Remo Panaccione, Christopher Ma, Vipul Jairath, Axel Dignass, Namita Joshi, Ryan Clark, Jenny Griffith, Kristina Kligys, Monika Semwal, Zachary Smith, Dominic Mitchell, Dominic Nunag, Marc Ferrante
{"title":"诱导后达到内镜缓解可减轻克罗恩病的住院负担:利桑珠单抗和乌帕他替尼III期试验的汇总后分析结果》(Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials)。","authors":"Remo Panaccione, Christopher Ma, Vipul Jairath, Axel Dignass, Namita Joshi, Ryan Clark, Jenny Griffith, Kristina Kligys, Monika Semwal, Zachary Smith, Dominic Mitchell, Dominic Nunag, Marc Ferrante","doi":"10.1093/ecco-jcc/jjae128","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD.</p><p><strong>Methods: </strong>Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm.</p><p><strong>Results: </strong>Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively.</p><p><strong>Conclusions: </strong>Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials.\",\"authors\":\"Remo Panaccione, Christopher Ma, Vipul Jairath, Axel Dignass, Namita Joshi, Ryan Clark, Jenny Griffith, Kristina Kligys, Monika Semwal, Zachary Smith, Dominic Mitchell, Dominic Nunag, Marc Ferrante\",\"doi\":\"10.1093/ecco-jcc/jjae128\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD.</p><p><strong>Methods: </strong>Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm.</p><p><strong>Results: </strong>Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively.</p><p><strong>Conclusions: </strong>Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. 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引用次数: 0
摘要
背景:内镜缓解已成为克罗恩病(CD)的一个重要治疗目标,并与长期预后的改善有关。我们对中度至重度活动性克罗恩病患者进行了为期 52 周的利桑珠单抗和乌达替尼维持治疗 III 期试验,研究了内镜缓解与住院治疗之间的关系:纳入的患者在使用利桑珠单抗或高达替尼进行为期 12 周的诱导治疗并获得临床应答后接受维持治疗。内镜下缓解的定义是:CD简单内镜评分不超过4分,与诱导基线相比至少降低2分,且没有子评分超过1分。在控制人口统计学、临床变量和治疗组的情况下,对暴露调整负二项回归模型进行了估计,以评估诱导后内镜缓解与长期住院之间的关系:结果:在诱导期结束时获得内镜缓解的患者诱导后住院率较低。在多变量模型中,诱导后内镜缓解与长期疾病相关住院和全因住院的IRR分别为0.45(95% CI [0.22-0.95],p=0.036)和0.71(95% CI [0.44-1.14],p=0.156):结论:第12周内镜治疗缓解与减少52周疾病相关住院率密切相关。结论:第12周内镜下缓解与减少52周疾病相关住院率密切相关。然而,在治疗12周内达到这一严格终点可能具有挑战性。内镜反应可能是诱导后更现实的早期内镜目标。还需要进行更多的研究来评估 CD 早期实现其他内镜终点的情况。
Achievement of Endoscopic Remission After Induction Reduces Hospitalization Burden in Crohn's Disease: Findings From a Pooled Post Hoc Analysis of Risankizumab and Upadacitinib Phase III Trials.
Background: Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD.
Methods: Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm.
Results: Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively.
Conclusions: Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD.