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.

3rd Department of Internal Medicine 1st Medical Faculty Charles University Prague Czech Republic

Aix Marseille UniversitéCNRS CRN2M UMR 7286 Marseille France

APHMHôpital Conception Service d'Endocrinologie Diabète et Maladies Métaboliques Centre de Référence des Maladies Rares d'Origine Hypophysaire Marseille France

Assistance Publique Hôpitaux de ParisHôpitaux Universitaires Paris Sud Hôpital de Bicêtre Service d'Endocrinologie et des Maladies de la Reproduction Le Kremlin Bicêtre France

Clinical NeuroendocrinologyMax Planck Institute of Psychiatry Munich Germany

Department of Biotechnological and Applied Clinical SciencesUniversity of L'Aquila L'Aquila and Neuromed IRCCS Pozzilli Italy

Department of EndocrinologyDiabetes and Metabolism Section and Instituto de Investigação e Inovação em Saúde University of Porto Centro Hospitalar S João Porto Portugal

Department of EndocrinologyDiabetes and Nutrition University Hospital of Reims Reims France

Department of Internal MedicineEndocrinology Section Centre Hospitalier Universitaire de Liège University of Liège Domaine Universitaire du Sart Tilman Liège Belgium

Department of Internal MedicineEndocrinology Section Erasmus University Medical Center Rotterdam The Netherlands

Dipartimento di Medicina Clinica e ChirurgiaUniversità Federico 2 di Napoli Naples Italy

Inserm 1185Fac Med Paris Sud Univ Paris Sud Université Paris Saclay Le Kremlin Bicêtre France

Servicio de EndocrinologíaHospital Universitario La Ribera Valencia Spain

References provided by Crossref.org

Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) Database