Kim Yun Kyu, Curtis Jeffrey R, Choi Se Rim, Yeo Jina, Kim Min Jung, Lee Yun Jong, Lee Eun Bong, Park Jun Won
Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama.
Arthritis Rheumatol. 2025 Apr 14. doi: 10.1002/art.43185.
The objective of this study was to investigate the effect of prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) on the incidence of serious infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).
This multicenter cohort study was designed to emulate a target trial that studied 296 patients with AAV who were treated with rituximab (RTX) or cyclophosphamide (CYC) as induction therapy. Patients were grouped based on the administration of TMP-SMX within 14 days following induction therapy (n = 240 and 56 patients in prophylaxis and control groups, respectively) (intention-to-treat) and also as a time-dependent exposure (time-varying). Inverse probability weighting was applied to minimize the baseline imbalance between the two groups. The primary outcome was one-year incidence of serious infection.
During the 252.1 person-years of observation, 77 cases of serious infections were recorded in 65 patients with a fatality rate of 18.5%. Most serious infections (n = 66, 85.7%) occurred within the first 180 days of observation. The prophylaxis group showed a significantly lower incidence of serious infections than the control group (hazard ratio [HR] 0.48 [95% confidence interval (CI) 0.32-0.72]). However, this beneficial effect of TMP-SMX was only significant during the first 180 days (HR 0.41 [95% CI 0.22-0.76]) and not thereafter (HR 3.67 [95% CI 0.46-29.43]) (interaction P = 0.044). This result was also consistent with the time-varying analysis result. Based on one case of severe adverse drug reaction related to TMP-SMX, the number needed to harm was 127.4, whereas the number needed to treat to prevent one serious infection was 8.0.
Prophylactic TMP-SMX significantly reduced the risk of serious infections in patients with AAV, particularly during the first six months of induction therapy with RTX or CYC.
本研究旨在探讨预防性使用甲氧苄啶-磺胺甲恶唑（TMP-SMX）对抗中性粒细胞胞浆抗体相关性血管炎（AAV）患者严重感染发生率的影响。
本多中心队列研究旨在模拟一项目标试验，该试验研究了296例接受利妥昔单抗（RTX）或环磷酰胺（CYC）作为诱导治疗的AAV患者。患者根据诱导治疗后14天内是否使用TMP-SMX进行分组（预防组和对照组分别为240例和56例患者）（意向性分析），并作为时间依赖性暴露因素（随时间变化）。应用逆概率加权法以尽量减少两组之间的基线不平衡。主要结局是严重感染的一年发生率。
在252.1人年的观察期内，65例患者记录了77例严重感染，死亡率为18.5%。大多数严重感染（n = 66，85.7%）发生在观察的前180天内。预防组严重感染的发生率显著低于对照组（风险比[HR] 0.48 [95%置信区间（CI）0.32 - 0.72]）。然而，TMP-SMX的这种有益效果仅在最初180天内显著（HR 0.41 [95% CI 0.22 - 0.76]），之后则不显著（HR 3.67 [95% CI 0.46 - 29.43]）（交互作用P = 0.044）。该结果也与随时间变化的分析结果一致。基于1例与TMP-SMX相关的严重药物不良反应，伤害所需人数为127.4，而预防1例严重感染所需治疗人数为8.0。
预防性使用TMP-SMX可显著降低AAV患者严重感染的风险，尤其是在使用RTX或CYC进行诱导治疗的前六个月。
