Evaluation of Potential Continuation Rules for Mepolizumab Treatment of Severe Eosinophilic Asthma

J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):874-882.e4. doi: 10.1016/j.jaip.2017.11.026. Epub 2017 Dec 16.

Abstract

Background: Mepolizumab significantly reduces exacerbations in patients with severe eosinophilic asthma. The early identification of patients likely to receive long-term benefit from treatment could ensure effective resource allocation.

Objective: To assess potential continuation rules for mepolizumab in addition to initiation criteria defined as 2 or more exacerbations in the previous year and blood eosinophil counts of 150 cells/μL or more at initiation or 300 cells/μL or more in the previous year.

Methods: This post hoc analysis included data from 2 randomized, double-blind, placebo-controlled studies (NCT01000506 and NCT01691521) of mepolizumab in patients with severe eosinophilic asthma (N = 1,192). Rules based on blood eosinophils, physician-rated response to treatment, FEV1, Asthma Control Questionnaire (ACQ-5) score, and exacerbation reduction were assessed at week 16. To assess these rules, 2 key metrics accounting for the effects observed in the placebo arm were developed.

Results: Patients not meeting continuation rules based on physician-rated response, FEV1, and the ACQ-5 score still derived long-term benefit from mepolizumab. Nearly all patients failing to reduce blood eosinophils had counts of 150 cells/μL or less at baseline. For exacerbations, assessment after 16 weeks was potentially premature for predicting future exacerbations.

Conclusion: There was no evidence of a reliable physician-rated response, ACQ-5 score, or lung function-based continuation rule. The added value of changes in blood eosinophils at week 16 over baseline was marginal. Initiation criteria for mepolizumab treatment provide the best method for assessing patient benefit from mepolizumab treatment, and treatment continuation should be reviewed on the basis of a predefined reduction in long-term exacerbation frequency and/or oral corticosteroid dose.

Keywords: Anti–IL-5; Continuation; Response; Severe asthma; mAb.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Asthmatic Agents / administration & dosage*
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / physiopathology
  • Double-Blind Method
  • Eosinophilia / drug therapy*
  • Eosinophils / immunology
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Severity of Illness Index

Substances

  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal, Humanized
  • mepolizumab

Associated data

  • ClinicalTrials.gov/NCT01000506
  • ClinicalTrials.gov/NCT01691521