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Mepolizumab is associated with a 50% reduction in the occurrence of flares in patients with uncontrolled hypereosinophilic syndrome

The humanised anti-IL5 monoclonal antibody mepolizumab is the first drug that was shown to reduce disease flares in patients with FIP1L1-PDGFRA-negative hypereosinophilic syndrome (HES). In fact, subcutaneous mepolizumab was associated with a 50% reduction in the occurrence of flares. Compared to placebo, mepolizumab reduced both the risk of a flare and the annualized rate of flares by 66% during the study period. No unexpected safety signals were identified. Overall, these results suggest that patients with relapsing HES may benefit from mepolizumab treatment.


HES makes up a rare group of disorders that are characterised by elevated eosinophil levels in the blood and/or tissues and eosinophil-mediated tissue/organ damage and dysfunction. Mepolizumab is a humanised anti-IL5 monoclonal antibody that is approved for the use in patients with other eosinophilic diseases such as severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis. In previous clinical studies including patients with HES, mepolizumab (750 mg, intravenously) reduced the blood eosinophil counts and decreased the need for oral corticosteroids. However, the impact of mepolizumab on HES disease activity remains unclear. The aim of the study presented by prof. F. Roufosse at the 2020 EHA meeting was to investigate the clinical efficacy and safety of mepolizumab 300 mg subcutaneously versus placebo in patients with HES in a randomised phase III trial.

Eligible patients were ≥ 12 years old, diagnosed with FIP1L1-PDGFRA-negative HES ≥ 6 months, and had at least two flares (worsening of HES-related clinical symptoms or blood eosinophil counts [BEC] requiring therapy escalation) in the previous 12 months, with a blood eosinophil count ≥1000 cells/μL and at least four weeks stable doses of HES therapy at screening. Patients (N=108) were randomised (1:1) to subcutaneous mepolizumab (300 mg) or placebo, plus their baseline HES therapy, every 4 weeks for 32 weeks. After week 32, patients were eligible to continue to receive mepolizumab every four weeks as part of an open-label extension study. The primary outcome was the proportion of patients who experienced a flare during the study. Flares were defined as HES-related clinical manifestations requiring either an increased maintenance oral corticosteroids (OCS) dose ≥10 mg/day for 5 days or an increase in or addition of any cytotoxic and/or immunosuppressive therapies or ≥2 courses of blinded rescue OCS during the study.


The proportion of patients with at least one flare or who withdrew from the study across the full study period was 50% lower for patients receiving mepolizumab than what was seen with placebo (28% versus 56%, Odds ratio [95% CI]: 0.28 [0.12- 0.64], p=0.003). In addition, both the annualized rate of flares (Odds ratio [95% CI]: 0.34 [0.19-0.63], p ≤0.001) and the risk of first flare (HR [95% CI]: 0.34 [0.18-0.67], p=0.002) over the treatment period were 66% lower with mepolizumab than with placebo. In addition, the occurrence of flares during weeks 20-32 was decreased with mepolizumab. In fact, in the placebo arm, 35% of patients experienced a flare during this period as compared to only 17% with mepolizumab (Odds ratio [95%CI]: 0.33 [0.13-0.85], p=0.022). As such, this finding reflects that the effect of mepolizumab on flares was sustained throughout the study period. In addition, BEC were markedly reduced with mepolizumab versus placebo and the BEC reached a plateau at the third mepolizumab injection.

Proportions of patients experiencing on-treatment adverse events (AEs) and serious AEs (SAEs) were similar with mepolizumab and placebo (AEs: 89% and 87%; SAEs: 19% and 15%, respectively). One fatality (not considered to be related to study treatment) was reported in the mepolizumab group. The most common on-treatment AEs in the mepolizumab arm were bronchitis (15%), upper respiratory tract infection (15%), headache (13%) and nasopharyngitis (13%).


Mepolizumab (300 mg subcutaneously) was associated with a 50% reduction in the occurrence of flares compared to the standard-of-care plus placebo, in patients with uncontrolled HES. The risk of a flare and the annualized rate of flares were both 66% lower during the study period for patients receiving mepolizumab versus placebo. No new safety signals were identified. As such, mepolizumab is the first treatment shown to reduce disease flares in patients with FIP1L1-PDGFRA-negative HES and the findings from this study represent an important advance for the management of this rare, debilitating disease.


Roufosse F, Kahn JE, Gleich GJ, et al. Efficacy and safety of mepolizumab in hypereosinophilic syndrome: a phase III, randomized, placebo-controlled trial. Presented at EHA 2020; Abstract S219.

Speaker Florence Roufosse

Florence Roufosse

Florence Roufosse, MD, PhD, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium


See: Keyslides


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