Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted-Synthetic Disease-Modifying Antirheumatic Drugs

Abstract

Objective: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs.

Methods: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class.

Results: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0]).

Conclusion: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs.

Figure 1.

Figure showing the cohort selection

Figure2.

Cox proportional hazard curves showing risk of serious infections among frail versus non-frail patients stratified by drug class

Figure 3.

Cox proportional hazard curves showing risk of any infection among frail versus non-frail patients stratified by drug class.

Figure 4.

Cox proportional hazard curves showing risk of all-cause admissions among frail versus non-frail patients stratified by drug class.