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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)421-431
Number of pages11
JournalEuropean Journal of Endocrinology
Volume176
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

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Somatostatin
Insulin-Like Growth Factor I
Acromegaly
Weights and Measures
pegvisomant
Somatotropin Receptors
Hormone Antagonists
Pharmacokinetics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Franck, S. E., Korevaar, T. I. M., Petrossians, P., Daly, A. F., Chanson, P., Jaffrain-Rea, M. L., ... Neggers, S. J. C. M. M. (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. https://doi.org/10.1530/EJE-16-0956

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.; Hána, V.; Delemer, B.; Fajardo, C.; Van Der Lely, A. J.; Beckers, A.; Neggers, S. J.C.M.M.

In: European Journal of Endocrinology, Vol. 176, No. 4, 01.04.2017, p. 421-431.

Research output: Contribution to journalArticle

Franck, SE, Korevaar, TIM, Petrossians, P, Daly, AF, Chanson, P, Jaffrain-Rea, ML, Brue, T, Stalla, GK, Carvalho, D, Colao, A, Hána, V, Delemer, B, Fajardo, C, Van Der Lely, AJ, Beckers, A & Neggers, SJCMM 2017, 'A multivariable prediction model for pegvisomant dosing: Monotherapy and in combination with long-acting somatostatin analogues', European Journal of Endocrinology, vol. 176, no. 4, pp. 421-431. https://doi.org/10.1530/EJE-16-0956
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. ; Hána, V. ; Delemer, B. ; Fajardo, C. ; Van Der Lely, A. J. ; Beckers, A. ; Neggers, S. J.C.M.M. / A multivariable prediction model for pegvisomant dosing : Monotherapy and in combination with long-acting somatostatin analogues. In: European Journal of Endocrinology. 2017 ; Vol. 176, No. 4. pp. 421-431.
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AU - Korevaar, T. I.M.

AU - Petrossians, P.

AU - Daly, A. F.

AU - Chanson, P.

AU - Jaffrain-Rea, Marie Lise

AU - Brue, T.

AU - Stalla, G. K.

AU - Carvalho, D.

AU - Colao, A.

AU - Hána, V.

AU - Delemer, B.

AU - Fajardo, C.

AU - Van Der Lely, A. J.

AU - Beckers, A.

AU - Neggers, S. J.C.M.M.

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N2 - 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.

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