An open-label, randomized controlled trial of sulfamethoxazole-trimethoprim for prophylaxis: results of 52-week follow-up.

Objectives: The aim was to investigate the long-term prophylactic efficacy, drug retention and safety of low-dose sulfamethoxazole-trimethoprim (SMX/TMP) prophylaxis against pneumonia (PCP).

Methods: Adult patients with rheumatic diseases receiving prednisolone ≥0.6 mg/kg/day were randomized into the single-strength group (SS; SMX/TMP 400/80 mg daily), the half-strength group (HS; 200/40 mg daily) or the escalation group (ES; starting at 40/8 mg and increasing incrementally to 200/40 mg daily) and treated for 24 weeks, then observed for 52 weeks. The primary endpoint, the PCP non-incidence rate (non-IR) at week 24, has been reported previously. The secondary endpoints were the PCP non-IR at week 52, treatment discontinuation rate and adverse events.

Results: Fifty-eight, 59 and 55 patients in the SS, HS and ES, respectively, received SMX/TMP. PCP did not develop in any of the patients by week 52. The estimated PCP non-IR in patients receiving SMX/TMP 200/40 mg daily (HS and ES) was 96.8-100%. Throughout the 52-week observation period, the overall discontinuation rate was significantly lower in HS than in SS (22.7 47.2%,  = 0.004). The discontinuation rates attributable to adverse events were significantly lower in HS (19.1%,  = 0.007) and ES (20.3%,  = 0.007) than in SS (41.8%). The IRs of adverse events requiring SMX/TMP dose reduction before week 52 differed among the three groups, with a significantly higher IR in SS than in HS or ES ( = 0.007).

Conclusion: SMX/TMP 200/40 mg had a high PCP prevention rate and was superior to SMX/TMP 400/80 mg in terms of drug retention and safety.

Trial Registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000007727.