Glucocorticoid Adjustment Attenuates Infection Risk Differences Among Nonrenal Lupus Therapies

A target trial emulation published in Arthritis & Rheumatology compared infection-related hospitalization among 6,168 patients with nonrenal systemic lupus erythematosus initiating azathioprine, belimumab, methotrexate, or mycophenolic acid analogues (MPAAs). Investigators used Optum Labs claims from March 2011 through September 2023, excluding patients with prior lupus nephritis, transplantation, or rituximab/cyclophosphamide exposure. The primary outcome was time to first infection-related hospitalization.

At 24 months, cumulative hospitalization incidence was 10% with azathioprine, 8% with belimumab, 10% with methotrexate, and 13% with MPAAs. In intention-to-treat analyses, MPAAs were associated with higher risk than belimumab (hazard ratio [HR] 1.55, 95% CI 1.07–2.25) and methotrexate (HR 1.32, 95% CI 1.04–1.68). Per-protocol analyses found higher risk with azathioprine (HR 2.04, 95% CI 1.01–4.16) and MPAAs (HR 2.27, 95% CI 1.11–4.62) versus belimumab.

Between-treatment differences were no longer statistically significant after models incorporated monthly glucocorticoid dose during follow-up. These findings emphasize glucocorticoid exposure when interpreting serious infection risk, rather than establishing a definitive safety ranking. Postbaseline glucocorticoid use may reflect evolving disease activity and also mediate treatment effects on infection risk. The observational claims-based design limits causal interpretation; this report is based on the abstract, with full text unavailable.