Trimethoprim-sulfamethoxazole (TMP-SMX) was dispensed to only a minority of patients with granulomatosis with polyangiitis (GPA), a form of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), who are also being treated with rituximab.

The optimal use and duration of TMP-SMX is still unknown, according to a study published in Arthritis Research & Therapy.

Rituximab is often prescribed as a first-line therapy against GPA; however, approximately 25% of patients will still experience serious infections, which may lead to death. Low-dose TMP-SMX prophylaxis is typically prescribed to prevent Pneumocystis jirovecii pneumonia. Studies indicate that TMP-SMX can also reduce all-cause serious infections in patients with AAV. The authors of the study sought to characterize the frequency and persistence of TMP-SMX prophylaxis among patients with GPA treated with rituximab in a US population sample. 

The research team identified patients with GPA using the Merative Marketscan® Research Databases, which primarily contain data on employer-sponsored health insurance for those under 65 years of age and Medicare-eligible retirees with employer-sponsored Medicare supplemental plans for patients aged 65 years and above. The researchers narrowed their search to patients insured between January 1, 2011, and December 31, 2020. Patients must have at least 1 inpatient claim or 2 outpatient claims at least 30 days apart for GPA and be on rituximab. 

Read more about AAV etiology 

The primary outcome was TMP-SMX prophylaxis for a period of 28 days or more. The TMP-SMX must have been dispensed before rituximab but long enough to overlap with rituximab usage, or be dispensed within 30 days following the rituximab prescription. 

The researchers identified 1877 patients who were diagnosed with GPA and receiving rituximab. A total of 426 (23%) patients were administered TMP-SMX prophylaxis, while the rest (73%) were not. Univariable analysis revealed that a TMP-SMX prescription was significantly associated with prednisolone usage of 20 mg or more per day or 1 to 19 mg/day in the month prior to rituximab. 

“Further work is needed to determine the association of TMP-SMX use with infectious outcomes in this population in order to strengthen the evidence on optimal use of TMP-SMX during rituximab treatment in AAV,” the authors concluded. 


Mendel A, Behlouli H, de Moura CS, Vinet É, Curtis JR, Bernatsky S. Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort studyArthritis Res Ther. Published online July 29, 2023. doi:10.1186/s13075-023-03114-7