Overall our study supports the use of anti-IL-5 treatments as an adjunct to standard of care in people with severe eosinophilic asthma and poor control. These treatments roughly halve the rate of asthma exacerbations in this population. There is limited evidence for improved HRQoL scores and lung function, which may not meet clinically detectable levels. There were no safety concerns regarding mepolizumab or reslizumab, and no excess serious adverse events with benralizumab, although there remains a question over adverse events significant enough to prompt discontinuation.Further research is needed on biomarkers for assessing treatment response, optimal duration and long-term effects of treatment, risk of relapse on withdrawal, non-eosinophilic patients, children (particularly under 12 years), and comparing anti-IL-5 treatments to each other and, in people eligible for both, to anti-immunoglobulin E. For benralizumab, future studies should closely monitor rates of adverse events prompting discontinuation.

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.

Some evidence suggests clear advantages for VI/FF, in combination, compared with placebo, particularly for forced expiratory volume in one second (FEV) and peak expiratory flow; however, the variety of questions addressed in the included studies did not allow review authors to draw firm conclusions. Information was insufficient for assessment of whether once-daily VI/FF was better or worse than twice-daily FP/SAL in terms of efficacy or safety. It is clear that more research is required to reduce the uncertainties that surround interpretation of these studies. It will be necessary for these findings to be replicated in other work before more robust conclusions are revealed. Only five of the 13 included studies provided data on health-related quality of life, and only six recorded asthma exacerbations. Only one study focused on paediatric patients, so no conclusions can be drawn for the paediatric population. More research is needed, particularly in the primary outcome areas selected for this review, so that we can draw firmer conclusions in the next update of this review.

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