Background & Aims

The long-term efficacy and safety of upadacitinib was evaluated in an open-label extension (OLE) of a phase II, double-blind, randomized trial of patients with Crohn’s disease.

Methods

Patients who completed the 52-week study (CELEST) received upadacitinib in the CELEST OLE as follows: those who had received immediate-release upadacitinib 3, 6, or 12 mg twice daily or 24 mg once daily (QD) received extended-release upadacitinib 15 mg QD and those who had received immediate-release upadacitinib 12 or 24 mg twice daily as rescue therapy received extended-release upadacitinib 30 mg QD. If any patient initiating upadacitinib 15 mg QD in CELEST OLE lost response at or after week 4, the dose was escalated to upadacitinib 30 mg QD (dose-escalated group). Clinical, endoscopic, inflammatory and quality-of-life measures were assessed.

Results

A total of 107 CELEST study completers entered CELEST OLE. The proportion of patients with clinical remission 2.8/1.0 was maintained between week 0 and month 30 in all groups (month 30: 15 mg, 61%; 30 mg, 54%; dose-escalation, 55%). Endoscopic response was maintained in all groups (month 24: 68%, 67%, and 40%, respectively). The rates of adverse events (AEs), serious AEs, AEs leading to discontinuation, infections, serious infections, herpes zoster, and creatine phosphokinase elevation were higher with upadacitinib 30 mg vs 15 mg.

Conclusion

Sustained long-term benefit at 30 months and further endoscopic improvements to month 24 were observed in patients with Crohn’s disease receiving upadacitinib. Safety over 30 months was consistent with the known safety profile of upadacitinib. Clinicaltrials.gov ID no: NCT02782663.

中文翻译：

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在 CELEST 扩展研究中，Upadacitinib 在克罗恩病患者中有效且耐受性良好超过 30 个月

背景与目标

upadacitinib 的长期疗效和安全性在一项针对克罗恩病患者的 II 期、双盲、随机试验的开放标签扩展 (OLE) 中进行了评估。

方法

完成 52 周研究 (CELEST) 的患者在 CELEST OLE 中接受 upadacitinib 如下：接受速释 upadacitinib 3、6 或 12 mg 每日两次或 24 mg 每日一次 (QD) 的患者接受缓释 upadacitinib 15 mg QD 和接受速释 upadacitinib 12 或 24 mg 每日两次作为挽救治疗的患者接受缓释 upadacitinib 30 mg QD。如果在 CELEST OLE 中开始使用 upadacitinib 15 mg QD 的任何患者在第 4 周或之后失去反应，则将剂量升级至 upadacitinib 30 mg QD（剂量递增组）。评估了临床、内窥镜、炎症和生活质量指标。

结果

共有 107 名 CELEST 研究完成者进入 CELEST OLE。在所有组中，临床缓解率为 2.8/1.0 的患者比例在第 0 周和第 30 个月之间保持不变（第 30 个月：15 mg，61%；30 mg，54%；剂量递增，55%）。所有组均维持内镜反应（第 24 个月：分别为 68%、67% 和 40%）。upadacitinib 30 mg 与 15 mg 的不良事件 (AE)、严重 AE、导致停药、感染、严重感染、带状疱疹和肌酸磷酸激酶升高的发生率较高。

结论

在接受 upadacitinib 治疗的克罗恩病患者中，观察到在 30 个月时持续的长期获益和到第 24 个月时的进一步内镜改善。超过 30 个月的安全性与已知的 upadacitinib 安全性一致。Clinicaltrials.gov ID 号：NCT02782663。