Division of Respirology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Michael G. DeGroote School of Medicine.
Ann Am Thorac Soc. 2024 Aug;21(8):1194-1203. doi: 10.1513/AnnalsATS.202311-942OC.
There are no direct comparisons of sotatercept to add-on therapies approved for pulmonary arterial hypertension (PAH). This study aimed to compare the efficacy and safety of add-on sotatercept versus other add-on therapies using a network meta-analysis. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov until April 15, 2023, for randomized trials involving patients with PAH who were treated with add-on sotatercept or other add-on PAH therapies. Data extraction and risk-of-bias assessments were performed independently and in duplicate using the Cochrane RoB 2.0 tool. We performed a frequentist random-effects network meta-analysis using the restricted maximum-likelihood estimator and assessed the certainty of evidence using the GRADE (grading of recommendations assessment development, and evaluation) approach. Our search found 18 trials (5,777 patients) eligible for analysis. Sotatercept reduces clinical worsening as compared with placebo (relative risk [RR], 0.21; 95% confidence interval [CI] = 0.11-0.41; with high certainty). Sotatercept probably reduces clinical worsening more, compared with add-on endothelin receptor antagonists (RR, 0.28; 95% CI = 0.14-0.55), inhaled prostanoid (RR, 40.21; 95% CI = 0.07-0.67), and prostanoid taken orally (RR, 0.32; 95% CI = 0.16-0.67; all with moderate certainty). Sotatercept probably improves 6-minute-walk distance compared with placebo (mean difference [MD], 36.89 m; 95% CI = 25.26-48.51). Although sotatercept probably improves 6-minute-walk distance more than add-on endothelin receptor antagonists (MD, 18.38 m; 95% CI = 5.92-30.84) and prostanoid taken orally (MD, 25.66 m; 95% CI = 13.71-37.61), it did not exceed the minimal clinically important difference of 33 m (both with moderate certainty). Sotatercept is an effective add-on therapy for PAH, likely superior to many approved add-on PAH therapies in reducing clinical worsening.
目前尚无索他拉特塞与已获批用于肺动脉高压（PAH）的附加疗法直接比较的研究。本研究旨在通过网络荟萃分析比较添加索他拉特塞与其他附加 PAH 疗法的疗效和安全性。我们检索了 MEDLINE、Embase、Cochrane 对照试验中心注册库和 clinicaltrials.gov，以获取截至 2023 年 4 月 15 日的关于接受附加索他拉特塞或其他附加 PAH 疗法治疗的 PAH 患者的随机试验。数据提取和偏倚风险评估由两名独立人员使用 Cochrane RoB 2.0 工具进行。我们使用限制性极大似然估计进行了频率派随机效应网络荟萃分析，并使用 GRADE（推荐评估、制定与评价）方法评估证据确定性。我们的检索发现有 18 项试验（5777 例患者）符合分析条件。与安慰剂相比，索他拉特塞可降低临床恶化风险（相对风险 [RR]，0.21；95%置信区间 [CI] = 0.11-0.41；证据确定性为高）。与附加内皮素受体拮抗剂（RR，0.28；95% CI = 0.14-0.55）、吸入前列环素（RR，40.21；95% CI = 0.07-0.67）和口服前列环素（RR，0.32；95% CI = 0.16-0.67）相比，索他拉特塞可能更能降低临床恶化风险（均为中等确定性）。与安慰剂相比，索他拉特塞可能提高 6 分钟步行距离（平均差值 [MD]，36.89 m；95% CI = 25.26-48.51）。虽然与附加内皮素受体拮抗剂（MD，18.38 m；95% CI = 5.92-30.84）和口服前列环素（MD，25.66 m；95% CI = 13.71-37.61）相比，索他拉特塞可能更能提高 6 分钟步行距离（均为中等确定性），但未超过 33 m 的最小临床重要差值（均为中等确定性）。索他拉特塞是一种有效的 PAH 附加疗法，可能优于许多已获批的附加 PAH 疗法，降低临床恶化风险。
