Department of Gastroenterology, Henri Mondor Hospital, Assistance Publique - Hôpitaux de Paris, EC2M3-Equipe Universitaire, Paris Est-Créteil Val de Marne University, Creteil, France.
Hôpital Nord, Centre d'Investigation Clinique Marseille Nord, Université Méditerranée, Marseille, France.
Clin Gastroenterol Hepatol. 2016 Nov;14(11):1593-1601.e2. doi: 10.1016/j.cgh.2016.02.016. Epub 2016 Feb 22.
BACKGROUND & AIMS: Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy.
From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase.
Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma).
In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients.
已有研究表明，靶向整合素 α4β7 的维多珠单抗在克罗恩病（CD）或溃疡性结肠炎（UC）患者中具有疗效。我们旨在评估维多珠单抗在抗 TNF 治疗失败的患者中的有效性和安全性。
2014 年 6 月至 12 月，173 例 CD 患者和 121 例 UC 患者参与了一项由法国监管机构批准的多中心、指定、同情性早期准入计划，该计划允许患者在维多珠单抗获得上市批准之前使用该药。患者接受静脉注射维多珠单抗（300mg），剂量方案为：第 0、2、6 周各给药 1 次，之后每 8 周给药 1 次。CD 患者采用 Harvey-Bradshaw 指数评估疾病活动度，UC 患者采用部分 Mayo 评分评估疾病活动度。本研究报告了诱导期 14 周后的结果。
294 例接受维多珠单抗治疗的患者（平均年龄为 39.5±14.0 岁；平均病程为 10.8±7.6 年；同时使用皮质类固醇者占 44%）中，276 例患者完成了诱导期治疗，但有 18 例患者因无应答（n=14）、输注相关反应（n=2）或感染（n=2）而停用维多珠单抗。治疗 14 周后，31%的 CD 患者达到无皮质类固醇的临床缓解，51%的患者有应答；UC 患者中，36%达到无皮质类固醇的临床缓解，50%的患者有应答。无死亡病例报告。24 例（8.2%）患者发生严重不良事件，其中 15 例（5.1%）导致维多珠单抗停药（1 例肺结核和 1 例直肠腺癌）。
在抗 TNF 治疗失败的 CD 或 UC 患者中，维多珠单抗诱导治疗 14 周后，约有 1/3 的患者达到无皮质类固醇的临床缓解。该药物在这些患者中的安全性良好。
