Long-term safety and efficacy of pegvisomant monotherapy for acromegaly: final data from the full ACROSTUDY cohort

Purpose: ACROSTUDY was an international, non-interventional, cross-sectional study that evaluated the long-term safety and treatment outcomes of pegvisomant treatment (monotherapy or combination) in patients with acromegaly in “real-world” clinical practice. This study aimed to characterize the long-term safety and efficacy of pegvisomant monotherapy in ACROSTUDY. Methods: Patients with acromegaly aged > 18 years (at ACROSTUDY enrollment) who had received ≥ 1 dose of pegvisomant as monotherapy were included in the monotherapy cohort. Clinical assessments included adverse events (AEs), comorbidities, pituitary imaging, liver function tests, and insulin-like growth factor-1 (IGF-I) serum measurements. Results: Patients with acromegaly (N = 1464) received pegvisomant monotherapy for a median (min, max) of 6.0 (0.0, 19.3) years and were followed in ACROSTUDY for a mean of 7.6 years. The rates of AEs (all-causality) and serious AEs were 49% (n = 717/1464) and 19.3% (n = 282/1464), respectively. The most common treatment-related AEs were IGF-I increased (1.8%), lipohypertrophy (1.2%), transaminases increased (1.2%), and IGF-I decreased (1.1%). There were 31 (2.1%) deaths and none were related to treatment. Magnetic resonance imaging findings at study sites showed 7.2% (n = 90/1248) of patients had increased tumor size, whereas 70.6% (n = 881/1248) of patients had change in tumor size. At the last observation, the serum IGF-I normalization rate was 62.3% (n = 756/1213) and the median (min, max) daily pegvisomant dose was 15.0 (0, 60) mg/day. Conclusions: In this largest and longest real-world study of pegvisomant monotherapy in patients with acromegaly to date, pegvisomant demonstrated a favorable safety profile and was effective at normalizing and maintaining IGF-I levels in the majority of patients.