Characterization of disease flares and impact of mepolizumab in patients with hypereosinophilic syndrome

Abstract

In patients with hypereosinophilic syndrome (HES), mepolizumab reduces the incidence of HES-related clinical signs and symptoms (flares). However, reports characterizing flare manifestations are limited. The double-blind, parallel-group 200622 trial (NCT02836496) enrolled patients ≥12 years old with HES for ≥6 months, ≥2 flares in the previous year, and screening blood eosinophil count ≥1000 cells/μL. Patients maintained ≥4 weeks stable HES therapy, before randomization (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. This post hoc analysis investigated flare manifestations and duration by re-examining the Core Assessments form and narrative recorded for each flare during the study. Flare symptoms were retrospectively categorized into constitutional, dermatological, respiratory, nasal, gastrointestinal, neurologic and other. The most frequently reported flare symptoms were constitutional (94% of flares), dermatological (82% of flares) and respiratory (72% of flares); flares reported in patients receiving mepolizumab compared with placebo were generally similar in terms of the frequency of symptoms reported. Mepolizumab was associated with a shorter median (range) duration of flares (10.0 [4, 126] days) versus placebo (26.0 [1, 154] days). In patients with HES, flares were associated with symptoms linked to multiple organ systems highlighting the challenges faced for treating flares.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT02836496, identifier NCT02836496.

Keywords: anti-interleukin-5 therapy; antibody; hypereosinophilic syndrome; mepolizumab; uncontrolled disease.

Conflict of interest statement

This study was funded by GSK (GSK ID: 200622; NCT02836496). The study sponsor had a role in study design, data collection, data analysis and interpretation, and in the writing of the study report. The sponsor did not place any restrictions on access to data or statements made in the manuscript report. Authors had full access to all study data and had final responsibility to submit the manuscript for publication. FP received advisory and speaker fees from Novartis, Bristol Myers Squibb, ARIAD Pharmaceuticals, GSK, AMGEN, Janssen, AbbVie, and Jazz Pharmaceutical, and research grants from Novartis and ARIAD Pharmaceuticals. GL received advisory fees from Shire, Takeda, AstraZeneca, and Sanofi Genzyme and has received research grants and travel/ accommodation expenses from AstraZeneca, Shire, Octapharma, and GSK. JB is an employee of GSK and own stocks/shares. NK, SWY and JS are former employees of GSK and own stocks/shares.

Copyright © 2022 Pane, Lefevre, Kwon, Bentley, Yancey and Steinfeld.

Figures

Figure 1

Frequency of flare symptoms by category and treatment group (A) and by category and term (B). *Each flare could be categorized with more than one individual symptom and across several symptom categories. SC, subcutaneous.

Figure 2

Frequency of flare symptoms by category and treatment group, stratified by baseline blood eosinophil count category. SC, subcutaneous.

Figure 3

Frequency of flare symptoms by category and treatment group, stratified by baseline therapy (IS/CT [±OCS], OCS no IS/CT, No IS/CT/OCS). HES, hypereosinophilic syndrome; IS/CT, immunosuppressive/cytotoxic therapy; OCS, oral corticosteroids; SC, subcutaneous.

Figure 4

Frequency of flare symptoms by category and treatment group, stratified by duration of HES. HES, hypereosinophilic syndrome; SC, subcutaneous.

Figure 5

Flare duration and associated symptoms for each patient. Days are the study days since randomization (Day 0 is the study start). Each light line indicates an individual patient and each darker line indicates duration of a flare in patients receiving placebo (black) or mepolizumab (light grey). Two patients (one in each treatment group) experienced flares that overlapped with a previous flare (meeting either flare definition) by less than 14 days; these cases are shown on this figure as separate flares but counted as a single flare when summarizing the number and rate of HES flares. For those flares with missing end dates (arrows), the duration of flare was calculated up to date of study withdrawal. Codes indicate symptoms experienced during any flare. C, constitutional; D, dermatological; R, respiratory; E, nasal (ear, nose, throat); G, gastrointestinal, N, neurologic; O, other; SC, subcutaneous.