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Anti-IL5 Therapies for Asthma (Review) Cochrane Database of Systematic Reviews Anti-IL5 therapies for asthma (Review) Farne HA, Wilson A, Powell C, Bax L, Milan SJ Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti-IL5 therapies for asthma. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD010834. DOI: 10.1002/14651858.CD010834.pub3. www.cochranelibrary.com Anti-IL5 therapies for asthma (Review) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 6 OBJECTIVES ..................................... 7 METHODS ...................................... 7 Figure1. ..................................... 9 RESULTS....................................... 11 Figure2. ..................................... 13 Figure3. ..................................... 14 ADDITIONALSUMMARYOFFINDINGS . 19 DISCUSSION ..................................... 27 AUTHORS’CONCLUSIONS . 29 ACKNOWLEDGEMENTS . 29 REFERENCES ..................................... 30 CHARACTERISTICSOFSTUDIES . 46 DATAANDANALYSES. 81 Analysis 1.1. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 1 Rate of exacerbations requiring systemic corticosteroids. ................................. 84 Analysis 1.2. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 2 Rate of exacerbations requiring emergency department treatment or admission. ...... 85 Analysis 1.3. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 3 Rate of exacerbations requiring admission. 85 Analysis 1.4. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 4 Health-related quality of life (ACQ). 86 Analysis 1.5. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 5 Health-related quality of life (SGRQ). 87 Analysis 1.6. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 6 Pre-bronchodilator FEV1 (litres). 88 Analysis 1.7. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 7 Serious adverse events. 88 Analysis 1.8. Comparison 1 Mepolizumab (SC) versus placebo, Outcome 8 Adverse events leading to discontinuation. 89 Analysis 2.1. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 1 Rate of clinically significant exacerbations. 90 Analysis 2.2. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 2 Rate of exacerbations requiring emergency department treatment or admission. ...... 91 Analysis 2.3. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 3 Rate of exacerbations requiring admission. 91 Analysis 2.4. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 4 People with one or more exacerbations. 92 Analysis 2.5. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 5 Health-related quality of life (AQLQ). 93 Analysis 2.6. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 6 Health-related quality of life (ACQ). 94 Analysis 2.7. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 7 Health-related quality of life (SGRQ). 94 Analysis 2.8. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 8 Pre-bronchodilator FEV1 (litres). 95 Analysis 2.9. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 9 Serious adverse events. 96 Analysis 2.10. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 10 Adverse events leading to discontinuation. 97 Analysis 2.11. Comparison 2 Mepolizumab (IV) versus placebo, Outcome 11 Serum eosinophil level (cells/microlitre). 98 Analysis 3.1. Comparison 3 Reslizumab (IV) versus placebo, Outcome 1 Rate of exacerbations requiring systemic corticosteroids. ................................. 98 Analysis 3.2. Comparison 3 Reslizumab (IV) versus placebo, Outcome 2 Rate of exacerbations requiring emergency department treatment or admission. ...... 99 Analysis 3.3. Comparison 3 Reslizumab (IV) versus placebo, Outcome 3 Health-related quality of life (AQLQ). 100 Analysis 3.4. Comparison 3 Reslizumab (IV) versus placebo, Outcome 4 Health-related quality of life (ACQ). 101 Analysis 3.5. Comparison 3 Reslizumab (IV) versus placebo, Outcome 5 Pre-bronchodilator FEV1 (litres). 102 Analysis 3.6. Comparison 3 Reslizumab (IV) versus placebo, Outcome 6 Serious adverse events. 103 Analysis 3.7. Comparison 3 Reslizumab (IV) versus placebo, Outcome 7 Adverse events leading to discontinuation. 104 Analysis 3.8. Comparison 3 Reslizumab (IV) versus placebo, Outcome 8 Serum eosinophil level (cells/microlitre). 105 Anti-IL5 therapies for asthma (Review) i Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Analysis 4.1. Comparison 4 Benralizumab (SC) versus placebo, Outcome 1 Rate of exacerbations requiring systemic corticosteroids. ... ... ... ... ... ... ... ... ... ... .. 106 Analysis 4.2. Comparison 4 Benralizumab (SC) versus placebo, Outcome 2 Rate of exacerbations requiring emergency department treatment or admission. 