Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma - a systematic review and meta-analysis

Daniel P Henriksen, Uffe Bodtger, Kirsten Sidenius, Niels Maltbaek, Lars Pedersen, Hanne Madsen, Ehm A Andersson, Ole Norgaard, Louise Klokker Madsen, Bo L Chawes

Publikation: Bidrag til tidsskriftReviewForskningpeer review

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Resumé

Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to -0.94 annual exacerbations (95% CI -1.08;-0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

OriginalsprogEngelsk
TidsskriftEuropean Clinical Respiratory Journal
Vol/bind5
Udgave nummer1
Sider (fra-til)1536097
ISSN2001-8525
DOI
StatusUdgivet - 2018

Fingeraftryk

Interleukin-5
Drug-Related Side Effects and Adverse Reactions
Meta-Analysis
Adrenal Cortex Hormones
Placebos
Safety
Randomized Controlled Trials
Quality of Life
Outcome Assessment (Health Care)
mepolizumab
Lung
Pharmaceutical Preparations

Citer dette

Henriksen, Daniel P ; Bodtger, Uffe ; Sidenius, Kirsten ; Maltbaek, Niels ; Pedersen, Lars ; Madsen, Hanne ; Andersson, Ehm A ; Norgaard, Ole ; Madsen, Louise Klokker ; Chawes, Bo L. / Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma - a systematic review and meta-analysis. I: European Clinical Respiratory Journal. 2018 ; Bind 5, Nr. 1. s. 1536097.
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abstract = "Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53{\%} (95{\%} CI 46; 59) in favour of anti-IL-5, corresponding to -0.94 annual exacerbations (95{\%} CI -1.08;-0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25{\%} reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0{\%}). One study (N = 135) contributed with data on percentage of patients experiencing ≥50{\%} reduction inoral corticosteroid treatment, showing an effect of 20{\%} (95{\%} CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10{\%}. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.",
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Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma - a systematic review and meta-analysis. / Henriksen, Daniel P; Bodtger, Uffe; Sidenius, Kirsten; Maltbaek, Niels; Pedersen, Lars; Madsen, Hanne; Andersson, Ehm A; Norgaard, Ole; Madsen, Louise Klokker; Chawes, Bo L.

I: European Clinical Respiratory Journal, Bind 5, Nr. 1, 2018, s. 1536097.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma - a systematic review and meta-analysis

AU - Henriksen, Daniel P

AU - Bodtger, Uffe

AU - Sidenius, Kirsten

AU - Maltbaek, Niels

AU - Pedersen, Lars

AU - Madsen, Hanne

AU - Andersson, Ehm A

AU - Norgaard, Ole

AU - Madsen, Louise Klokker

AU - Chawes, Bo L

PY - 2018

Y1 - 2018

N2 - Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to -0.94 annual exacerbations (95% CI -1.08;-0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

AB - Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to -0.94 annual exacerbations (95% CI -1.08;-0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

KW - Asthma

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Interleukin-5

KW - Diagnosis

KW - Treatment

KW - Severe asthma

KW - Review

KW - Difficult-to-treat asthma

U2 - 10.1080/20018525.2018.1536097

DO - 10.1080/20018525.2018.1536097

M3 - Review

VL - 5

SP - 1536097

JO - European Clinical Respiratory Journal

JF - European Clinical Respiratory Journal

SN - 2001-8525

IS - 1

ER -