Wu Guozhi, Yang Yuan, Liu Min, Wang Yuping, Guo Qinghong
The First Clinical Medical College, Lanzhou University, Lanzhou, China.
Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.
Front Pharmacol. 2021 Apr 14;12:655865. doi: 10.3389/fphar.2021.655865. eCollection 2021.
Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials. To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD. We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807. Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35-4.97; OR 2.96, 95% CI 1.57-5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27-5.97; OR 3.10, 95% CI 1.47-6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31-7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85-34.77), adalimumab (OR 10.76, 95% CI 2.61-52.35), certolizumab pegol (OR 4.41, 95% CI 1.10-21.08), vedolizumab (OR 4.99, 95% CI 1.19-25.54) and CT-P13 (OR 10.93, 95% CI 2.10-64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49-10.23), adalimumab (OR 4.86, 95% CI 1.43-16.95), vedolizumab (OR 2.48, 95% CI 1.21-6.52) and CT-P13 (OR 5.15, 95% CI 1.05-27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission. CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.
克罗恩病（CD）是一种影响生活质量的慢性炎症性疾病。有几种药物可用于治疗CD，但由于缺乏高质量的直接比较的随机对照试验，它们的相对疗效尚不清楚。为了对生物类似药、生物制剂和JAK1抑制剂治疗CD的疗效和安全性进行混合比较。我们检索了截至2020年12月28日的PubMed、科学网、Embase和考克兰图书馆，以查找随机对照试验（RCT）。比较分析仅纳入了将生物类似药、生物制剂和JAK1抑制剂与安慰剂或另一种治疗CD的活性药物的疗效或安全性进行比较的RCT。疗效指标为诱导缓解、维持缓解和无类固醇缓解，安全性指标为严重不良事件（AE）和感染。采用贝叶斯方法比较各种治疗方法。注册号为CRD42020187807。在我们的系统评价中确定了28项研究和29项RCT。网络荟萃分析表明，英夫利昔单抗和阿达木单抗优于赛妥珠单抗（OR分别为2.44，95%CI 1.35 - 4.97；OR为2.96，95%CI 1.57 - 5.40）和托法替布（OR分别为2.55，95%CI 1.27 - 5.97；OR为3.10，95%CI 1.47 - 6.52），并且显示CT-P13在诱导缓解方面优于安慰剂（OR为2.90，95%CI 1.31 - 7.59）。英夫利昔单抗（OR为7.49，95%CI 1.85 - 34.77）、阿达木单抗（OR为10.76，95%CI 2.61 - 52.35）、赛妥珠单抗（OR为4.41，95%CI 1.10 - 21.08）、维多珠单抗（OR为4.99，95%CI 1.19 - 25.54）和CT-P13（OR为10.93，95%CI 2.10 - 64.37）在维持缓解方面优于非戈替尼。此外，英夫利昔单抗（OR为3.80，95%CI 1.49 - 10.23）、阿达木单抗（OR为4.86，95%CI 1.43 - 16.95）、维多珠单抗（OR为2.48，95%CI 1.21 - 6.52）和CT-P13（OR为5.15，95%CI 1.05 - 27.58）在无类固醇缓解方面优于安慰剂。在所有治疗方法中，阿达木单抗在诱导缓解方面排名最高，CT-P13在维持缓解和无类固醇缓解方面排名最高。CT-P13比许多生物制剂和JAK1抑制剂更有效，应推荐用于治疗CD。有必要进行进一步的直接比较RCT来比较这些药物。
