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Frailty and risk of serious infections in patients with rheumatoid arthritis treated with biologic or targeted-synthetic DMARDs

Background: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic (b) or targeted synthetic disease modifying anti-rheumatic drugs (tsDMARDs).

Methods: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi bDMARDs, or Janus Kinase inhibitors (JAKi) between 2008-2019, 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 (aHRs) and 95% confidence intervals (95% CI) 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, 8111 (14%) non-TNFi biologics, and 1730 (3%) JAKi. Among these, 3560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (aHR (95% CI): 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions 1.4 (95% CI, 1.3-1.6) compared to non-frail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to non-frail patients among those on TNFi (1.2, 95% CI 1.1-1.3) or non-TNFi (1.2, 95% CI 1.0-1.4) or JAKi (95% CI 1.4, 1.0-2.0).

Conclusion: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with b- or tsDMARDs. 

 

Comments:

This study is pretty insightful—it shows a clear link between frailty and adverse outcomes in patients with rheumatoid arthritis (RA) who are starting biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs or tsDMARDs). Frailty, identified through a Claims-Based Frailty Index, seems to significantly increase the risk of serious infections and hospitalizations among these patients.

It's noteworthy that frail patients initiating TNFi (tumor necrosis factor inhibitors) had a higher risk of serious infections and inpatient admissions compared to non-frail patients. Frailty also increased the risk of any infection among patients on TNFi, non-TNFi biologics, or JAK inhibitors.

Understanding how frailty impacts treatment outcomes is crucial for managing RA more effectively. Identifying patients at higher risk due to frailty could lead to tailored interventions or closer monitoring to mitigate these risks.

Do you have any specific thoughts or questions about this study?

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