid arthritis (RA) patients. The role of RA disease activity and associated systematic inflammation has been examined only in a limited fashion as it relates to these outcomes.

Methods: Multi-biomarker disease activity (MBDA) test scores (n=77,641) were linked to Medicare claims at a patient-level for individuals with RA who had at least 12 months of Medicare coverage from 2011-2014, excluding patients with other autoimmune diseases. The 4 outcomes studied were pneumonia or sepsis as the primary reason for hospitalization (SIE-primary); any pneumonia or sepsis during hospitalization (SIE-secondary); MI; and a composite CHD outcome (MI, PCI or CABG), using previously-validated definitions defined by ICD9 and HCPCS codes. Patients were excluded from the MI/CHD analysis for prior MI. The MBDA score was analyzed in a time-varying fashion, updated with each new test result, and analyzed according to its established disease activity cutpoints and in quartiles. MBDA scores were lagged by 1 week (MI/CHD) or 2 weeks (SIE). Tests were excluded (n=10,996) for vaccination, antibiotic use, or hospitalization within the prior 21 days. Patient baseline characteristics were measured at the time of the first usable MBDA test and in the previous 12 months. Cox proportional hazards models evaluated the association between MBDA score and SIE, MI, and CHD events, controlling for age, sex, and race.

Results: A total of 17,333 patients were eligible for the SIE, and 16,796 for the MI/CHD analyses. Baseline characteristics were mean (SD) age 69 (10) years, 79% women, 80% white, and 37% disabled. RA therapies included biologics (20%), MTX (55%), other non-biologic DMARDs (40%), and oral glucocorticoids (51%).  In up to 16,424 person-years of follow-up, there were 452 SIE-primary, 653 SIE-secondary, 132 MI, and 181 CHD events. The crude rates of all outcomes were associated with increasing MBDA score in a dose-response fashion (Table), using either established cutpoints or quartiles. After adjustment for age, sex, and race, higher MBDA score was associated with all outcomes of interest. Sensitivity analyses that examined the MBDA score without CRP, and separately adjusted for CRP, yielded similar findings to the main results.

Conclusion: Higher MBDA scores were associated with increased risk for hospitalized infection, MI, and CHD events in a large U.S. RA population predominantly consisting of older individuals. Use of the MBDA score to risk-stratify patients for these serious adverse events may help clinicians identify those at highest risk.