Association Between Baseline Therapy and Flare Reduction in Mepolizumab-Treated Patients With Hypereosinophilic Syndrome

Abstract

Background: Current standard-of-care treatments for hypereosinophilic syndrome (HES) include oral corticosteroids (OCS) and immunosuppressive/cytotoxic (IS/CT) therapies. The anti-IL-5 monoclonal antibody mepolizumab has also recently been approved for patients with this disease. The objective of this analysis was to assess the relationship between baseline therapy and flare reduction in patients with HES treated with mepolizumab, using data from the Phase III 200622 study (NCT02836496).

Methods: In the double-blind, parallel-group 200622 study, eligible patients were ≥12 years old and had HES for ≥6 months, ≥2 flares in the previous 12 months, blood eosinophils ≥1000 cells/μL at screening and ≥4 weeks' stable HES therapy. Patients were randomised (1:1) to receive mepolizumab 300 mg subcutaneously or placebo every 4 weeks for 32 weeks plus their existing HES therapy. This post hoc, descriptive analysis assessed the effect of baseline HES therapy [IS/CT (± OCS), OCS No IS/CT, and No IS/CT/OCS] on the proportion of patients with ≥1 flare during the study period, the annualised rate of flares, time to first flare, and the proportion of patients with ≥1 flare during Weeks 20─32, with mepolizumab versus placebo.

Results: Mepolizumab treatment was associated with a decrease in the proportion of patients who experienced ≥1 flare during the study period in all baseline therapy groups versus placebo (32-96% reduction). Similarly, the probability of a flare was lower with mepolizumab (14.3-31.4%) than placebo (35.7-74.1%) in all baseline therapy groups, as was the annualised flare rate (0.22-0.68 vs 1.14-1.62). The proportion of patients who experienced ≥1 flare during Weeks 20-32 was reduced with mepolizumab versus placebo for all baseline therapy groups (55-85% reduction). For all endpoints, the greatest effect of mepolizumab treatment was seen in the IS/CT (± OCS) group.

Conclusions: Patients with poorly controlled HES are likely to achieve clinical benefit with mepolizumab in terms of flare reduction, regardless of their baseline therapy.

Clinical trial registration: (https://ichgcp.net/clinical-trials-registry/NCT02836496).

Keywords: biologics; clinical immunology; eosinophils; hypereosinophilic syndrome; immunosuppressive therapy; mepolizumab; oral corticosteroids.

Conflict of interest statement

AR declares consultancy and advisory board attendance for Blueprint, Novartis, Incyte, Celgene, Abbvie and AOP, and participation as a trial investigator for Blueprint, Novartis, Incyte, Celgene, Abbvie, AOP and GSK. GL reports consulting or advisory fees from Takeda, AstraZeneca, Shire, and Sanofi Genzyme and research grant and travel and accommodation expenses from Octapharma, Takeda, and GSK, Shire. MCC has received consultancy fees from, Janssen and GSK, research grant from Kiniksa Pharmaceuticals, lecturing fees from Vifor and GSK and Roche, and Scientific meeting expenses from Roche and Kiniksa Pharmaceuticals and GSK. NK, EM, SWY and JS are all employees of GSK and own stock/shares in GSK. This study received funding from GlaxoSmithKline. The funder had the following involvement with the study: this post hoc analysis, the parent study (GSK ID: 200622, Clinical Trial.gov number NCT02836496) and the editorial support provided were funded by GlaxoSmithKline.

Copyright © 2022 Reiter, Lefevre, Cid, Kwon, Mavropolou, Yancey and Steinfeld.

Figures

Figure 1

Odds of a patient experiencing ≥1 flare with mepolizumab versus placebo during the 32-week treatment period by baseline treatment type. *These values were originally reported in Roufosse et al., 2020. CI, confidence interval; CT, cytotoxic therapy; HES, hypereosinophilic syndrome; IS, immunosuppressive therapy; OCS, oral corticosteroid; SC, subcutaneous.

Figure 2

Annualised rate of flares with mepolizumab versus placebo by baseline treatment type. *These values were originally reported in Roufosse et al., 2020. CI, confidence interval; CT, cytotoxic therapy; HES, hypereosinophilic syndrome; IS, immunosuppressive therapy; OCS, oral corticosteroid; SC, subcutaneous.

Figure 3

Kaplan-Meier analysis of time to first flare with mepolizumab versus placebo in (A) IS/CT ( ± OCS), (B) OCS No IS/CT and (C) No IS/CT/OCS subgroups. *Hazard ratio (mepolizumab 300mg SC/placebo) calculated by Cox proportional hazards regression analysis adjusted for baseline OCS dose. CI, confidence interval; CT, cytotoxic therapy; IS, immunosuppressive therapy; mepo, mepolizumab; OCS, oral corticosteroid; SC, subcutaneous.

Figure 4

Odds of a patient experiencing ≥1 flare with mepolizumab versus placebo during Week 20 though Week 32 by baseline treatment type. *These values were originally reported in Roufosse et al., 2020. CI, confidence interval; CT, cytotoxic therapy; HES, hypereosinophilic syndrome; IS, immunosuppressive therapy; OCS, oral corticosteroid; SC, subcutaneous.