Endocrine Abstracts (2008) 15 P238

Successful use of once weekly pegvisomant administration in patients with acromegaly

Claire Higham1, Julia Thomas2, Will M Drake2 & Peter Trainer1

1Christie Hospital, Manchester, UK; 2St Bartholomew’s Hospital, London, UK.

Initial clinical trials with pegvisomant at doses of up to 80 mg once weekly led to a 30% fall in IGF-I. Subsequently, daily administration of up to 40 mg/day (280 mg/week) achieved an IGF-I within reference range in 97% of patients. Pegvisomant’s half-life is >70 h suggesting weekly dosing may be possible using higher doses than in the original trials.

We performed a two-centre, open-label prospective study in seven patients (4M, 3F, mean age 57 years, 6/7 prior trans-sphenoidal surgery, 7/7 prior radiotherapy) with acromegaly taking pegvisomant (median dose 10 mg daily (range 10–20 mg od), IGF-I normal for 3 months on stable dose). Patients were converted from daily pegvisomant dosing, initially to twice weekly (week 0–16) followed by once weekly (week 16–32) administration, with total weekly dose remaining the same. IGF-I (Immulite-2000, Siemens) was measured at 6, 14, 24 and 32 weeks, with dose adjustments of pegvisomant if required. Safety, metabolic and QOL parameters were monitored at each visit.

Six patients completed the twice weekly and five patients the once weekly administration. Headaches led to 2 patient withdrawals at 0+24 weeks. Mean pre-dose IGF-I levels remained stable with the different administration regimens (table, one way RM-ANOVA P=0.6) and all values were within age adjusted IGF-I reference range. We were able to reduce pegvisomant dose from 105 to 90 mg per week in one patient and five patients opted to continue weekly administration at trial termination. Safety, metabolic and QOL parameters remained stable (Table).

Parameter (mean±S.D.)BaselineTwice weeklyOnce weekly
IGF-I (ng/ml)145±39124±39127±22
Weight (kg)82±1181±1183±6
ALT (IU/l)29±1125±629±11
Fasting glucose (mmol/l)4.6±0.45.7±1.64.7±0.4

To conclude, twice and once weekly administration of pegvisomant is effective in controlling IGF-I levels in acromegaly and overall patients preferred the weekly dosing interval.

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