Ozanimod induction therapy for patients with moderate to severe Crohn's disease: a single-arm, phase 2, prospective observer-blinded endpoint study
Ozanimod induction therapy for patients with moderate to severe Crohn's disease: a single-arm, phase 2, prospective observer-blinded endpoint study
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DOI：
10.1016/s2468-1253(20)30188-6
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发表时间：
2020-09-01
影响因子：
35.7
通讯作者：
D'Haens, Geert
中科院分区：
文献类型：
--
作者：
Feagan, Brian G.;Sandborn, William J.;D'Haens, Geert
背景尽管随着肿瘤坏死因子拮抗剂的开发，克罗恩病的治疗有所改善，但只有不到 50% 的患者能够持续受益。口服替代治疗的持久维持治疗的需求仍未得到满足。我们的目的是评估 ozanimod（一种选择性靶向 1-磷酸鞘氨醇受体亚型 1 和 5 的口服药物）对克罗恩病内窥镜疾病活动的影响。方法 STEPSTONE 是一项 2 期、非对照、多中心试验，受试者为中度至重度活动性克罗恩病成人，招募对象为加拿大、美国、匈牙利、波兰和乌克兰的 28 家医院和社区研究中心。所有患者均开始接受 7 天剂量递增治疗（奥扎莫德 4 天，每天 0.25 mg，随后 3 天，每天 0.5 mg）。然后患者每天接受 ozanimod 1.0 mg 口服胶囊，持续 11 周，即 12 周诱导期，随后延长 100 周。主要终点是克罗恩病简单内窥镜评分 (SES-CD) 从基线到第 12 周的变化，由盲法中心阅片员确定。报告意向治疗人群的数据。该试验已在 ClinicalTrials.gov 注册（编号为 NCT02531113）和 EudraCT（编号为 2015-002025-19），并已完成。结果 2015 年 11 月 17 日至 2016 年 8 月 18 日期间入组了 69 名患者。第 12 周时，SES-CD 相对于基线的平均变化为 -2.2 (SD 6.0)； 16 名（23.2%，95% CI 13.9-34.9）患者出现内镜缓解。还观察到克罗恩病活动指数 (CDAI) 评分较基线有所下降（平均变化 -130.4 [SD 103.9]）。临床缓解（CDAI
Background Although treatment of Crohn's disease has improved with development of tumour necrosis factor antagonists, fewer than 50% of patients have sustained benefit. Durable maintenance therapy with orally administered alternative treatments remains an unmet need. We aimed to evaluate the effects of ozanimod, an oral agent selectively targeting sphingosine-1-phosphate receptor subtypes 1 and 5, on endoscopic disease activity in Crohn's disease.Methods STEPSTONE was a phase 2, uncontrolled, multicentre trial in adults with moderately to severely active Crohn's disease recruited at 28 hospital and community research centres in Canada, the USA, Hungary, Poland, and Ukraine. All patients began treatment with a 7-day dose escalation (4 days on ozanimod 0.25 mg daily followed by 3 days at 0.5 mg daily). Patients then received ozanimod 1.0 mg oral capsule daily for a further 11 weeks, for a 12-week induction period, followed by a 100-week extension. The primary endpoint was change in Simple Endoscopic Score for Crohn's Disease (SES-CD) from baseline to week 12, as determined by a blinded central reader. Data are reported for the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT02531113 and EudraCT, number 2015-002025-19, and is completed.Findings 69 patients were enrolled between Nov 17, 2015, and Aug 18, 2016. At week 12, the mean change from baseline in SES-CD was -2.2 (SD 6.0); 16 (23.2%, 95% CI 13.9-34.9) patients experienced endoscopic response. A reduction from baseline in Crohn's Disease Activity Index (CDAI) score also was observed (mean change -130.4 [SD 103.9]). Clinical remission (CDAI