Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study

Abstract

What is already known about this topic? A phase III study demonstrated that compared with placebo, 4-weekly add-on mepolizumab (300 mg subcutaneously) reduced flares in patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor a (FIP1L1-PDGFRA)-negative hypereosinophilic syndrome (HES), with a positive benefiterisk profile.What does this article add to our knowledge? This open-label extension study found no new safety signals with mepolizumab treatment in patients with FIP1L1-PDGFRA-negative HES. Moreover, mepolizumab continued to control flares and blood eosinophil counts after 52 weeks of continuous treatment.How does this study impact current management guidelines? Findings from this open-label extension study provide further evidence that patients with FIP1L1-PDGFRA-negative HES are likely to benefit from treatment with mepolizumab and may be able to reduce oral corticosteroid use.BACKGROUND: A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor aenegative hypereosinophilic syndrome (HES) and two or more flares in the previous year. OBJECTIVE: To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab. METHODS: Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300 mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count. RESULTS: Of 104 patients who completed the double-blind study, 98% (previous placebo, n [ 52; previous mepolizumab, n [ 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported

The emerging roles of eosinophils: Implications for the targeted treatment of eosinophilic-associated inflammatory conditions

“…Similarly, a phase III trial let to mepolizumab approval by EMA for FIP1-like-1-platelet-derived growth factor receptor α-negative HES, given subcutaneously at a dose of 300 mg every 4 weeks versus placebo, and added on HES therapy ( Roufosse et al, 2020 ). While as safe as standard of care, the proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo, and the open-label extension of the trial confirmed long-term control of disease flares, blood eosinophil counts, plus reductions in corticosteroid use ( Gleich et al, 2021 ).…”

Mepolizumab in Hypereosinophilic Syndromes: Proposed Therapeutic Algorithm

“…[1][2][3][4][5] Based on this knowledge, IL-5etargeting treatment approaches have been developed in the past 2 decades. [6][7][8][9][10][11][12] Mepolizumab is a humanized monoclonal antibody that binds to IL-5 and blocks IL-5 effects, including IL-5einduced growth, survival, migration, and activation of eosinophils. Mepolizumab has been approved for treatment of severe eosinophil-related asthma, eosinophilic granulomatosis with polyangiitis, and HES associated with chronic rhinosinusitis with nasal polyps.…”

“…For the latter group of HES, two clinical trials, NCT02836496 and NCT03306043, have demonstrated efficacy of mepolizumab without major safety issues, leading to the approval of the drug. 8,11,12 In these trials, mepolizumab reduced the frequency of flares, fatigue severity, corticosteroid doses, and eosinophil counts in patients with nonclonal HES. 8,11,12 Although the mechanism of drug action in cytokine-triggered (reactive) HES is obvious, it remains unclear whether the drug acts in all patient subsets and whether responses depend on (and thus can be predicted by) eosinophil counts or serum IL-5 levels.…”

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

“…However, the OCS-sparing effect of these therapies has not been demonstrated in randomised controlled clinical trials and their use can be limited by adverse effects ( 13 – 15 ). The OCS-sparing effect of mepolizumab in severe eosinophilic asthma and EGPA is well-established ( 17 – 19 ) and there is emerging evidence of an OCS sparing effect of mepolizumab in patients with HES ( 20 , 21 ). In the 20-week open label extension of the 200622 study (205203/NCT03306043) a ≥50% reduction in OCS daily dose was achieved by 28% of patients using OCS during the first 4 weeks of the study ( 21 ).…”

“…The OCS-sparing effect of mepolizumab in severe eosinophilic asthma and EGPA is well-established ( 17 – 19 ) and there is emerging evidence of an OCS sparing effect of mepolizumab in patients with HES ( 20 , 21 ). In the 20-week open label extension of the 200622 study (205203/NCT03306043) a ≥50% reduction in OCS daily dose was achieved by 28% of patients using OCS during the first 4 weeks of the study ( 21 ). Mepolizumab may therefore offer the additional benefit of OCS reduction for patients requiring chronic or repeated courses of OCS.…”