Comparative Effectiveness of Sotatercept and Approved Add-On Pulmonary Arterial Hypertension Therapies: A Systematic Review and Network Meta-Analysis.

Abstract

There are no direct comparisons of sotatercept to add-on therapies approved for 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, the Cochrane CENTRAL, and Clinicaltrials.gov until April 15, 2023, for randomized trials involving PAH patients treated with add-on sotatercept or add-on other PAH therapies. Data extraction and risk of bias assessments were performed independently and in duplicate using the Cochrane RoB 2.0 tool. We performed frequentist random-effects network meta-analysis using the restricted maximum likelihood (REML) estimator and assessed the certainty of evidence using the GRADE approach. Our search found 18 trials (5777 patients) eligible for analysis. Sotatercept reduces clinical worsening as compared to placebo (RR 0.21 [95% CI 0.11 to 0.41]; high certainty). Sotatercept probably reduces clinical worsening more compared to add-on ERA (RR 0.28 [95% CI 0.14 to 0.55]), prostanoid (Inh) (RR 0.21 [95% CI 0.07 to 0.67]), and prostanoid (PO) (RR 0.32 [95% CI 0.16 to 0.67]) (all moderate certainty). Sotatercept probably improves 6MWD as compared to placebo (MD 36.89m [95% CI 25.26 to 48.51]). Although sotatercept probably improves 6MWD more than add-on ERA (MD 18.38m [95% CI 5.92 to 30.84]) and prostanoid (PO) (MD 25.66m [95% CI 13.71 to 37.61]), it did not exceed the MCID of 33m (both moderate certainty). Sotatercept is an effective add-on therapy for PAH, likely superior to many approved add-on PAH therapies in reducing clinical worsening.