Risk factors for adverse drug reactions to sulfamethoxazole-trimethoprim prophylaxis in patients with rheumatic and musculoskeletal diseases

Objectives: Risk factors for adverse drug reactions (ADRs) associated with prophylactic sulfamethoxazole-trimethoprim (SMX/TMP) in patients with rheumatic and musculoskeletal diseases undergoing immunosuppressive therapy remain unclear; we aimed to identify the risk factors associated with ADRs. Methods: Consecutive patients with rheumatic and musculoskeletal diseases, who were admitted to Keio University Hospital and received prophylactic administration of SMX/TMP, were included. Data regarding ADRs to SMX/TMP were collected to identify the associated risk factors using multivariable analysis. Results: Of 438 patients included in the analysis, 82 (18.7%) experienced ADRs. Patients in the ADR group were significantly older, had chronic kidney disease, and exhibited lower lymphocyte and platelet counts, lower albumin levels, lower estimated glomerular filtration rates, higher aspartate aminotransferase levels, and higher ferritin levels than those in the non-ADR group. Regarding the underlying rheumatic and musculoskeletal diseases, adult-onset Still's disease (ASD) was associated with a significantly higher incidence of ADRs (67%) than other diseases. Multivariable analysis identified the presence of ASD and low lymphocyte counts as independent risk factors for allergic ADRs and older age and use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers for nonallergic ADRs. Conclusions: Risk factors for ADRs associated with prophylactic SMX/TMP treatment in patients with rheumatic and musculoskeletal diseases were identified.