Pneumocystis pneumonia (PCP) is a potentially life-threatening opportunistic infection. Sulfamethoxazole–trimethoprim (SMX/TMP) is effective in preventing pneumocystis pneumonia in patients with systemic rheumatic disease. However, the frequency of adverse events (AEs) due to SMX/TMP in rheumatic disease patients is higher than in the general population. The EULAR recommendation 2022 was described as “Of note, there is some evidence that reduced doses (eg, half-strength, daily) may also be effective and associated with fewer adverse events” [1].
This study aimed to identify the optimal dose of SMX/TMP for the prophylaxis of PCP in patients with systemic rheumatic disease.
Our protocols of this study were described previously [2]. This study was a 52-week, randomized, open-label, two-arm, parallel-group, multicenter controlled trial. We compared a full-dose group (SMX/TMP at 400/80 mg daily) with a half-dose group (SMX/TMP at 200/40 mg daily). Inclusion criteria were follows: aged over 20 years; admission to our hospitals for diagnosis and/or treatment of new-onset or relapsed systemic rheumatic diseases from April 1, 2018, to March 31, 2021; current treatment with at least 0.6 mg/kg/day of oral prednisolone or equivalent doses of corticosteroids with or without any immunosuppressant; no prior treatment with SMX/TMP, pentamidine isethionate, dapsone, or atovaquone; Serum creatinine levels within the institution's normal range; Able and willing to provide written informed consent. Exclusion criteria were follows: contraindications to SMX/TMP; past history of PCP; prior treatment with biologic agents; currently uncontrollable complications; body weight below 40 kg; currently pregnant or nursing; unable to begin SMX/TMP within 14 days of starting prednisolone; unable to provide informed consent. The Mann–Whitney U test was used for non-normally distributed variables. Categorical variables were compared using Fisher's exact test. The discontinuation rate of SMP/TMP in each group was compared by plotting Kaplan–Meier survival curves and evaluating them with the log-rank test.
Forty-two patients in full-dose group and 43 patients in half-dose group were analyzed. Since all patients were not developed with PCP while taking SMX/TMP, the results of the primary outcome measure of current as the number of patients in each treatment arm who were diagnosed with PCP were both 0. The discontinuation rates were 38% in full-dose group vs 16% in half-dose group (p value = 0.028).
Half-dose regimen of TMP/SMX may be better to reduce AEs than full-dose regimen in prophylaxis for PCP in patients with systemic rheumatic disease.
[1]Fragoulis GE, Nikiphorou E, Dey M, Zhao SS, Courvoisier DS, Arnaud L, et al. 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases. Annals of the rheumatic diseases. 2022 Nov 3. https://doi.org/10.1136/ard-2022-223335
[2]Abe Y, Fujibayashi K, Nishizaki Y, Yanagisawa N, Nojiri S, Nakano S, et al. Conventional-dose Versus Half-dose Sulfamethoxazole-trimethoprim for the Prophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Disease: A Non-blind, Randomized Controlled Trial. Acta Med Okayama. 2019 Feb; 73(1):85-89.