Comparative Risks of Infection with Belimumab versus Oral Immunosuppressants in Patients with Non-Renal Systemic Lupus Erythematosus.

OBJECTIVE: We investigated the comparative risk of infection with belimumab versus oral immunosuppressants for the treatment of systemic lupus erythematosus (SLE).

METHODS: Using observational data from a U.S. multi-center electronic health record database, we identified patients with SLE but without lupus nephritis who initiated belimumab, azathioprine, methotrexate, or mycophenolate between 2011-2021. We designed and emulated hypothetical target trials to estimate the cumulative incidence and hazard ratios (HRs) of serious infection and hospitalization for serious infection comparing belimumab vs. each oral immunosuppressant. We used propensity score overlap weighting to balance baseline covariates and adjusted for adherence to treatment group using inverse probability of treatment weighting. We also assessed the control outcome of traumatic injury.

RESULTS: Among 21,481 patients, we compared 2841 and 6343 initiators of belimumab and azathioprine, 2642 and 8242 initiators of belimumab and methotrexate, and 2813 and 8407 initiators of belimumab and mycophenolate, respectively. After propensity score overlap weighting, all covariates were balanced in each comparison, with mean age 45 years and 94% females. Compared to azathioprine and mycophenolate, belimumab was associated with lower risks of both serious infection (HRs 0.82 [95% CI 0.72-0.92] and 0.69 [0.61-0.78]), and hospitalization for infection (HRs 0.73 [95% CI 0.57-0.94] and 0.56 [0.43-0.71]). The risk of infection was also lower for belimumab compared with methotrexate (HR 0.86 [95% CI 0.76-0.97]). There were no differences in traumatic injury risks across treatment groups.

CONCLUSION: Belimumab was associated with lower risks of serious infection than oral immunosuppressants. This finding should inform risk/benefit considerations for SLE treatment. This article is protected by copyright. All rights reserved.