ArticleTherapeutic advances in musculoskeletal disease2026
Serious infection risk in older adults with RA receiving biologic or targeted synthetic DMARDs: the role of age at disease onset.
Article in Therapeutic advances in musculoskeletal disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Older age is a risk factor for serious infection (SI) associated with biologic or targeted synthetic DMARDs (b/tsDMARDs) use in rheumatoid arthritis (RA). Among older adults with RA, one-third are diagnosed at ⩾60 years (late-onset RA, LORA), while others are diagnosed earlier (young-onset RA, YORA). LORA is characterized by a more acute onset and heightened inflammatory burden due to age-related immune dysregulation. Whether RA onset age independently affects infection risk with b/tsDMARDs remains unclear. Objective: Evaluate SI risk in older adults with RA initiating b/tsDMARDs, stratified by RA onset age: LORA versus YORA. Design: Retrospective cohort study using prospectively collected registry data. Methods: From FORWARD, the National Databank for Rheumatic Diseases (2001-2019), we identified RA patients aged ⩾60 years who initiated (1) anti-TNF then (2) subsequent non-TNF b/tsDMARDs. Patients were categorized as LORA versus YORA and matched using kernel-based propensity scores. SI was defined as an infection requiring hospitalization, intravenous antibiotics, or death. Multivariable Cox models estimated the risk of SI in LORA versus YORA. Results: Among 1379 LORA and 2727 weighted YORA patients initiating anti-TNF therapy, the crude incidence of SI was 28.2 and 20.5 per 1000 person-years. In adjusted models, LORA was not associated with increased anti-TNF-related SI risk compared to YORA (HR 0.82, 95% CI 0.63-1.02). Among 198 LORA and 675 weighted YORA patients subsequently initiating non-TNF b/tsDMARDs, the crude incidence of SI was 17.3 versus 19.5 per 1000 person-years. In adjusted models, LORA was not associated with increased non-TNF related SI risk (aHR 0.81, 95% CI 0.31-2.12). Across cohorts, older age was independently associated with increased SI risk. For anti-TNF, prior SI and recent long-term glucocorticoid use, and for non-TNF, HAQ disability were also associated with SI. Conclusion: Age at RA onset was not independently associated with SI risk following b/tsDMARD initiation. Risk stratification should prioritize functional status and treatment history.
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