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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

The 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.

Methods

This 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 (FEV ₁; ≥ 100 mL), all at Week 32, and (4) annualised rate of clinically significant exacerbations (≥ 50% reduction).

Results

Of 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 FEV ₁ 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.

Conclusions

After 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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12931-021-01733-9.

Related collections

Most cited references 28

Record: found
Abstract: found
Article: not found

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.

0 comments Cited 702 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

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.

0 comments Cited 671 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

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.).

0 comments Cited 401 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Kenneth R. Chapman:

ORCID: http://orcid.org/0000-0002-2498-9859

ken.chapman.airways@gmail.com

Journal

Journal ID (nlm-ta): Respir Res

Journal ID (iso-abbrev): Respir Res

Title: Respiratory Research

Publisher: BioMed Central (London )

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Electronic): 10 May 2021

Publication date PMC-release: 10 May 2021

Publication date (Print): 2021

Volume: 22

Electronic Location Identifier: 144

Affiliations

[1 ]GRID grid.411940.9, ISNI 0000 0004 0442 9875, Divisions of Allergy and Clinical Immunology, Pulmonary and Critical Care Medicine, , Johns Hopkins Asthma and Allergy Center, ; Baltimore, MD USA

[2 ]GRID grid.418632.a, Capital Allergy and Respiratory Disease Center, ; Sacramento, CA USA

[3 ]GRID grid.411083.f, ISNI 0000 0001 0675 8654, Pulmonology Department, , Hospital Universitari Vall d’Hebron, ; Barcelona, Spain

[4 ]GRID grid.413448.e, ISNI 0000 0000 9314 1427, Ciber Enfermedades Respiratorias, ; Madrid, Spain

[5 ]GRID grid.413306.3, ISNI 0000 0004 4685 6736, Service de Pneumologie, , Hôpital de la Croix Rousse, Hospices Civils de Lyon, UCB Lyon, ; Lyon, France

[6 ]Respiratory Research, CEMER, Vicente Lopez, Buenos Aires, Argentina

[7 ]GRID grid.418019.5, ISNI 0000 0004 0393 4335, Respiratory Therapeutic Area, , GSK, ; Research Triangle Park, NC USA

[8 ]GRID grid.418236.a, ISNI 0000 0001 2162 0389, Biostatistics, , GSK, ; Stevenage, Hertfordshire UK

[9 ]GRID grid.418019.5, ISNI 0000 0004 0393 4335, Global Respiratory Medical Franchise, , GSK, ; Research Triangle Park, NC USA

[10 ]GRID grid.418236.a, ISNI 0000 0001 2162 0389, Respiratory TAU, GSK, ; Uxbridge, Middlesex UK

[11 ]Global Medical Affairs, GSK House, Brentford, Middlesex UK

[12 ]GRID grid.231844.8, ISNI 0000 0004 0474 0428, Asthma and Airway Centre, , University Health Network, University of Toronto, ; Toronto, ON Canada

[13 ]GRID grid.470366.0, Present Address: Chiesi USA, ; Cary, NC USA

[14 ]Present Address: Avillion US Inc, Northbrook, IL USA

Author information

Kenneth R. Chapman http://orcid.org/0000-0002-2498-9859

Article

Publisher ID: 1733

DOI: 10.1186/s12931-021-01733-9

PMC ID: 8111733

PubMed ID: 33971856

SO-VID: d245ab8c-078c-4054-825e-877eb6948435

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 25 February 2021

Date accepted : 25 April 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100002066, GlaxoSmithKline foundation;

Award ID: 204471

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: asthma,asthma treatment,biologics,eosinophils

Data availability:

ScienceOpen disciplines: Respiratory medicine

Keywords: asthma, asthma treatment, biologics, eosinophils

Comments

Comment on this article

scite_

Cited by 6

See all cited by

Most referenced authors 384

See all reference authors

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

Read this article at

Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Related collections

Inflamed lung in vitro co-culture models

Most cited references 28

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.

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 544

Cited by 6

Most referenced authors 384