Background/Purpose: Recently, it has been recognized that frailty and pre-frailty are common in patients with rheumatoid arthritis (RA) [1]. Whether frailty status portends an increased risk of adverse outcomes in patients with RA on biologic or targeted synthetic disease modifying anti-rheumatic drugs (b- or tsDMARDs) remains unknown. Our objective was to evaluate the association between frailty and risk of infections in patients with RA exposed to b- or tsDMARDs.

Methods: Using the IBM/Watson MarketScan® Commercial Claims and Encounters Databases, we identified all patients with RA who filled new prescriptions (or received infusions) for TNFα antagonists (TNFi), non-TNFi biologics (rituximab, abatacept, tocilizumab) or Janus Kinase inhibitors (JAKi) between 2008-2019. The date of the first prescription within these three drug categories was the index date. Patients’ frailty risk score was calculated using the Claims-Based Frailty Index (CFI) [2, 3], which estimates a deficit-accumulation frailty index using International Classification of Diseases codes, Current Procedural Terminology codes, and Healthcare Common Procedure Coding System codes in administrative claims data in the 1-year baseline period. The index ranges from 0 (not at all frail) to 1 (severely frail). The primary outcome was time to infections requiring hospitalization. Secondary outcomes included outpatient or inpatient encounters for infections and all-cause hospitalizations.

Patients were followed until 1) outcome occurrence; 2) disenrollment; 3) >90 days elapsed (or >180 days for rituximab) without further fills of the first drug categories; 4) they filled/received infusions of b/tsDMARDs from a different drug category; or 5) 2 years after index. We used Cox proportional hazards adjusting for demographics, calendar year, serious and/or opportunistic infections in the 12-months prior to index to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (95% CIs) for each outcome. In separate model, we additionally adjusted for comorbidity burden, and health care utilization (HCU).

Results: A total of 62,246 patients with RA met our inclusion criteria of whom 50,910 (82%) started TNFi as their first biologic, 9525 (15%) non-TNFi biologics, and 1811 (3%) JAKi. Among these, 3928 (6%) were considered frail (Table 1). In multivariable analyses, frail patients had higher risk of serious infections compared to non-frail patients (aHR 2.37, 95% CI 2.05-2.74) which decreased to aHR 1.34, 95% CI 1.13-1.58 (Table 2, Figure 1) after adjusting for comorbidity burden and the HCU. Similarly, frailty was associated with increased risk of any infection (aHR 1.18, 95% CI 1.11-1.25), and all-cause hospitalizations (aHR 1.34, 95% CI 1.21-1.49) relative to non-frail individuals.

Conclusion: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with b- or tsDMARDs. Our findings underscore the need for considering this parameter in patient evaluations (even among younger patients) in the clinic.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/frailty-is-associated-with-serious-infections-in-biologic-and-targeted-synthetic-dmard-treated-patients-with-rheumatoid-arthritis/