Successful use of weekly pegvisomant administration in patients with acromegaly.

Abstract

Context Clinical trials using 80 mg once-weekly pegvisomant in active acromegaly led to a 30% fall in serum IGF-I. Subsequent studies demonstrated that daily administration of up to 40 mg/day achieved an IGF-I within reference range in 97% of patients. Pegvisomant has a half-life of >70hrs suggesting weekly dosing may be possible but using higher doses than in the initial trials. Objective To determine the efficacy of weekly dosing of pegvisomant. Design A two-center, open-label prospective study in patients with acromegaly converted from a stable daily dose of pegvisomant (median dose 15 mg daily [range 10-20 mg od], IGF-I normal for 3 months prior to inclusion) to twice-weekly (week 0-16) followed by once-weekly (week 16-32) administration. Results Seven patients (4M, age 57+/-7 yrs, 6/7 prior trans-sphenoidal surgery, 7/7 prior radiotherapy) were recruited. Six patients completed the twice-weekly and five patients both the twice-weekly and once-weekly administration. Headaches led to 2 patient withdrawals at 0 + 24 weeks. Mean pre-dose serum IGF-I levels remained stable with the different administration regimens (IGF-I baseline 145+/-39 ng/ml, twice-weekly 124+/-39 ng/ml and once-weekly 127+/-22 ng/ml) and all values were within age adjusted IGF-I reference range. Pegvisomant dose was reduced in 2 patients and 5 opted to continue weekly administration at trial termination. Safety and QOL parameters remained stable. Conclusions Twice and once-weekly administration of pegvisomant is effective in controlling serum IGF-I levels in acromegaly and although not formally assessed, continuation of weekly dosing in 5 patients at study conclusion suggests patient preference for this regimen.