Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics

Mark C Liu,Miguel Bergna,Jay Azmi,Gilles Devouassoux,Xavier Munoz,Robert G Price,Dalal Mouneimne,Bradley Chipps,Kenneth R Chapman,Steven G Smith,Dmitry V Galkin,Frank C Albers

doi:10.1186/s12931-021-01733-9

Abstract

BackgroundThe OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. The objective of this analysis was to assess the proportion of patients achieving pre-defined improvements in up to four efficacy outcomes and the relationship between patient baseline characteristics and treatment response.MethodsThis was a post hoc analysis of OSMO study data (GSK ID:204471; ClinicalTrials.gov No. NCT02654145). Patients with severe eosinophilic asthma uncontrolled by high-dose inhaled corticosteroids, other controller(s) and omalizumab subcutaneously (≥ 4 months) were switched to mepolizumab 100 mg administered subcutaneously. Endpoints included the proportion of responders—i.e. patients achieving a pre-defined clinical improvement in ≥ 1 of the following outcomes: (1) Asthma Control Questionnaire (ACQ)-5 score (≥ 0.5-points), (2) St George’s Respiratory Questionnaire (SGRQ) total score (≥ 4-points), (3) pre-bronchodilator forced expiratory volume in 1s (FEV1; ≥ 100 mL), all at Week 32, and (4) annualised rate of clinically significant exacerbations (≥ 50% reduction).ResultsOf the 145 patients included, 94%, 83%, 63% and 31% were responders for ≥ 1, ≥ 2, ≥ 3 and 4 outcomes, respectively; 75% and 78% were ACQ-5 and SGRQ score responders, and 50% and 69% were FEV1 and exacerbation responders. Subgroup analyses demonstrated improvements irrespective of baseline blood eosinophil count, prior omalizumab treatment regimen/duration, comorbidities, prior exacerbation history, maintenance oral corticosteroid use, ACQ-5 and SGRQ scores, and body weight/body mass index.ConclusionsAfter switching to mepolizumab, almost all patients with uncontrolled severe eosinophilic asthma on omalizumab achieved a beneficial response in ≥ 1 clinical outcome. Improvements were observed regardless of baseline characteristics.Trial registration This manuscript is a post hoc analysis of data from the OSMO study. ClinicalTrials.gov, NCT02654145. Registered January 13, 2016.

Highlights

The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab
Several clinical trials have shown that compared with placebo, mepolizumab reduces the rate of clinically significant exacerbations and maintenance oral corticosteroid (OCS) dose, and improves asthma control, health-related quality of life (HRQoL) and lung function in patients with severe eosinophilic asthma [7,8,9,10]
Patients who achieved a response in all four efficacy outcomes typically experienced a greater number of exacerbations in the prior year, had lower pre- and postbronchodilator Forced expiratory volume in 1s (FEV1), and had a greater occurrence of nasal polyps versus those achieving fewer pre-defined clinical improvements

Summary

Introduction

The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. Mepolizumab is a humanised, monoclonal antibody that binds to and inactivates interleukin (IL)-5, inhibiting IL-5 signalling and blocking eosinophil survival and proliferation [4] It is approved for the treatment of patients with severe eosinophilic asthma ≥ 6 years of age in multiple regions worldwide, for patients with eosinophilic granulomatosis with polyangiitis in several countries including the USA, Japan and Canada, and has recently been approved for use in patients with hyperesoinophilic syndrome in the US [5, 6]. Several clinical trials have shown that compared with placebo, mepolizumab reduces the rate of clinically significant exacerbations and maintenance oral corticosteroid (OCS) dose, and improves asthma control, HRQoL and lung function in patients with severe eosinophilic asthma [7,8,9,10]. Not all patients treated with omalizumab achieve adequate symptom control and reduced exacerbations [19, 20]

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Discussion

Conclusion