Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia.
Clin Gastroenterol Hepatol. 2021 Oct;19(10):2082-2092.e10. doi: 10.1016/j.cgh.2020.08.021. Epub 2020 Aug 12.
BACKGROUND & AIMS: Ustekinumab is a monoclonal antibody against interleukin 12 and interleukin 23 that has been approved by the Food and Drug Administration for treatment of Crohn's disease (CD). We sought to identify the ideal position for ustekinumab in treatment algorithms for CD.
We constructed a Markov model to identify an optimal treatment sequence for CD that included ustekinumab for 1 year or more. The base case was a 35-year old male with moderate to severe CD who had not previously received biologic or immunomodulator therapy. The standard of care treatment algorithm was defined as initial therapy with infliximab and azathioprine, followed by adalimumab and azathioprine, vedolizumab, and lastly surgical resection. The model assessed positions for ustekinumab before standard of care, ustekinumab after infliximab and azathioprine but before the remaining treatments, after infliximab, azathioprine, and adalimumab but before vedolizumab and surgery, or after the other biologics but before surgery. We derived transition probabilities and quality adjusted life years (QALYs) from relevant trials, observational studies, and time trade-off analyses. Primary analyses consisted of first order Monte Carlo simulation of 100 trials of cohorts of 100,000 individuals.
Ustekinumab as first-line therapy yielded the greatest QALYs (incremental effectiveness, 0.016-0.020 QALYs), resulting in 10% more patients in remission or response, and 2% fewer surgeries at 1 year, compared with other algorithms. The model was not sensitive to 25% variation in transition probabilities.
In a simulation based on a 35-year old male patient with moderate to severe CD, we found that ustekinumab as the first-line biologic therapy yields greater QALYs at the end of 1 year than compared with use later in the CD treatment algorithm.
乌司奴单抗是一种针对白细胞介素 12 和白细胞介素 23 的单克隆抗体，已被美国食品和药物管理局批准用于治疗克罗恩病（CD）。我们旨在确定乌司奴单抗在 CD 治疗方案中的理想位置。
我们构建了一个马尔可夫模型，以确定一种包含乌司奴单抗治疗 1 年或更长时间的最优 CD 治疗方案。基本情况是一位 35 岁的男性，患有中重度 CD，之前未接受过生物制剂或免疫调节剂治疗。标准治疗方案被定义为初始治疗使用英夫利昔单抗和硫唑嘌呤，然后使用阿达木单抗和硫唑嘌呤、维得利珠单抗，最后是手术切除。该模型评估了乌司奴单抗在标准治疗之前、英夫利昔单抗和硫唑嘌呤之后但在其余治疗之前、英夫利昔单抗、硫唑嘌呤和阿达木单抗之后但在维得利珠单抗和手术之前、或在其他生物制剂之后但在手术之前的位置。我们从相关试验、观察性研究和时间权衡分析中得出转移概率和质量调整生命年（QALY）。主要分析包括对 100 个队列（每个队列 10 万人）进行一阶蒙特卡罗模拟。
乌司奴单抗作为一线治疗可获得最大的 QALY（增量效果为 0.016-0.020 QALY），与其他方案相比，1 年内缓解或应答的患者比例增加 10%，手术比例减少 2%。模型对转移概率 25%的变化不敏感。
在基于一位 35 岁中重度 CD 男性患者的模拟中，我们发现乌司奴单抗作为一线生物治疗药物在 1 年末比在 CD 治疗方案中较晚使用可获得更多的 QALY。
