The role of trimethoprim/sulfametoxazole in reducing relapses and risk of infections in ANCA-associated vasculitis: a meta-analysis

Objectives: To assess available evidence from randomized controlled trials (RCTs) 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 ANCA-associated vasculitis (AAV). Methods: MEDLINE, EMBASE, The Cochrane Library databases, Scopus, Web of Science and ClinicalTrials.gov were searched from inception until 15 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 (RRs) with 95% 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 were RCTs) assessed the role of TMP/SMX in 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 (960 mg 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. Prospero database registration code: CRD42019118983.