107 Analysis 4.3. Comparison 4 Benralizumab (SC) versus placebo, Outcome 3 Health-related quality of life (AQLQ mean difference).................................... 108 Analysis 4.4. Comparison 4 Benralizumab (SC) versus placebo, Outcome 4 Health-related quality of life (ACQ mean difference).................................... 109 Analysis 4.5. Comparison 4 Benralizumab (SC) versus placebo, Outcome 5 Pre-bronchodilator FEV1 (litres). 110 Analysis 4.6. Comparison 4 Benralizumab (SC) versus placebo, Outcome 6 Serious adverse events. 112 Analysis 4.7. Comparison 4 Benralizumab (SC) versus placebo, Outcome 7 Adverse events leading to discontinuation. 113 Analysis 4.8. Comparison 4 Benralizumab (SC) versus placebo, Outcome 8 Serum eosinophil level (% change from baseline). ................................... 115 ADDITIONALTABLES. 116 APPENDICES ..................................... 119 WHAT’SNEW..................................... 121 CONTRIBUTIONSOFAUTHORS . 122 DECLARATIONSOFINTEREST . 122 SOURCESOFSUPPORT . 122 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . .... 123 INDEXTERMS .................................... 123 Anti-IL5 therapies for asthma (Review) ii Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Anti-IL5 therapies for asthma Hugo A Farne1, Amanda Wilson2, Colin Powell3, Lynne Bax4, Stephen J Milan5 1Imperial College, London, UK. 2School of Nursing and Midwifery, University of Newcastle, Newcastle, Australia. 3Department of Child Health, The Division of Population Medicine, The School of Medicine, Cardiff University, Cardiff, UK. 4Lancashire Care NHS Foundation Trust, Preston, UK. 5Lancaster Health Hub, Lancaster University, Lancaster, UK Contact address: Hugo A Farne, Imperial College, London, W2 1PG, UK. [email protected], [email protected]. Editorial group: Cochrane Airways Group. Publication status and date: New search for studies and content updated (conclusions changed), published in Issue 9, 2017. Citation: Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti-IL5 therapies for asthma. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD010834. DOI: 10.1002/14651858.CD010834.pub3. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background This review is the first update of a previously published review in The Cochrane Library (Issue 7, 2015). Interleukin-5 (IL-5) is the main cytokine involved in the activation of eosinophils, which cause airway inflammation and are a classic feature of asthma. Monoclonal antibodies targeting IL-5 or its receptor (IL-5R) have been developed, with recent studies suggesting that they reduce asthma exacerbations, improve health-related quality of life (HRQoL) and lung function. These are being incorporated into asthma guidelines. Objectives To compare the effects of therapies targeting IL-5 signalling (anti-IL-5 or anti-IL-5Rα) with placebo on exacerbations, health-related qualify of life (HRQoL) measures, and lung function in adults and children with chronic asthma, and specifically in those with eosinophilic asthma refractory to existing treatments. Search methods We searched the Cochrane Airways Trials Register, clinical trials registries, manufacturers’ websites, and reference lists of included studies. The most recent search was March 2017. Selection criteria We included randomised controlled trials comparing mepolizumab, reslizumab and benralizumab versus placebo in adults and children with asthma. Data collection and analysis Two authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by Cochrane. Main results Thirteen studies on 6000 participants met the inclusion criteria. Four used mepolizumab, four used reslizumab, and five used ben- ralizumab. One study in benralizumab was terminated early due to sponsor decision and contributed no data. The studies were pre- dominantly on people with severe eosinophilic asthma, which was similarly but variably defined. Eight included children over 12 years but these results were not reported separately. We deemed the risk of bias to be low, with all studies contributing data being of robust Anti-IL5 therapies for asthma (Review) 1 Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. methodology. We considered the quality of the evidence for all comparisons to be high overall using the GRADE scheme, with the exception of intravenous mepolizumab because this is not currently a licensed delivery route. All of the anti-IL-5 treatments assessed reduced rates of ’clinically significant’ asthma exacerbation (defined
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