A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues.

Abstract:

BACKGROUND:Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients, and various covariates may affect its dosing and pharmacokinetics. OBJECTIVE:To identify predictors of the PEGV dose required to normalize insulin-like growth factor I (IGF-I) levels during PEGV monotherapy and in combination with long-acting somatostatin analogues (LA-SSAs). DESIGN:Two retrospective cohorts (Rotterdam + Liège Acromegaly Survey (LAS), total n = 188) were meta-analyzed as a form of external replication to study the predictors of PEGV dosing in addition to LA-SSA, the LAS (n = 83) was used to study the predictors of PEGV monotherapy dosing. Multivariable regression models were used to identify predictors of the PEGV dose required to normalize IGF-I levels. RESULTS:For PEGV dosing in combination with LA-SSA, IGF-I levels, weight, height and age, were associated with the PEGV normalization dosage (P ≤ 0.001, P ≤ 0.001, P = 0.028 and P = 0.047 respectively). Taken together, these characteristics predicted the PEGV normalization dose correctly in 63.3% of all patients within a range of ±60 mg/week (21.3% within a range of ±20 mg/week). For monotherapy, only weight was associated with the PEGV normalization dose (P ≤ 0.001) and predicted this dosage correctly in 77.1% of all patients within a range of ±60 mg/week (31.3% within a range of ±20 mg/week). CONCLUSION:In this study, we show that IGF-I levels, weight, height and age can contribute to define the optimal PEGV dose to normalize IGF-I levels in addition to LA-SSA. For PEGV monotherapy, only the patient's weight was associated with the IGF-I normalization PEGV dosage.

journal_name

Eur J Endocrinol

authors

Franck SE,Korevaar TIM,Petrossians P,Daly AF,Chanson P,Jaffrain-Réa ML,Brue T,Stalla GK,Carvalho D,Colao A,Hána V,Delemer B,Fajardo C,van der Lely AJ,Beckers A,Neggers SJCMM

doi

10.1530/EJE-16-0956

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

421-431

issue

4

eissn

0804-4643

issn

1479-683X

pii

EJE160956

journal_volume

176

pub_type

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