Background Pneumocystis pneumonia (PCP) is a significant cause of morbidity and mortality in patients with rheumatic diseases, especially in the case of patients receiving high-dose steroid treatment.
Objectives To investigate the efficacy and safety of PCP prophylaxis using trimethoprim/sulfamethoxazole (TMP-SMX) in patients with rheumatic disease receiving prolonged, high-dose steroids
Methods This study includes 1522 cases of prolonged (≥4 weeks), high-dose (≥30mg/day prednisone or equivalent) steroid treatment from 1092 patients with any rheumatic diseases during a 12-year period in a single tertiary referral center in South Korea. Of them, prophylactic TMP-SMX was administered in 262 cases (prophylaxis group) with a mean (SD) duration of 229.0 (272.7) days whereas other 1260 cases received no prophylaxis (control group). Primary outcome was 1-year incidence of PCP between the two groups. Secondary outcomes included PCP-related mortality, ICU admission rate, all-cause in-hospital mortality and incidence of any adverse drug reactions (ADRs) of TMP-SMX. To minimize the baseline imbalance between the two groups, we introduced propensity-score matching and performed the same analysis in the post-matched population as a sensitivity analysis.
Results Patients in the prophylaxis group were treated more often with secondary immunosuppressive drugs and had a higher proportion of patients with PCP high-risk diseases (ANCA-associated vasculitis and dermatomyositis) and lymphopenia at baseline. Overall, 30 cases of PCP occurred and resulted in death in 11 cases (36.7%). In the prophylaxis group, only one non-fatal case of PCP occurred. One-year PCP incidence was significantly lower in the prophylaxis group (adjusted HRs=0.096 [0.013–0.719]) (Figure). TMP-SMX also significantly reduced the PCP-related mortality (adjusted HR=0.101 [0.001–0.809]) whereas ICU admission rate and in-hospital mortality rate were not different between the two groups during the observation. This result was consistent in the sensitivity analysis where same analysis was performed in the post-matched population.
Thirty-four cases of ADRs of TMP-SMX occurred, with an incidence rate (95% CI) of 24.2 (17.3–33.0) per 100 person-year. There were two cases of serious ADR (one pancytopenia and one Steven's Johnson syndrome) but they all recovered shortly after the discontinuation of TMP-SMX. The number needed to harm (NNH) of serious ADR was 109 whereas the number needed to treat (NNT) to prevent one case of PCP in the whole population was 52.
Conclusions In patients with rheumatic disease receiving prolonged, high-dose steroid treatment, TMP-SMX prophylaxis significantly lower the incidence of PCP with favorable safety.
Stern A, Green H, Paul M, Vidal L, Leibovici L. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients. The Cochrane database of systematic reviews. 2014(10):CD005590.
Disclosure of Interest None declared