A systematic review and meta-analysis of safety and efficacy parameters of sotatercept in the therapy of pulmonary arterial hypertension.

INTRODUCTION

Pulmonary arterial hypertension (PAH) has responded favorably to the new fusion protein named sotatercept. This study aimed to evaluate the safety and efficacy of sotatercept in PAH.

METHODS

The online databases like PubMed/Medline, Cochrane Library, and ClinicalTrials.gov were searched until 15 September 2024 for studies comparing sotatercept to placebo using keywords such as "sotatercept, pulmonary arterial hypertension, and 'fusion protein.'

RESULTS

Of the 213 titles searched, after removing duplicates, 142 studies were evaluated for eligibility. Two RCTs were finally included. Subgroup analysis was conducted for the two doses (0.7 mg/kg and 0.3 mg/kg). In the safety analysis, there were no significant differences in total adverse events [RR = 1.03 (0.95, 1.12), I2 = 0, p = 0.50], serious adverse events [RR = 0.96 (0.38, 2.42), I2 = 56, p = 0.93], and mortality [RR = 0.39 (0.01, 11.81), I2 = 61%, p = 0.59]. However, a significant difference was observed with non-serious adverse events [RR = 1.15 (1.03-1.30), I2 = 0%, p = 0.02], telangiectasia [RR = 3.34 (1.26-8.83), p = 0.02], thrombocytopenia [RR = 3.69 (1.23-11.0), I2 = 0%, p = 0.02] and epistaxis [RR = 5.58 (2.20-14.13), p = 0.0003]. No significant difference was observed with headache, nasopharyngitis, hypotension, neutropenia, nausea, diarrhea, rash, anemia, and dizziness. A significant change was observed with the majority of efficacy parameters, like Pro BNP [MD = -1150.38 (-1846.44, -454.32), I2 = 79, p = 0.001], pulmonary vascular resistance [MD = -234.40 (-325.30, -143.51), I2 = 72, p < 0.00001], pulmonary arterial wedge pressure (p = 0.007) and improvement in WHO functional class [OR = 3.23 (1.25, 8.34), I2 = 61, p = 0.02].

CONCLUSION

This study demonstrates that sotatercept is more effective than placebo in treating PAH and has a fair safety profile.

CLINICALTRIAL.GOV: Identifier numbers: NCT04576988 and NCT03496207 PROSPERO: CRD42024534695.