REal worlD Effectiveness and Safety of Mepolizumab in a Multicentric Spanish Cohort of Asthma Patients Stratified by Eosinophils: The REDES Study

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Abstract

Background

The efficacy of mepolizumab is well documented in severe eosinophilic asthma (SEA), although the stringent selection criteria adopted by SEA clinical trials limits the generalizability of results.

Objective

Our study evaluated the effectiveness and safety of mepolizumab in patients with SEA in Spain. The primary efficacy endpoint was the change in the rate of clinically significant asthma exacerbations 12 months after starting mepolizumab compared to the baseline rate in the 12 months prior to treatment. Patients were stratified by baseline blood eosinophil counts.

Methods

We conducted a multicentric observational cohort study of SEA patients treated with mepolizumab across 24 specialized hospital asthma units in Spain. Severe exacerbation rate, lung function, oral corticosteroid use (OCS) and asthma control test (ACT) were retrospectively collected and compared during the 12-month pre- and post-mepolizumab treatment. Adverse events were also investigated.

Results

A total of 318 patients with SEA were included (mean age: 56.6 years, 69.2% female). Exacerbation rates decreased by 77.5%, and 50.6% of patients did not suffer any exacerbations during the 12 months of treatment. The difference in forced expiratory volume in 1 s (FEV1) pre- and post-bronchodilator after starting mepolizumab was 0.21 (0.46) L (95% CI 0.14–0.27) ( p < 0.001). Exacerbations and lung function significantly improved across all eosinophil subgroups. Among the 98 patients on OCS, 47.8% were able to discontinue this treatment and the mean daily dose was decreased by 59.9%. The baseline ACT score was 14.1, increasing by a mean (SD) of 6.7 points (1.9) at 12 months. Adverse events related to mepolizumab were uncommon.

Conclusions

This real-world study of SEA patients confirms that mepolizumab is effective in reducing clinically meaningful exacerbations, improving lung function, and decreasing OCS dependence and mean OCS dose at 12 months, irrespective of baseline eosinophil counts.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40265-021-01597-9.

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Most cited references 35

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International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.

Kian Fan Chung, Sally Wenzel, Jan Brozek … (2014)

Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming "uncontrolled" or that remains "uncontrolled" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.

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Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.

Ian D Pavord, Stephanie Korn, Peter Howarth … (2012)

Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0·9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506. 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2·40 per patient per year in the placebo group, 1·24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<0·0001), 1·46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0·0005), and 1·15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0·0001). Three patients died during the study, but the deaths were not deemed to be related to treatment. Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma. GlaxoSmithKline. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Mepolizumab treatment in patients with severe eosinophilic asthma.

Hector G. Ortega, Mark C Liu, Ian Pavord … (2014)

Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids. In this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory volume in 1 second (FEV1) and scores on the St. George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed. The rate of exacerbations was reduced by 47% (95% confidence interval [CI], 29 to 61) among patients receiving intravenous mepolizumab and by 53% (95% CI, 37 to 65) among those receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both comparisons). Exacerbations necessitating an emergency department visit or hospitalization were reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in those receiving placebo (P=0.02) and 98 ml greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03). The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo. Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.).

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Author and article information

Contributors

Christian Domingo Ribas:

ORCID: http://orcid.org/0000-0001-8358-773X

cdomingo@tauli.cat

Journal

Journal ID (nlm-ta): Drugs

Journal ID (iso-abbrev): Drugs

Title: Drugs

Publisher: Springer International Publishing (Cham )

ISSN (Print): 0012-6667

ISSN (Electronic): 1179-1950

Publication date (Electronic): 29 September 2021

Publication date PMC-release: 29 September 2021

Publication date (Print): 2021

Volume: 81

Issue: 15

Pages: 1763-1774

Affiliations

[1 ]GRID grid.428313.f, ISNI 0000 0000 9238 6887, Servei de Pneumologia, , Corporació Sanitària Parc Taulí, ; Parc Taulí s/n, Sabadell, 08208 Barcelona, Spain

[2 ]GRID grid.7080.f, ISNI 0000 0001 2296 0625, Universitat Autònoma de Barcelona (UAB), ; Barcelona, Spain

[3 ]H. Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain

[4 ]GRID grid.4521.2, ISNI 0000 0004 1769 9380, Universidad de Las Palmas Gran Canaria, ; Las Palmas de Gran Canaria, Spain

[5 ]GRID grid.8073.c, ISNI 0000 0001 2176 8535, H. Universitario A Coruña, ; A Coruña, Spain

[6 ]H. Universitario Doctor Peset, Valencia, Spain

[7 ]GRID grid.419327.a, ISNI 0000 0004 1768 1287, Specialty Care Medical Department, , GlaxoSmithKline, ; Madrid, Spain

Author information

Christian Domingo Ribas http://orcid.org/0000-0001-8358-773X

Article

Publisher ID: 1597

DOI: 10.1007/s40265-021-01597-9

PMC ID: 8550660

PubMed ID: 34586602

SO-VID: afc6d83d-d661-499e-a359-49d06159d553

License:

Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

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Date accepted : 20 August 2021

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REal worlD Effectiveness and Safety of Mepolizumab in a Multicentric Spanish Cohort of Asthma Patients Stratified by Eosinophils: The REDES Study

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Abstract

Background

Objective

Methods

Results

Conclusions

Supplementary Information

Related collections

NTT Journal for Theology and the Study of Religion

Most cited references 35

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.

Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.

Mepolizumab treatment in patients with severe eosinophilic asthma.

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Cited by 17

Most referenced authors 583