Date: Sunday, November 5, 2017
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PCP), but is sometimes discontinued due to adverse events (AEs). We have previously reported the results of this non-blinded, randomized, non-inferiority trial up to week 24 to explore an effective SMX/TMP regimen for PCP with a low drug discontinuation (d/c) rate. We here report the results at week 52.
Methods: Adult patients with systemic rheumatic diseases who started prednisolone >0.6 mg/kg/day were randomized into three groups and treated up to week 24: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, raising incrementally to 200/40 mg daily). After week 24, attending physicians determined the use of SMX/TMP including doses, intervals, and treatment duration. The observation period was up to week 52 irrespective of the use of SMX/TMP. The primary endpoint was non-incidence rates (non-IR) of PCP at week 24. Secondary endpoints were PCP non-incidence rate at week 52, treatment d/c rate, and AEs. We estimated the non-incidence rates of PCP using the exact confidence interval as a post-hoc analysis and analyzed treatment d/c rates using the Kaplan-Meier method and log-rank test.
Results: Of 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP and were analyzed. Of the 172 patients who started SMX/TMP, 32, 46, and 38 at week 24, and 29, 43, and 34 at week 52 were receiving SMX/TMP as allocated. No cases of PCP were reported up to week 52. Estimated non-IR of PCP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8–100%. From week 0 to 52, the overall d/c rate was significantly lower in HS compared to that in SS (22.7% vs 47.2%, p = 0.004) (Figure). The d/c rates due to AEs were significantly lower in HS (19.1%, p = 0.007) and ES (20.3%, p = 0.007) compared to that in SS (41.8%). The IR of AEs requiring dose reduction of SMX/TMP (p = 0.007) and AEs of special interest (p = 0.001) at week 52 were different among the three groups with significantly higher IR in SS compared to HS and ES. Almost all AEs requiring dose reduction of SMX/TMP and AEs of special interest were reported by week 24.
Conclusion: The combined group of HS and ES had an excellent estimated non-IR of PCP at week 52 and both were superior in safety to SS. From the perspective of feasibility and drug d/c rates, the daily half-strength regimen is suggested to be optimal for prophylaxis of PCP in patients with systemic rheumatic diseases.
To cite this abstract in AMA style:Harigai M, Utsunomiya M, Dobashi H, Odani T, Saito K, Yokogawa N, Nagasaka K, Takenaka K, Soejima M, Sugihara T, Hagiyama H, Hirata S, Matsui K, Nonomura Y, Kondo M, Suzuki F, Tomita M, Kihara M, Yokoyama W, Hirano F, Yamazaki H, Sakai R, Nanki T, Koike R, Kohsaka H, Miyasaka N. Optimal Regimens of Sulfamethoxazole-Trimethoprim for Chemoprophylaxis of Pneumocystis Pneumonia in Patients with Systemic Rheumatic Diseases: 52-Week Follow-up of a Non-Blinded, Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/optimal-regimens-of-sulfamethoxazole-trimethoprim-for-chemoprophylaxis-of-pneumocystis-pneumonia-in-patients-with-systemic-rheumatic-diseases-52-week-follow-up-of-a-non-blinded-randomized-controlled/. Accessed May 29, 2020.
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