Pneumologie 2017; 71(S 01): S1-S125
DOI: 10.1055/s-0037-1598375
Posterbegehung – Sektion Klinische Pneumologie
Asthma bronchiale – Stephanie Korn/Mainz, Christian Geßner/Leipzig
Georg Thieme Verlag KG Stuttgart · New York

ENCORE: A weight-based exacerbation dose response analysis of mepolizumab in severe asthma with eosinophilic phenotype

I Pouliquen
1  Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park
D Austin
1  Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park
N Gunsoy
2  Clinical Statistics, GlaxoSmithKline, Stockley Park
SW Yancey
3  Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park
› Author Affiliations
Further Information

Publication History

Publication Date:
23 February 2017 (online)



Despite careful design of dose ranging studies, full characterisation of dose response for clinical endpoints is not always achieved. The absence of a dose response for reduction in clinically significant exacerbations with mepolizumab in the primary analysis led to a meta-analysis using individualized weight-based measures of dose to take advantage of the known effect of bodyweight on mepolizumab exposure.


Evaluate weight-based measures of mepolizumab dose-response for reduction in annualized exacerbation rate.


Inclusion of exacerbation data with dose and bodyweight information from two GSK funded mepolizumab severe asthma pivotal studies (DREAM, NCT01000506 and MENSA, NCT01000506). Intravenous doses were converted to subcutaneous-equivalent dose using absolute bioavailability of 80 and 70% and normalized by individual body weight, body mass index and body surface area at baseline.


Description of the dose response showed that although the maximal treatment effect was well-estimated, location of half-maximal efficacious dose (ED50) was poor. Using a Bayesian analysis with informative priors for ED50 (away from the pharmacological ED50 (blood eosinophil reduction) [11 mg]), convergence was achieved. Posterior ED50 distributions showed a shift in prior belief towards the pharmacological ED50 with narrower credibility interval. The largest effects were noted for bodyweight-adjusted dose response.


Exacerbation data from studies DREAM and MENSA did not show a dose response by conventional analysis unlike with Bayesian analysis which also showed consistency between the efficacy dose response and the well-defined dose response for pharmacology, with an ED50 of approximately 0.17 mg/kg or 12 mg.

Abstract previously presented at ERS 2016, PA4106