伊特拉西莫和奥扎莫治疗中重度活动性溃疡性结肠炎疗效的间接比较。

IF 1.9 4区 医学 Q3 HEALTH CARE SCIENCES & SERVICES
Vipul Jairath, Tim Raine, Thomas P Leahy, Ravi Potluri, Karolina Wosik, David Gruben, Joseph C Cappelleri, Peter Hur, Lauren Bartolome
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引用次数: 0

摘要

目的:Etrasimod和ozanimod是选择性鞘氨醇1-磷酸受体调节剂,分别靶向S1P1,4,5和S1P1,5受体,用于治疗中度至重度活动性溃疡性结肠炎(UC)患者。两种治疗方法之间没有直接的试验数据。我们使用关键试验的关键疗效结果与诱导和维持期数据间接比较了这些治疗方法,调整了临床试验设计和人群的差异。材料和方法:通过关键基线特征将etrasimod的个体患者数据与ozanimod已发表的总体数据相匹配。在诱导期进行锚定匹配调整间接比较(MAIC)。由于不同的试验设计导致安慰剂组在试验之间存在差异,因此在维持期间使用了非锚定的MAIC。基线时测量的匹配特征是年龄、性别、皮质类固醇使用、UC持续时间、生物暴露、改良Mayo评分和左侧结肠炎的存在。结果为诱导期的临床反应和临床缓解,维持期诱导期应答者的临床反应和临床缓解。进行了两次敏感性分析。第一次与先前的TNFi暴露而不是生物暴露相匹配,第二次敏感性分析包括仅诱导的伊特拉西莫试验(ELEVATE UC 12)。结果:在诱导期结束时,etrasimod与ozanimod的临床反应和临床缓解差异均无统计学意义(相对危险度[RR] 0.98[95%可信区间(CI): 0.76-1.33], RR: 1.25 [95% CI: 0.71-2.92])。在维持期结束时,与ozanimod相比,etrasimod在诱导期应答者的临床反应(RR: 1.18 [95% CI: 1.05-1.30])和临床缓解(RR: 1.33 [95% CI: 1.12-1.55])方面均表现出改善的结果。在敏感性分析中,匹配先前的TNFi暴露而不是生物暴露,与主要分析相比没有显着差异。在汇集ELEVATE UC 12和ELEVATE UC 52数据的敏感性分析中,临床反应的结果相似(RR: 0.90 [95% CI: 0.75-1.10]),但与主要分析相比,伊特拉西莫对临床缓解的疗效降低(RR: 0.72 [95% CI: 0.50-1.12]),尽管总体上与ozanimod没有显著差异。结论:MAIC结果提示,与接受奥扎尼莫相比,接受伊特拉西莫的患者具有相似的诱导结果,但在维持期结束时更有可能出现临床反应和临床缓解。尽管该方法通过加权确保试验之间的相似性,但残余不平衡是可能的,结果应在假设的背景下解释。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Matching-adjusted indirect comparisons of efficacy outcomes between etrasimod and ozanimod for moderately to severely active ulcerative colitis.

Aim: Etrasimod and ozanimod are selective sphingosine 1-phosphate receptor modulators targeting the S1P1,4,5, and S1P1,5 receptors, respectively, for the treatment of patients with moderately to severely active ulcerative colitis (UC). No head-to-head trial data exist between the two treatments. We compared these treatments indirectly using key efficacy outcomes from pivotal trials with induction and maintenance phase data adjusting for differences in clinical trial design and populations. Materials & methods: Individual patient data for etrasimod were matched to published aggregate data of ozanimod by key baseline characteristics. An anchored matching-adjusted indirect comparison (MAIC) was conducted for the induction period. An unanchored MAIC was utilized during the maintenance period due to differences in placebo arms between trials as a result of differing trial designs. Matching characteristics measured at baseline were age, sex, corticosteroid use, duration of UC, biologic exposure, modified Mayo score, and presence of left-sided colitis. Outcomes were clinical response and clinical remission for the induction period, and clinical response and clinical remission among induction phase responders for the maintenance period. Two sensitivity analyses were conducted. The first matched on prior TNFi exposure rather than biologic exposure, the second sensitivity analysis included an induction only etrasimod trial (ELEVATE UC 12). Results: There were no significant differences between etrasimod and ozanimod at the end of the induction period for clinical response and clinical remission, respectively (relative risk [RR] 0.98 [95% confidence interval (CI): 0.76-1.33], RR: 1.25 [95% CI: 0.71-2.92]). At the end of maintenance, etrasimod demonstrated improved outcomes compared with ozanimod for both clinical response (RR: 1.18 [95% CI: 1.05-1.30]) and clinical remission among induction phase responders (RR: 1.33 [95% CI: 1.12-1.55]). In the sensitivity analysis that matched on prior TNFi exposure rather than biologic exposure, there were no notable differences compared with the primary analyses. In the sensitivity analysis pooling ELEVATE UC 12 and ELEVATE UC 52 data, results were similar for clinical response (RR: 0.90 [95% CI: 0.75-1.10]) but etrasimod showed reduced efficacy for clinical remission (RR: 0.72 [95% CI: 0.50-1.12]) compared with the primary analysis, though overall remained not significantly different from ozanimod. Conclusion: MAIC results suggest that patients receiving etrasimod have similar induction results but are more likely to have clinical response and clinical remission at the end of the maintenance phase compared with patients receiving ozanimod. Despite the approach to ensure similarity between the trials by weighting, residual imbalance is possible, and results should be interpreted in the context of the assumptions.

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来源期刊
Journal of comparative effectiveness research
Journal of comparative effectiveness research HEALTH CARE SCIENCES & SERVICES-
CiteScore
3.50
自引率
9.50%
发文量
121
期刊介绍: Journal of Comparative Effectiveness Research provides a rapid-publication platform for debate, and for the presentation of new findings and research methodologies. Through rigorous evaluation and comprehensive coverage, the Journal of Comparative Effectiveness Research provides stakeholders (including patients, clinicians, healthcare purchasers, and health policy makers) with the key data and opinions to make informed and specific decisions on clinical practice.
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