Department of Veterans Affairs, Edward Hines Jr Veterans Affairs Hospital, Illinois.
Gastroenterology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Clin Infect Dis. 2018 Aug 16;67(5):649-656. doi: 10.1093/cid/ciy171.
Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI.
The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented.
The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI.
The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit.
NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).
贝洛妥珠单抗是一种针对艰难梭菌毒素 B 的人源单克隆抗体，用于预防复发性艰难梭菌感染（rCDI）高危成人的艰难梭菌感染（CDI）复发（rCDI）。这项针对艰难梭菌治疗的单克隆抗体的事后分析（MODIFY）I/II 数据评估了贝洛妥珠单抗在与 rCDI 风险增加相关的特征的参与者中的疗效。
分析人群为接受贝洛妥珠单抗或安慰剂治疗的改良意向治疗人群（n=1554），其 rCDI 风险因素是根据统计分析计划预先指定的：年龄≥65 岁、CDI 病史、免疫受损、严重 CDI 和 027/078/244 核糖型。12 周时 rCDI 的参与者比例、粪便微生物群移植程序、30 天全因和 CDI 相关的住院再入院以及随机分组后 30 和 90 天的死亡率。
大多数入组参与者（75.6%）有≥1 个风险因素；与无风险因素的参与者相比，这些参与者年龄较大，合并症比例较高。每个风险因素的安慰剂参与者发生 rCDI 的比例超过 30%，而无风险因素的参与者为 20.9%，rCDI 发生率随风险因素数量的增加而增加（1 个风险因素：31.3%；≥3 个风险因素：46.1%）。贝洛妥珠单抗降低了 rCDI、粪便微生物群移植和 rCDI 相关的 30 天再入院风险因素的参与者。
MODIFY 统计分析计划中预先指定的风险因素适合识别 rCDI 高危患者。虽然有≥3 个风险因素的参与者接受贝洛妥珠单抗治疗后 rCDI 减少最多，但有 1 或 2 个风险因素的参与者也可能受益。
NCT01241552（MODIFY I）和 NCT01513239（MODIFY II）。
