乌帕替尼治疗对中度至重度克罗恩病患者的生活质量和工作生产力的改善：来自 2b 期的证据。

Quality of Life and Work Productivity Improvements with Upadacitinib: Phase 2b Evidence from Patients with Moderate to Severe Crohn's Disease.

机构信息

Department of Gastroenterology, Nancy University Hospital, Nancy, France.

Université de Lorraine, Nancy, France.

出版信息

Adv Ther. 2021 May;38(5):2339-2352. doi: 10.1007/s12325-021-01660-7. Epub 2021 Mar 23.

DOI:10.1007/s12325-021-01660-7

PMID:33755884

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8107073/

Abstract

INTRODUCTION

In the phase 2 CELEST study, positive efficacy results were obtained with the Janus kinase 1 inhibitor upadacitinib for adult patients with moderate to severe Crohn's disease. We present the health-related quality of life and work productivity improvement results with upadacitinib from CELEST.

METHODS

CELEST (NCT02365649) was a double-blind study where patients were randomized 1:1:1:1:1:1 in the 16-week induction period to placebo or upadacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg BID, 24 mg BID, or 24 mg once daily (QD). Patients completing the induction period were re-randomized 1:1:1 to receive upadacitinib 3 mg BID, 12 mg BID, or 24 mg QD for 36 weeks or 3 mg BID, 6 mg BID, or 12 mg BID (after amendment). Inflammatory Bowel Disease Questionnaire (IBDQ), European Quality of Life-5 Dimensions visual analog scale (EQ-5D VAS), and Work Productivity and Activity Impairment (WPAI) questionnaire outcomes were assessed at baseline and Weeks 8, 16, and 52.

RESULTS

At Week 16, a significant percentage (P ≤ 0.05) of patients receiving upadacitinib 6-mg BID dose or higher achieved IBDQ response (IBDQ score change ≥ 16 points; 49%-57% for upadacitinib vs. 24% for placebo) and IBDQ remission, except 24 mg QD (IBDQ score ≥ 170; 26%-39% for upadacitinib vs. 11% for placebo). Greater improvements in IBDQ total score, EQ-5D VAS, and activity impairment from baseline (P ≤ 0.1) versus placebo were also observed. Larger improvements (P ≤ 0.1) in IBDQ response and total score and EQ-5D VAS were observed at Week 8 with 6 and 24 mg BID versus placebo, with improvements for all dosages maintained or greater at Week 52 for IBDQ, EQ-5D VAS, and WPAI endpoints, in particular for the 12-mg BID group.

CONCLUSION

Improvements in health-related quality of life and work productivity were achieved and sustained with upadacitinib in patients with moderate to severe Crohn's disease.

TRIAL REGISTRATION

ClinicalTrials.gov identifier, NCT02365649.

摘要

简介

在 2 期 CELEST 研究中，Janus 激酶 1 抑制剂 upadacitinib 对中重度克罗恩病成年患者显示出积极的疗效。我们在此展示 CELEST 中 upadacitinib 带来的健康相关生活质量和工作生产力改善结果。

方法

CELEST（NCT02365649）是一项双盲研究，16 周诱导期内，患者按 1:1:1:1:1:1 的比例随机分配至安慰剂或 upadacitinib 3mg 每日 2 次（BID）、6mg BID、12mg BID、24mg BID 或 24mg 每日 1 次（QD）。完成诱导期的患者按 1:1:1:1 的比例再随机分配至 upadacitinib 3mg BID、12mg BID 或 24mg QD 治疗 36 周，或 3mg BID、6mg BID 或 12mg BID（经修订后）。在基线和第 8、16、52 周时评估炎症性肠病问卷（IBDQ）、欧洲五维健康量表视觉模拟评分（EQ-5D VAS）和工作生产力和活动障碍（WPAI）问卷结果。

结果

在第 16 周时，接受 upadacitinib 6mg BID 或更高剂量治疗的患者达到 IBDQ 应答（IBDQ 评分变化≥16 分；upadacitinib 为 49%-57%，安慰剂为 24%）和 IBDQ 缓解的比例显著更高（P≤0.05），除了 24mg QD（IBDQ 评分≥170；upadacitinib 为 26%-39%，安慰剂为 11%）。与安慰剂相比，IBDQ 总分、EQ-5D VAS 和活动障碍的改善也具有显著统计学意义（P≤0.1）。与安慰剂相比，第 8 周时，6mg 和 24mg BID 时也观察到 IBDQ 应答和总分以及 EQ-5D VAS 的更大改善（P≤0.1），所有剂量组在第 52 周时 IBDQ、EQ-5D VAS 和 WPAI 终点的改善得以维持或进一步改善，特别是在 12mg BID 组。