Objective: To assess if weekly administration of 40 mg pegvisomant (PEG-V) improves quality of life (QoL) and metabolic parameters in acromegalic patients with already normal age-adjusted insulin-like growth factor-I (IGF-I) concentrations during long-acting somatostatin analog (SSA) treatment.
Design: Prospective investigator-initiated, double blind, placebo controlled, cross-over study. Twenty acromegalic subjects received for two consecutive treatment periods of 16 weeks either PEG-V or placebo, separated by a wash-out period of 4 weeks. Efficacy was assessed as change between baseline and end of each treatment period. QoL was assessed by the Acromegaly Quality of Life Questionnaire (AcroQoL) and the Patient-assessed Acromegaly Symptom Questionnaire (PAQ5).
Results: The AcroQoL (P=0.008) and AcroQol physical (P=0.002) improved significantly after PEG-V was added. The addition of PEG-V also significantly improved the PAQ5 (P=0.038) and the single PAQ5 questions, perspiration (P=0.024), soft tissue swelling (P=0.036) and overall health status (P=0.035). No significant change in Z-score of IGF-I (P=0.34) or the Z-score of serum IGF-I bioactivity (P=0.667) was observed during addition of PEG-V. The improved QoL in the AcroQoL physical was well correlated with weight loss (r=0.46, P=0.04) but not with change in Z-score of (bioactive) IGF-I. Transient liver enzyme disturbances were observed in five subjects (25%) and two patients also suffered from diabetes Mellitus.
Conclusion: Improvement in quality of life was observed without significant change in (the bioactivity of) IGF-I after the addition of 40 mg pegvisomant weekly to monthly long-acting SSA therapy in acromegalic patients who already did normalize in their IGF-I on SSA monotherapy. These data question our current insight in how to assess disease activity. Moreover, it questions the current step-up approach of medical treatment in which pegvisomant only has a role when SSA therapy has failed normalizing IGF-I.
25 - 29 Apr 2009
European Society of Endocrinology