More than a decade of real-world experience of pegvisomant for acromegaly: ACROSTUDY.

Objective To report the final long-term safety and efficacy analyses of patients with acromegaly treated with pegvisomant from the ACROSTUDY. Design Global (15 countries), multicentre, non-interventional study (2004-2017). Methods The complete ACROSTUDY cohort comprised patients with acromegaly, who were being treated with pegvisomant (PEGV) prior to the study or at enrolment. Main endpoints were long-term safety (comorbidities, adverse events [AEs], pituitary tumour volumes, liver tests) and efficacy (IGF-1 changes). Results Patients (n = 2221) were treated with PEGV for a median of 9.3 years (range, 0-20.8 years) and followed up for a median of 7.4 years (range, 0-13.9 years). Before PEGV, 96.3% had received other acromegaly treatments (surgery/radiotherapy/medications). Before PEGV treatment, 87.2% of patients reported comorbidities. During ACROSTUDY, 5567 AEs were reported in 56.5% of patients and of these 613 were considered treatment-related (in 16.5% of patients) and led to drug withdrawal in 1.3%. Pituitary imaging showed a tumour size increase in 7.1% of patients; the majority (71.1%) reported no changes. Abnormal AST or ALT liver tests occurred in 3.2% of patients. IGF-1 normalization rate improved over time, increasing from 11.4% at PEGV start to 53.7% at year 1, and reaching 75.4% at year 10 with use of ≥30 mg PEGV/day in an increasing proportion of patients. Conclusion This comprehensive review of the complete cohort in ACROSTUDY confirmed the overall favourable benefit-to-risk profile and high efficacy of PEGV as mono- and combination therapy in patients with an aggressive course/uncontrolled/active acromegaly requiring long-term medical therapy for control.