The role of Trimethoprim/sulfametoxazole in reducing relapses and risk of infec-tions in ANCA-associated vasculitis: a meta-analysis

OBJECTIVE: To assess available evidence from randomized controlled studies (RCT) and observational studies including a control group regarding the role of trimethoprim/sulfametoxazole (TMP/SMX) in reducing the relapse rate in patients with granulomatosis with polyangiitis (GPA) and the risk of infections in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).METHODS: MEDLINE, EMBASE, The Cochrane Library databases, Scopus, Web of Science, ClinicalTrials.gov were searched from inception until the 15th of January 2020 to identify controlled studies assessing the role of TMP/SMX in reducing the rate of relapse in patients with GPA (primary outcome) and the number and/or severity of infections in patients with AAV (secondary outcome). Two reviewers independently selected eligible studies and extracted data. Cumulative risk ratios (RR) with 95% confidence interval (CI) were calculated using a random effect meta-analysis.RESULTS: Eight studies were selected out of 2907 records. Seven studies (520 patients) (of which two RCT) assessed the role of TMP/SMX on the relapse rate in patients with GPA. TMP/SMX was not associated with a reduced risk of relapse (RR 1.15; 95% CI 0.51-2.55; I2=78.5%, p< 0.001). Sensitivity analysis according to the dose of TMP/SMX (960mg twice daily vs three-times/week) confirmed the results. One retrospective cohort study (192 patients) was identified demonstrating a significant reduction of severe infections in patients with AAV receiving prophylaxis with TMP/SMX in association with rituximab.CONCLUSION: TMP/SMX was not associated with a reduced risk of relapse in patients with GPA. TMP/SMX might be useful in the reduction of infectious complications.