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

Franck, S. E.; Korevaar, T. I. M.; Petrossians, P.; Daly, A. F.; Chanson, P.; Jaffrain-Rea, Marie-Lise; Brue, T.; Stalla, G. K.; Carvalho, D.; Colao, A.; Hana Jr., V.; Delemer, B.; Fajardo, C.; van der Lely, A. J.; Beckers, A.; Neggers, S. J. C. M. M.

doi:10.1530/EJE-16-0956

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

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Stalla, G. K.
Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/28100630
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Citation

Franck, S. E., Korevaar, T. I. M., Petrossians, P., Daly, A. F., Chanson, P., Jaffrain-Rea, M.-L., et al. (2017). A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues. EUROPEAN JOURNAL OF ENDOCRINOLOGY, 176(4), 421-431. doi:10.1530/EJE-16-0956.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-868B-3

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 + Lisge 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.