Objective To assess the association of trimethoprim sulfamethoxazole (TMP-SMX) prophylaxis with serious infections in rituximab-treated patients with granulomatosis with polyangiitis (GPA). Methods This retrospective cohort study included adults with GPA (2011–2020) within the United States Merative™ Marketscan® Research Databases with ≥6 months enrolment prior to first (index) rituximab treatment. We defined TMP-SMX prophylaxis as a ≥28-day prescription dispensed after or overlapping the index date. Serious infection was a hospital primary diagnosis for infection (excluding viral or mycobacterial codes). Secondary outcomes were outpatient infection, PJP, and adverse events potentially attributable to TMP-SMX. Cox proportional hazards regression assessed the association of time-varying TMP-SMX with outcomes of interest, adjusting for potential confounders. Individuals were followed until the outcome of interest, end of database enrolment, or Dec 31, 2020. Results Among 919 rituximab-treated individuals (53% female), mean age was 52.1 years (SD 16) and 281 (31%) were dispensed TMP-SMX within 30 days of index date. Over a median of 496 (IQR 138, 979) days, 130 serious infections occurred among 104 individuals (incidence 6.1 [95% CI 5.0–7.4] per 100 person-years). Time-varying TMP-SMX was negatively associated with serious infection (adjusted HR 0.5; 95% CI 0.3–0.9). The aHR for outpatient infections was 0.8 (95% CI 0.6–1.1). The estimate for PJP was imprecise (13 events, unadjusted HR 0.2; 95% CI 0.03–1.8). TMP-SMX was potentially associated with adverse events (aHR 1.3; 95% CI 0.9–1.9). Conclusions TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of optimal prophylaxis strategies.

中文翻译：

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甲氧苄氨嘧啶磺胺甲恶唑预防和利妥昔单抗治疗肉芽肿性多血管炎的严重感染


目的 评估甲氧苄啶磺胺甲恶唑 (TMP-SMX) 预防与利妥昔单抗治疗的肉芽肿性多血管炎 (GPA) 患者严重感染的关系。方法 这项回顾性队列研究纳入了美国 Merative™ Marketscan® 研究数据库中具有 GPA (2011-2020) 的成年人，且在首次（指数）利妥昔单抗治疗前入组时间≥6 个月。我们将 TMP-SMX 预防定义为在索引日期之后或与索引日期重叠的 ≥28 天的处方。严重感染是医院感染的初步诊断（不包括病毒或分枝杆菌代码）。次要结局是门诊感染、PJP 和可能由 TMP-SMX 引起的不良事件。 Cox 比例风险回归评估了时变 TMP-SMX 与感兴趣结果的关联，并调整了潜在的混杂因素。对个体进行随访，直至出现感兴趣的结果、数据库登记结束或 2020 年 12 月 31 日。结果 在 919 名接受利妥昔单抗治疗的个体（53% 女性）中，平均年龄为 52.1 岁（SD 16），其中 281 名患者（31%）被分配TMP-SMX 在索引日期后 30 天内。在中位数 496 (IQR 138, 979) 天的时间里，104 人中发生了 130 例严重感染（发病率为每 100 人年 6.1 [95% CI 5.0–7.4]）。时变 TMP-SMX 与严重感染呈负相关（调整后 HR 0.5；95% CI 0.3-0.9）。门诊感染的 aHR 为 0.8（95% CI 0.6-1.1）。 PJP 的估计不精确（13 个事件，未经调整的 HR 0.2；95% CI 0.03–1.8）。 TMP-SMX 可能与不良事件相关（aHR 1.3；95% CI 0.9–1.9）。 结论 TMP-SMX 预防与利妥昔单抗治疗的 GPA 严重感染减少相关，但可能增加不良事件，需要进一步研究最佳预防策略。