Mepolizumab and High-Baseline EDN Linked to Lower Asthma Exacerbation Rates

This article is part of MPR‘s coverage of the American Thoracic Society International Conference, taking place in Dallas, Texas. Our staff will report on medical research related to asthma and other respiratory conditions, conducted by experts in the field. Check back regularly for more news from ATS 2019.

DALLAS — Baseline blood eosinophil counts have shown a positive association with certain biomarkers, with mepolizumab-treated individuals with high baseline levels of eosinophil-derived neurotoxin (EDN) experiencing the greatest decrease in exacerbation rates. This research was presented at the American Thoracic Society International Conference, held May 17-22, in Dallas, Texas.

This post hoc analysis included participants from the 32-week Mepolizumab as Adjunctive Therapy in Patients With Severe Asthma study (ClinicalTrials.gov Identifier: NCT01691521). Participants with severe eosinophilic asthma were randomly assigned to treatment every 4 weeks with subcutaneous mepolizumab 100 mg, intravenous mepolizumab 75 mg, or placebo in a 1:1:1 ratio. Biomarkers of interest included EDN; eosinophil cationic protein (ECP); interleukin-13; C-C motif chemokine ligand chemokines 13, 17, and 22; periostin; and eotaxin-1, with samples collected randomly at initiation and at end of study. Baseline blood eosinophil count was used to assess biomarker levels, stratified into levels of <150, 150 to <300, 300 to <500, and ≥500 cells/μL. The effect of mepolizumab on clinical outcomes and blood eosinophil levels was evaluated using baseline EDN or ECP levels that were either greater than median value (high) or less than or equal to median value (low).

Patients with higher eosinophil levels generally showed higher biomarker levels, with the exception of eotaxin-1, which showed a negative association with eosinophil levels. In patients treated with mepolizumab, the week 32 to baseline ratio of eosinophil counts was lower in patients with high vs low baseline EDN (0.10 vs 0.19) and ECP (0.10 vs 0.18) levels. Eosinophil counts decreased regardless of these levels, with a ratio of mepolizumab to placebo of 0.14 (95% CI, 0.11-0.19) in patients with high EDN, 0.17 (95% CI, 0.13-0.22) among patients with low EDN, 0.14 (95% CI, 0.11-0.18) in patients with high ECP, and 0.17 (95% CI, 0.13-0.23) in patients with low ECP. Better placebo-adjusted improvements in exacerbations were observed in patients with high vs low baseline EDN but not high vs low baseline ECP. Improvements in prebronchodilator forced expiratory volume in 1 second were greater in those with high vs low baseline EDN or ECP using mepolizumab, as were improvements in St. George’s Respiratory Questionnaire and Asthma Control Questionnaire-5.

The study researchers concluded, “At baseline, blood eosinophil counts were positively correlated with the assessed biomarkers, except for eotaxin-1. High baseline EDN was associated with the largest reduction in exacerbation rates in mepolizumab-treated patients; differences in other clinical outcomes were numerically greater in patients with high vs low baseline EDN or ECP.”

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