Clinical Research Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
School of Pharmacy, Capital Medical University, Beijing, China.
Front Immunol. 2022 Mar 17;13:828219. doi: 10.3389/fimmu.2022.828219. eCollection 2022.
Information on comparative drug efficacy is of great importance for drug development as well as clinical practice. Up to now, the relative efficacy of biologics and small targeted molecules for Crohn's disease (CD) remains unclear. The objective of this study was to quantify the relative efficacy of investigational and approved biological treatments for CD measured in Crohn's Disease Activity Index (CDAI), Inflammatory Bowel Disease Questionnaire (IBDQ), and C-reactive protein (CRP). The analysis dataset was composed of summary-level data from 46 trials, containing 12,846 patients, with treatment of 24 drugs. Six mathematical models with non-parametric placebo estimations were developed to describe the time course and dose-response of six efficacy measures. The effects of covariate were further evaluated. Time-response relationships were found in outcomes measured in CDAI. The patients' age, disease duration, baseline CDAI, and CRP showed an impact on the efficacy. Model simulations were performed to compare the efficacies across different drugs. The most achievement in clinical remission (defined as CDAI less than 150) and clinical response (defined as the reduction in CDAI for 100 or 70) was observed in the simulation for PF-04236921 and infliximab, respectively. The most improvement in IBDQ was shown in tofacitinib. In general, tumor necrosis factor (TNF)-α inhibitors were the most effective biologics, and the highest efficacy of small targeted molecules was observed in janus kinase (JAK) inhibitors. These findings have important implications for clinical practice in CD.
药物疗效信息对于药物开发和临床实践都非常重要。迄今为止，生物制剂和小分子靶向药物治疗克罗恩病（CD）的相对疗效仍不清楚。本研究的目的是量化 CDAI、IBDQ 和 CRP 评估的研究性和已批准的生物治疗 CD 的相对疗效。分析数据集由来自 46 项试验的汇总数据组成，包含 12846 名患者，接受 24 种药物治疗。开发了 6 种具有非参数安慰剂估计的数学模型来描述 6 种疗效指标的时间过程和剂量反应。进一步评估了协变量的影响。在 CDAI 中测量的结局中发现了时间反应关系。患者年龄、疾病持续时间、基线 CDAI 和 CRP 对疗效有影响。进行了模型模拟以比较不同药物的疗效。在 PF-04236921 和英夫利昔单抗的模拟中，分别观察到临床缓解（定义为 CDAI 小于 150）和临床反应（定义为 CDAI 降低 100 或 70）的最佳疗效。托法替尼在 IBDQ 方面的改善最大。一般来说，肿瘤坏死因子（TNF）-α 抑制剂是最有效的生物制剂，而小分子靶向药物的最高疗效是在 Janus 激酶（JAK）抑制剂中观察到的。这些发现对 CD 的临床实践具有重要意义。
