Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL) : a randomised, multicentre, open-label, phase 4 study
Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved..
BACKGROUND: Stepwise intensification of inhaled corticosteroids (ICS) is routine for severe eosinophilic asthma, despite some poor responses to high-dose ICS. Dose reductions are recommended in patients responding to biologics, but little supporting safety evidence exists.
METHODS: SHAMAL was a phase 4, randomised, open-label, active-controlled study done at 22 study sites in four countries. Eligible participants were adults (aged ≥18 years) with severe eosinophilic asthma and a five-item Asthma Control Questionnaire score below 1·5 and who received at least three consecutive doses of benralizumab before screening. We randomly assigned patients (3:1) to taper their high-dose ICS to a medium-dose, low-dose, and as-needed dose (reduction group) or continue (reference group) their ICS-formoterol therapy for 32 weeks, followed by a 16-week maintenance period. The primary endpoint was the proportion of patients reducing their ICS-formoterol dose by week 32. The primary outcome was assessed in the reduction group, and safety analyses included all randomly assigned patients receiving study treatment. This study is registered at ClinicalTrials.gov, NCT04159519.
FINDINGS: Between Nov 12, 2019, and Feb 16, 2023, we screened and enrolled in the run-in period 208 patients. We randomly assigned 168 (81%) to the reduction (n=125 [74%]) and reference arms (n=43 [26%]). Overall, 110 (92%) patients reduced their ICS-formoterol dose: 18 (15%) to medium-dose, 20 (17%) to low-dose, and 72 (61%) to as-needed only. In 113 (96%) patients, reductions were maintained to week 48; 114 (91%) of patients in the reduction group had zero exacerbations during tapering. Rates of adverse events were similar between groups. 91 (73%) patients had adverse events in the reduction group and 35 (83%) in the reference group. 17 patients had serious adverse events in the study: 12 (10%) in the reduction group and five (12%) in the reference group. No deaths occurred during the study.
INTERPRETATION: These findings show that patients controlled on benralizumab can have meaningful reductions in ICS therapy while maintaining asthma control.
FUNDING: AstraZeneca.
| Errataetall: |
ErratumIn: Lancet. 2024 Mar 23;403(10432):1140. - PMID 38521558 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:403 |
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| Enthalten in: |
Lancet (London, England) - 403(2024), 10423 vom: 20. Jan., Seite 271-281 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jackson, David J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.01.2024 Date Revised 23.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT04159519 ErratumIn: Lancet. 2024 Mar 23;403(10432):1140. - PMID 38521558 Citation Status MEDLINE |
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| doi: |
10.1016/S0140-6736(23)02284-5 |
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| 245 | 1 | 0 | |a Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL) |b a randomised, multicentre, open-label, phase 4 study |
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| 500 | |a ClinicalTrials.gov: NCT04159519 | ||
| 500 | |a ErratumIn: Lancet. 2024 Mar 23;403(10432):1140. - PMID 38521558 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a BACKGROUND: Stepwise intensification of inhaled corticosteroids (ICS) is routine for severe eosinophilic asthma, despite some poor responses to high-dose ICS. Dose reductions are recommended in patients responding to biologics, but little supporting safety evidence exists | ||
| 520 | |a METHODS: SHAMAL was a phase 4, randomised, open-label, active-controlled study done at 22 study sites in four countries. Eligible participants were adults (aged ≥18 years) with severe eosinophilic asthma and a five-item Asthma Control Questionnaire score below 1·5 and who received at least three consecutive doses of benralizumab before screening. We randomly assigned patients (3:1) to taper their high-dose ICS to a medium-dose, low-dose, and as-needed dose (reduction group) or continue (reference group) their ICS-formoterol therapy for 32 weeks, followed by a 16-week maintenance period. The primary endpoint was the proportion of patients reducing their ICS-formoterol dose by week 32. The primary outcome was assessed in the reduction group, and safety analyses included all randomly assigned patients receiving study treatment. This study is registered at ClinicalTrials.gov, NCT04159519 | ||
| 520 | |a FINDINGS: Between Nov 12, 2019, and Feb 16, 2023, we screened and enrolled in the run-in period 208 patients. We randomly assigned 168 (81%) to the reduction (n=125 [74%]) and reference arms (n=43 [26%]). Overall, 110 (92%) patients reduced their ICS-formoterol dose: 18 (15%) to medium-dose, 20 (17%) to low-dose, and 72 (61%) to as-needed only. In 113 (96%) patients, reductions were maintained to week 48; 114 (91%) of patients in the reduction group had zero exacerbations during tapering. Rates of adverse events were similar between groups. 91 (73%) patients had adverse events in the reduction group and 35 (83%) in the reference group. 17 patients had serious adverse events in the study: 12 (10%) in the reduction group and five (12%) in the reference group. No deaths occurred during the study | ||
| 520 | |a INTERPRETATION: These findings show that patients controlled on benralizumab can have meaningful reductions in ICS therapy while maintaining asthma control | ||
| 520 | |a FUNDING: AstraZeneca | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Multicenter Study | |
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| 700 | 1 | |a Heaney, Liam G |e verfasserin |4 aut | |
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| 700 | 1 | |a Baglivo, Ilaria |e investigator |4 oth | |
| 700 | 1 | |a Colantuono, Stefania |e investigator |4 oth | |
| 700 | 1 | |a Jackson, David |e investigator |4 oth | |
| 700 | 1 | |a Skowasch, Dirk |e investigator |4 oth | |
| 700 | 1 | |a Di Marco, Fabiano |e investigator |4 oth | |
| 700 | 1 | |a Couturaud, Francis |e investigator |4 oth | |
| 700 | 1 | |a Käßner, Frank |e investigator |4 oth | |
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| 700 | 1 | |a Knetsch, Kornelia |e investigator |4 oth | |
| 700 | 1 | |a Preuß, Jasmin |e investigator |4 oth | |
| 700 | 1 | |a Devouassoux, Gilles |e investigator |4 oth | |
| 700 | 1 | |a Milger-Kneidinger, Katrin |e investigator |4 oth | |
| 700 | 1 | |a Heaney, Liam |e investigator |4 oth | |
| 700 | 1 | |a Jerrentrup, Lukas |e investigator |4 oth | |
| 700 | 1 | |a Humbert, Marc |e investigator |4 oth | |
| 700 | 1 | |a Jandl, Margret |e investigator |4 oth | |
| 700 | 1 | |a Timmermann, Hartmut |e investigator |4 oth | |
| 700 | 1 | |a Probst, Beatrice |e investigator |4 oth | |
| 700 | 1 | |a D'Amato, Maria |e investigator |4 oth | |
| 700 | 1 | |a Hoffmann, Martin |e investigator |4 oth | |
| 700 | 1 | |a Bonniaud, Philippe |e investigator |4 oth | |
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| 700 | 1 | |a Girodet, Pierre-Olivier |e investigator |4 oth | |
| 700 | 1 | |a Berger, Patrick |e investigator |4 oth | |
| 700 | 1 | |a Nasser, Shuaib |e investigator |4 oth | |
| 700 | 1 | |a Fry, Stéphanie |e investigator |4 oth | |
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| 700 | 1 | |a Aries, Sven Philip |e investigator |4 oth | |
| 700 | 1 | |a Koehler, Thomas |e investigator |4 oth | |
| 700 | 1 | |a Harrison, Timothy |e investigator |4 oth | |
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