Response to Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma and Atopic Phenotypes

Abstract

Purpose

Improved understanding of characteristics that may influence treatment response across phenotypes may help guide treatment decisions.

Patients and Methods

This was a post hoc analysis of MENSA, a multicenter, randomized, double-blind, placebo-controlled trial (NCT01691521). Patients aged ≥12 years with severe eosinophilic asthma received mepolizumab (75 mg intravenously or 100 mg subcutaneously) or placebo, plus standard of care, every 4 weeks for 32 weeks. Outcomes assessed were the annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ)-5 score. Subgroup analyses were performed by baseline blood eosinophil count (<150, ≥150–300, ≥300 cells/μL) within atopic subgroups (non-atopic [specific immunoglobulin E <0.35 kU/L], atopic [≥0.35–17.5 kU/L], strongly atopic [>17.5 kU/L]), and by house dust mite (HDM) sensitivity.

Results

Of 576 patients analyzed, 272 were non-atopic, 181 were atopic and 94 were strongly atopic; 29 had missing atopy data. In patients with blood eosinophil counts ≥300 cells/µL, mepolizumab versus placebo reduced clinically significant exacerbations by 74%, 43% and 25% in the non-atopic, atopic and strongly atopic subgroups. Similar reductions were observed in all atopic subgroups in other blood eosinophil count categories where there were sufficient patient numbers for analysis, except for non-atopic patients with baseline blood eosinophil counts of <150 cells/μL. Improvements in ACQ-5 scores of –0.75, –0.73 and –0.78 with mepolizumab versus placebo were observed in non-atopic, atopic and strongly atopic patients with blood eosinophil counts ≥300 cells/µL; consistent improvements in ACQ-5 were not observed in patients with blood eosinophil counts <150 or ≥150–300 cells/μL. Reductions in clinically significant exacerbations with mepolizumab versus placebo were also observed irrespective of sensitivity to HDMs.

Conclusion

Mepolizumab was associated with a trend for reductions in clinically significant exacerbations and improved asthma control versus placebo in patients with severe eosinophilic asthma, irrespective of atopic status or HDM sensitivity.

Graphical abstract

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Keywords:

• allergens and epitopes
• eosinophils
• asthma
• asthma treatments
• biologics

Abbreviations

ACQ, Asthma Control Questionnaire; CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FeNO, fractional exhaled nitric oxide; HDM, house dust mite; ICS, inhaled corticosteroid; IgE, immunoglobulin E; IL, interleukin; IV, intravenously; LS, least squares; mITT, modified intent-to-treat population; NE, rate ratio could not be estimated due to insufficient patient numbers; OCS, oral corticosteroid; SC, subcutaneously.

Data Sharing Statement

Anonymized individual participant data and study documents for the parent study can be requested for further research from www.clinicalstudydatarequest.com.

Ethics Approval and Informed Consent

This was a post hoc analysis of anonymized patient data from study MEA115588/NCT01691521. The primary study was conducted in accordance with the Declaration of Helsinki, the International Council on Harmonization Good Clinical Practice guideline, and the applicable country-specific regulatory requirements. The local institutional review board or ethics committee at each study center oversaw trial conduct and documentation. All patients provided written informed consent.

Acknowledgments

This secondary analysis and the primary study (MEA115588/NCT01691521) were funded by GlaxoSmithKline (GSK). Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing and referencing) was provided by Elizabeth Hutchinson, PhD, CMPP and Laura Gardner, PhD, CMPP, at Fishawack Indicia Ltd, part of Fishawack Health, UK, and was funded by GSK.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

CMP, SM and SWY are all employees and shareholders of GSK. FCA is a former employee of GSK, holds GSK stocks/shares and is currently employed by Avillion US, Inc. MI has received fees from Actelion, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, MSD, Novartis and Teva. JAD has received personal fees from AstraZeneca, GSK, Novartis and Sanofi-Aventis, has been an investigator for AstraZeneca, GSK, Novartis, Sanofi-Aventis, Grifols, BioCryst, CSL Ltd and Equilium, and holds shares in CSL Ltd. AB has received fees from GSK, Regeneron, Chiesi, AstraZeneca, Teva, Novartis and Boehringer Ingelheim and been an investigator for Novartis and AstraZeneca. The authors report no other conflicts of interest in this work.

Additional information

Funding

This post hoc, secondary subgroup analysis and the primary study (MEA115588/NCT01691521) were funded by GSK.