Risk of Serious Infection in Patients With Rheumatoid Arthritis Treated With Biologic Versus Nonbiologic Disease-Modifying Antirheumatic Drugs.

Objective: The objective of this study is to examine the risk of serious infections (SIs) associated with biological disease-modifying antirheumatic drugs (bDMARDs) compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA).

Methods: We studied patients with RA who initiated bDMARDs or csDMARDs from 2001 to 2016 in FORWARD-The National Databank for Rheumatic Diseases. Disease-modifying antirheumatic drugs (DMARDs) were categorized into three groups: (1) csDMARDs (bDMARD-naïve; reference), (2) tumor necrosis factor α inhibitors (TNFis), and (3) non-TNFi biologics (abatacept, rituximab, tocilizumab, and anakinra). SIs were defined as those requiring intravenous antibiotics or hospitalization or those resulting in death. We calculated the propensity score (PS), which reflected the probability of receiving a specific DMARD group, and estimated the hazard ratio (HR) (with the 95% confidence interval [CI]) for SI from multivariable Cox models, adjusting for PS and time-varying confounders.

Results: A total of 694 (5.9%) first SIs were identified in 11 623 patients with RA during 27 552 patient-years of follow-up. The SI incidence rate per 1000 patient-years was 22.4 (95% CI 19.2-26.1) for csDMARDs, 26.9 (95% CI 24.5-29.6) for TNFis, and 23.3 (95% CI 19.0-28.5) for non-TNFi bDMARDs. Adjusted HRs for SIs were 1.33 (95% CI 1.05-1.68) for TNFis and 1.48 (95% CI 1.02-2.16) for non-TNFi bDMARDs, compared with csDMARDs. The SI risk with non-TNFi bDMARDs versus TNFis was not different. Other risk factors for SI were older age, higher comorbidity burden (particularly pulmonary disease), higher weighted cumulative prednisone dose, disability and disease activity, and number of prior csDMARD failures.

Conclusion: TNFis and non-TNFi bDMARDs were associated with an increased SI risk compared with csDMARDs in RA, even after accounting for risk-associated patient characteristics.