SAT-428 Effect of Age, Body Mass Index, and Sex on the Performance of Macimorelin for the Diagnosis of Adult Growth Hormone Deficiency: A Post Hoc Analysis

Abstract

Background: The diagnostic performance of macimorelin (MAC), an orally active ghrelin receptor agonist approved for the diagnosis of adult growth hormone deficiency (AGHD) in the United States, has previously been demonstrated in a phase 3 study that compared MAC with the insulin tolerance test (ITT).1 However, it is not known if the diagnostic performance of MAC varies according to patient demographics that are known to influence peak growth hormone release induced by other secretagogues. Objective: To determine whether the performance of the MAC diagnostic test is affected by age, baseline body mass index (BMI), and sex. Methods: This post hoc analysis included data from a previously published phase 3 study of subjects with a high likelihood of GHD (Group A, considered to have AGHD based on having a low IGF-I level plus either of these: at least 3 other pituitary hormone deficiencies or a structural hypothalamic or pituitary lesion) vs healthy controls (Group D).1 The probability of AGHD was estimated using 4 logistic models fitted to the data: unadjusted, age-adjusted, baseline BMI-adjusted, and sex-adjusted. Each model considers all subjects as independent observations, not taking matching into account. The area under the curve (AUC) of the estimated receiver operating characteristic (ROC) curve (0 to 1 range, where 1 is perfect) from each adjusted model was compared with the AUC from the unadjusted model. The estimated sensitivity and specificity for each model at cutpoint values of 2.8 and 5.1 ng/mL were calculated. Results: Of the 70 subjects included in the analysis, 41 had a high likelihood of GHD and 29 were healthy controls; mean±SD (range) age was 41.7±13.9 (18-66) years, mean±SD (range) BMI was 27.1±4.0 (20.8-36.6) kg/m2, and 56% were male. The ROC AUC for the unadjusted model was 0.9924 (95% CI: 0.9807, 1), age-adjusted ROC AUC was 0.9924 (95% CI: 0.9807, 1), BMI-adjusted ROC AUC was 0.9916 (95% CI: 0.9786, 1), and sex-adjusted ROC AUC was 0.9950 (95% CI: 0.9861, 1). For the unadjusted model at cutpoint values of 2.8 and 5.1, estimated sensitivity was 88% and 93%, and specificity was 97% and 97%. These values remained the same for cutpoint 2.8 when adjusting for age and adjusting for mean or median BMI. At cutpoint 5.1, the values remained the same when adjusting for age and mean BMI. When adjusting for sex, sensitivity for females was 88% and specificity was 93% at cutpoint 2.8, and sensitivity for females was 94% and specificity was 93% at cutpoint 5.1. Sensitivity for males was 88% and specificity was 100% at cutpoint 2.8, and sensitivity for males was 92% and specificity was 100% at cutpoint 5.1. Conclusions: Results of this post hoc analysis show that the diagnostic performance of MAC was not meaningfully affected by age, baseline BMI, or sex over the ranges that were studied. Reference: 1. Garcia JM, et al. J Clin Endocrinol Metab. 2018;103(8):3083-3093.