Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat

Tesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy.

1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm², a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin.

Data were analyzed from two Phase 3 studies in which HIV-infected patients with excess abdominal fat were randomized in a 2:1 ratio to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) subcutaneously daily for 6 months, using ANOVA and ANCOVA models.

Metabolic syndrome (MetS-IDF or MetS-NCEP) and FRS were significantly associated with VAT at baseline. Presence of metabolic syndrome ([MetS-NCEP), triglyceride levels >1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively). No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm² for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI) and baseline VAT (95% confidence interval [CI] 2.03; 7.44).

Individuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm² was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo.

Below: Mean change from baseline to 6 months in VAT by treatment and baseline disease-risk category

Baseline risk score (by FRS, MetS-NCEP or MetS-IDF) and the interaction between baseline risk score and treatment showed that the treatment effect of tesamorelin versus placebo was greater in patients with MetS-NCEP compared with those without MetS-NCEP (interaction p = 0.054). Abbreviation: FRS, Framingham Risk Score; MetS-IDF, International Diabetes Foundation definition of metabolic syndrome; MetS-NCEP, National Cholesterol Education Program-defined metabolic syndrome; VAT: visceral adipose tissue.

Full article at: http://goo.gl/8yJ8Pk

By:

Alexandra Mangili, Brooke Hayward

EMD Serono, Inc., Rockland, Massachusetts, United States of America

Julian Falutz

HIV Metabolic Unit, McGill University Health Centre, Montreal, Quebec, Canada

Jean-Claude Mamputu

Theratechnologies Inc., Montreal, Quebec, Canada

Miganush Stepanians

PROMETRIKA, Cambridge, Massachusetts, United States of America

   

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