Observed Weight Gain in Patients With Pulmonary Arterial Hypertension Treated With Sotatercept.

Sotatercept, an activin signaling inhibitor for pulmonary arterial hypertension (PAH), has demonstrated significant improvements in clinical outcomes though its off-target effects are still an area for discovery. Anecdotal increases in total body weight not attributable to fluid retention have been observed. Understanding the potential for weight gain and body composition changes is important as excessive weight gain in the PAH population is deleterious whereas increases in lean body mass may favorably affect exercise capacity. Therefore, we conducted a single-center retrospective observational cohort study of adult Group 1 PAH patients seen at a Pulmonary Hypertension Association-accredited Comprehensive Care Center treated with sotatercept for a minimum of 12 weeks. The primary endpoint was the proportion of patients who experienced clinically significant weight gain of ≥ 5% with sotatercept treatment. Secondary endpoints were the frequency of sotatercept dose adjustments required due to changes in body weight. Exploratory analyses were conducted to identify potential relationships between weight change and covariates of interest. Of 23 patients included, clinically significant weight gain was observed in 43.5% (n = 10). The median absolute change from baseline weight was 3.18 kg (Q1-Q3, -0.80-7.43 kg), and the median percent change was 4.43 (Q1-Q3, -0.78-9.01). Dosage adjustments based on dosing weight changes (increase or decrease) occurred at an incidence of 1.56 per patient-year. These results suggest the importance of ongoing monitoring of body weight throughout sotatercept treatment and that weight gain is commonly associated with treatment, although not previously observed or evaluated in clinical trials to date.