Mepolizumab as opposed to placebo for asthma

Review question

We considered in this review whether taking mepolizumab is better than a placebo for people with asthma.


Asthma is an inflammatory lung condition characterised by the narrowing of the airways, breathlessness, a tight chest and reduced quality of life. By the year 2025, there may be up to 400 million people with asthma worldwide. Mepolizumab is one treatment that may help to reduce the symptoms.

Study characteristics

Eight studies compared mepolizumab treatment to a placebo in 1707 patients with asthma. Six studies only included adults. We summarised the results as they relate to quality of life, occurrence of asthma attacks needing hospital admission and side effects of mepolizumab.

Key results

We found that patients with severe asthma who had high levels of eosinophils (inflammatory cells in the blood stream) benefited from taking mepolizumab through improved quality of life and reduced asthma attacks. There was no benefit in terms of lung function. We have avoided making recommendations because we think that further research is needed to clarify aspects such as dosage and length of treatment as well as which patients might benefit the most.

Authors' conclusions: 

It is not possible to draw firm conclusions from this review with respect to the role of mepolizumab in patients with asthma. Our confidence in the results of this review are limited by the fact that the intravenous route is not currently licensed for mepolizumab, and the evidence for the currently licenced subcutaneous route is limited to a single study in participants with severe eosinophilic asthma.

The currently available studies provide evidence that mepolizumab can lead to an improvement in health-related quality of life scores and reduce asthma exacerbations in people with severe eosinophilic asthma.

Further research is needed to clarify which subgroups of patients with asthma could potentially benefit from this treatment. Dosage, ideal dosing regimens and duration of treatment need to be clarified, as the studies included in this review differed in their protocols. There are no studies reporting results from children, so we cannot comment on treatment for this age group. At the present time, larger studies using licenced treatment regimens are required to establish the role of mepolizumab in the treatment of severe asthma.

Read the full abstract...

Mepolizumab is a human monoclonal antibody against interleukin-5 (IL-5), the main cytokine involved in the activation of eosinophils, which in turn causes airway inflammation. Recent studies have suggested these agents may have a role in reducing exacerbations and improving health-related quality of life (HRQoL). There are no recommendations for the use of mepolizumab in adults or children in the recent update of the BTS/SIGN guidelines (BTS/SIGN 2014).


To compare the effects of mepolizumab with placebo on exacerbations and HRQoL in adults and children with chronic asthma.

Search strategy: 

We searched the Cochrane Airways Group Register (CAGR) of trials, clinical trial registries, manufacturers' websites and the reference lists of included studies. Searches were conducted in November 2013 and updated in November 2014.

Selection criteria: 

We included randomised controlled trials comparing mepolizumab 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 The Cochrane Collaboration.

Main results: 

Eight studies on 1707 participants met the inclusion criteria. Only two studies included children (over 12 years of age), but they did not report separate findings for the adolescents. Seven studies involved intravenous mepolizumab alone; one included a subcutaneous arm. There was heterogeneity in the severity and clinical pattern of asthma among the participants in the eight studies, varying from mild to moderate atopic asthma, to persistent asthma and eosinophilic asthma with recurrent exacerbations. Selection bias was a concern in several of the studies included in this review.

Four trials compared intravenous mepolizumab to placebo in relation to HRQoL. Two studies measured scores from the Asthma Quality of Life Questionnaire (AQLQ), which showed a non-significant difference between mepolizumab and placebo (mean difference (MD) 0.21, 95% confidence interval (CI) − 0.01 to 0.44; participants = 682), in the direction favouring mepolizumab. The third study used the St. George's Respiratory Questionnaire (SGRQ) and found a significant difference between mepolizumab and placebo (MD 6.40, 95% CI 3.15 to 9.65; participants = 576), which indicated a clinically important benefit favouring mepolizumab. A fourth study noted that there was no significant difference but did not provide any data. The two studies in people with eosinophilic asthma showed a reduction in clinically significant exacerbation rates (Risk Ratio 0.52, 95% CI 0.43 to 0.64; participants = 690). However, an analysis of four studies that were not confined to people with eosinophilic asthma indicated considerable heterogeneity and no significant difference in people with one or more exacerbations between mepolizumab and placebo using a random-effects model (Risk Ratio 0.67, 95% CI 0.34 to 1.31; participants = 468; I2 = 59%).The analysis of serious adverse events indicated a significant difference favouring mepolizumab (Risk ratio 0.49, 95% CI 0.30 to 0.80; participants = 1441; studies = 5; I2 = 0%). It was not possible to combine the results for adverse events, and we deemed the quality of this evidence to be low.

A single study compared subcutaneous mepolizumab to placebo in 385 adults with severe eosinophilic asthma and found an improvement in HRQoL scores and a reduction in asthma exacerbations, including exacerbations requiring admission to hospital.