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Gender, Body Weight, Disease Activity, and Previous Radiotherapy Influence the Response to Pegvisomant

Department of Diabetes and Endocrinology (C.P.), Ipswich Hospital, Ipswich IP4 5PD, United Kingdom; Department of Endocrinology (P.B.), University Hospital MAS, Malmö S-205 02, Sweden; Pfizer Inc. (M.M.), New York, New York 10017; and Department of Endocrinology (P.J.T.), Christie Hospital, Manchester M20 4BX, United Kindgom

Address all correspondence and requests for reprints to: Dr. Craig Parkinson, Department of Diabetes and Endocrinology, The Ipswich Hospital National Health Service Trust, Heath Road, Ipswich, Suffolk IP4 5PD, United Kingdom. E-mail: Craig.Parkinson{at}ipswichhospital.nhs.uk.

Context/Objective: To effectively normalize IGF-I in patients with acromegaly, various covariates may affect dosing and plasma concentrations of pegvisomant. We assessed whether sex, age, weight, and previous radiotherapy influence dosing of pegvisomant in patients with active disease.

Design: Data from 69 men and 49 women participating in multicenter, open-label trials of pegvisomant were retrospectively evaluated using multiple regression techniques. Sixty-nine subjects (39 men, 30 women) had undergone external beam pituitary radiotherapy. Serum IGF-I was at least 30% above age-related upper limit of normal in all patients at study entry. After a loading dose of pegvisomant (80 mg), patients were commenced on 10 mg/d. Pegvisomant dose was adjusted by 5 mg every eighth week until serum IGF-I was normalized.

Results: At baseline, men had significantly higher mean serum IGF-I levels than women despite similar GH levels. After treatment with pegvisomant, IGF-I levels were similar in men and women. A significant correlation between baseline GH, IGF-I, body weight, and the dose of pegvisomant required to normalize serum IGF-I was observed (all P < 0.001). Women required an average of 0.04 mg/kg more pegvisomant than men and a mean weight-corrected dose of 19.2 mg/d to normalize serum IGF-I [14.5 mg/d (men); P < 0.001]. Patients treated with radiotherapy required less pegvisomant to normalize serum IGF-I despite similar baseline GH/IGF-I levels (15.2 vs. 18.5 mg/d for no previous radiotherapy; P = 0.002).

Conclusions: Sex, body weight, previous radiotherapy, and baseline GH/IGF-I influence the dose of pegvisomant required to normalize serum IGF-I in patients with active acromegaly.

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