Neeraj Narula, Hasan Hamam, Jasmine Liu, Emily C L Wong, John K Marshall, Vipul Jairath, Stephen B Hanauer, Walter Reinisch, Parambir S Dulai
{"title":"在溃疡性结肠炎的临床试验中,与强制减量相比,适应性类固醇减量会阻碍无皮质类固醇缓解。","authors":"Neeraj Narula, Hasan Hamam, Jasmine Liu, Emily C L Wong, John K Marshall, Vipul Jairath, Stephen B Hanauer, Walter Reinisch, Parambir S Dulai","doi":"10.1093/ecco-jcc/jjae092","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>It is unclear if steroid tapering protocols can affect clinical trial outcomes in ulcerative colitis [UC], particularly fixed versus adaptive steroid tapering. Fixed steroid tapering involves incremental dose decreases at prespecified intervals, and adaptive steroid tapering uses investigator discretion as determined by the patient's response.</p><p><strong>Methods: </strong>In this post-hoc analysis from six clinical trials of UC [VARSITY, ACT 1, PURSUIT, GEMINI1, OCTAVE, and ULTRA2], responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for treat-through versus re-randomisation designs, and multivariate regression was performed to account for other potential confounding variables. The primary outcome was corticosteroid-free clinical remission [CR] at 1 year, and secondary outcomes were CR and endoscopic improvement.</p><p><strong>Results: </strong>There was a total of 861 patients who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid tapering regimens were less likely to achieve corticosteroid-free CR at 1 year (odds ratio [OR] 0.66 [95% confidence interval, CI, 0.48-0.92], p = 0.015) but had increased odds for achieving CR at 1 year (OR 1.9 [95% CI 1.43-2.52], p < 0.001). The steroid tapering regimen was not associated with achievement of endoscopic improvement at 1 year.</p><p><strong>Conclusions: </strong>Among patients with UC on corticosteroids in clinical trials, patients using adaptive steroid weaning regimens were less likely to achieve corticosteroid-free CR at 1 year but more likely to achieve CR at 1 year. Consideration should be given to implementing mandatory fixed steroid weaning protocols in future clinical trials of UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532608/pdf/","citationCount":"0","resultStr":"{\"title\":\"Adaptive Steroid Tapering Impedes Corticosteroid-free Remissions Compared with Forced Tapering in Clinical Trials of Ulcerative Colitis.\",\"authors\":\"Neeraj Narula, Hasan Hamam, Jasmine Liu, Emily C L Wong, John K Marshall, Vipul Jairath, Stephen B Hanauer, Walter Reinisch, Parambir S Dulai\",\"doi\":\"10.1093/ecco-jcc/jjae092\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>It is unclear if steroid tapering protocols can affect clinical trial outcomes in ulcerative colitis [UC], particularly fixed versus adaptive steroid tapering. Fixed steroid tapering involves incremental dose decreases at prespecified intervals, and adaptive steroid tapering uses investigator discretion as determined by the patient's response.</p><p><strong>Methods: </strong>In this post-hoc analysis from six clinical trials of UC [VARSITY, ACT 1, PURSUIT, GEMINI1, OCTAVE, and ULTRA2], responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for treat-through versus re-randomisation designs, and multivariate regression was performed to account for other potential confounding variables. The primary outcome was corticosteroid-free clinical remission [CR] at 1 year, and secondary outcomes were CR and endoscopic improvement.</p><p><strong>Results: </strong>There was a total of 861 patients who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid tapering regimens were less likely to achieve corticosteroid-free CR at 1 year (odds ratio [OR] 0.66 [95% confidence interval, CI, 0.48-0.92], p = 0.015) but had increased odds for achieving CR at 1 year (OR 1.9 [95% CI 1.43-2.52], p < 0.001). The steroid tapering regimen was not associated with achievement of endoscopic improvement at 1 year.</p><p><strong>Conclusions: </strong>Among patients with UC on corticosteroids in clinical trials, patients using adaptive steroid weaning regimens were less likely to achieve corticosteroid-free CR at 1 year but more likely to achieve CR at 1 year. Consideration should be given to implementing mandatory fixed steroid weaning protocols in future clinical trials of UC.</p>\",\"PeriodicalId\":94074,\"journal\":{\"name\":\"Journal of Crohn's & colitis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532608/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Crohn's & colitis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/ecco-jcc/jjae092\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Crohn's & colitis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/ecco-jcc/jjae092","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
简介:目前尚不清楚类固醇减量方案是否会影响溃疡性结肠炎(UC)的临床试验结果,尤其是固定类固醇减量与适应性类固醇减量。固定类固醇减量包括在预先规定的时间间隔内递增剂量,而适应性类固醇减量则由研究者根据患者的反应酌情决定:在这项对六项 UC 临床试验(VARSITY、ACT 1、PURSUIT、GEMINI1、OCTAVE 和 ULTRA2)进行的事后分析中,基线使用皮质类固醇的诱导治疗应答者被视为主要关注人群。考虑到直通式治疗与再随机化设计,并考虑到其他潜在的混杂变量,进行了调整和多变量回归。主要结果是一年后无皮质类固醇临床缓解(CR),次要结果是CR和内镜改善:结果:共有 861 名患者在诱导治疗后获得了临床应答,并使用了皮质类固醇。在多变量分析中,使用适应性类固醇减量方案的患者在一年后达到无皮质类固醇CR的几率较低(几率比[OR] 0.66 [95% CI 0.48-0.92],P=0.015),但在一年后达到CR的几率增加(OR 1.9 [95% CI 1.43-2.52],P结论:在临床试验中使用皮质类固醇激素的UC患者中,使用适应性类固醇激素断药方案的患者一年后达到无皮质类固醇激素CR的几率较低,但一年后达到CR的几率较高。在未来的 UC 临床试验中,应考虑实施强制性固定类固醇激素断药方案。
Adaptive Steroid Tapering Impedes Corticosteroid-free Remissions Compared with Forced Tapering in Clinical Trials of Ulcerative Colitis.
Introduction: It is unclear if steroid tapering protocols can affect clinical trial outcomes in ulcerative colitis [UC], particularly fixed versus adaptive steroid tapering. Fixed steroid tapering involves incremental dose decreases at prespecified intervals, and adaptive steroid tapering uses investigator discretion as determined by the patient's response.
Methods: In this post-hoc analysis from six clinical trials of UC [VARSITY, ACT 1, PURSUIT, GEMINI1, OCTAVE, and ULTRA2], responders to induction therapy with baseline corticosteroid use were considered as the primary population of interest. Adjustments were made to account for treat-through versus re-randomisation designs, and multivariate regression was performed to account for other potential confounding variables. The primary outcome was corticosteroid-free clinical remission [CR] at 1 year, and secondary outcomes were CR and endoscopic improvement.
Results: There was a total of 861 patients who had achieved clinical response after induction and were using corticosteroids. Within multivariate analysis, patients using adaptive steroid tapering regimens were less likely to achieve corticosteroid-free CR at 1 year (odds ratio [OR] 0.66 [95% confidence interval, CI, 0.48-0.92], p = 0.015) but had increased odds for achieving CR at 1 year (OR 1.9 [95% CI 1.43-2.52], p < 0.001). The steroid tapering regimen was not associated with achievement of endoscopic improvement at 1 year.
Conclusions: Among patients with UC on corticosteroids in clinical trials, patients using adaptive steroid weaning regimens were less likely to achieve corticosteroid-free CR at 1 year but more likely to achieve CR at 1 year. Consideration should be given to implementing mandatory fixed steroid weaning protocols in future clinical trials of UC.