Less Than One-Third of US Patients With GPA Treated With Rituximab Receive TMP-SMX Prophylaxis

Women with GPA treated with RTX were less likely to receive TMP-SMX prophylaxis.

Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis was prescribed to only a small proportion of patients with granulomatosis with polyangiitis (GPA) receiving treatment with rituximab (RTX), particularly among those also receiving glucocorticoids who were recently hospitalized, according to study results published in Arthritis & Research Therapy.

Rituximab plays a crucial role in treating severe GPA, which is the predominant form of antineutrophilic cytoplasmic antibody-associated vasculitis (AAV) in North America.

Investigators conducted a retrospective cohort study and reported on the frequency, duration, and factors related to the use of TMP-SMX prophylaxis among patients with GPA who received treatment with RTX.

Insured adult patients with GPA were included in the study. Patients had at least 1 inpatient claim or 2 outpatient claims (minimum 30 days in between claims) with subsequent diagnostic codes for GPA and at least 1 code for RTX following initial GPA diagnosis.

The primary study outcome was baseline TMP-SMX prophylaxis, defined as prescriptions for TMP-SMX treatment lasting at least 28 days, given within 1 month of RTX initiation.

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 RTX treatment in AAV.

A total of 1877 patients with GPA treated with RTX were included in the analysis. Twenty-three percent (n=426/1877) of patients were prescribed baseline TMP-SMX for a median duration of 141 days.

According to multivariable analyses, TMP-SMX prophylaxis was associated with prednisone use in the month prior to RTX initiation (≥20 mg/day vs 0 mg/day: odds ratio [OR], 3.96; 95% CI, 3.0-5.2; 1-19 mg/day vs 0 mg/day: OR, 2.63; 95% CI, 1.8-3.8).

Female sex showed a negative association with TMP-SMX use (OR, 0.63; 95% CI, 0.5-0.8).

In the 6 months prior to RTX initiation, methotrexate use (OR, 1.48; 95% CI, 1.04-2.1), intensive care hospitalization (OR, 1.95; 95% CI, 1.4-2.7), and nonintensive care hospitalization (OR, 1.56; 95% CI, 1.2-2.1) were associated with use of TMP-SMX prophylaxis.

Of the 919 patients with 6 months of continuous insurance enrollment before RTX initiation, 281 (31%) received TMP-SMX at baseline.

By expanding the usage of TMP-SMX prescriptions to include those lasting at least 28 days given within 6 months after RTX initiation, researchers identified a total of 609 patients (183 new patients in addition to those included in the primary analysis) receiving TMP-SMX prophylaxis.

Multivariable analyses conducted on the complete cohort (N=1877; 32% receiving TMP-SMX) and the subgroup with 6 months of continuous insurance enrollment following RTX initiation (n=1308; 38% receiving TMP-SMX), yielded similar results to the primary analysis.

This study was limited by lack of data on medications administered in-hospital, potentially excluding certain patients from the cohort and leading to inadequate identification of prednisone exposure among hospitalized patients.

The study authors concluded, “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 RTX treatment in AAV.”

Disclosure: This research was partially supported by Fonds de Recherche Santé du Qué bec. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Mendel A, Behlouli H, de Moura CS, et al. Trimethoprim-sulfamethoxazole prophylaxis during treatment of granulomatosis with polyangiitis with rituximab in the United States of America: a retrospective cohort study. Arthritis Res Ther. Published online July 29, 2023. doi:10.1186/s13075-023-03114-7