The risk of bias and the methodological quality of each study were assessed according to the Cochrane Collaboration’s tool. The trials have been evaluated for the presence of risk of bias in terms of allocation of randomisation sequence, concealment of allocation, blinding, handling of incomplete outcome data (online supplement), selective reporting bias and other sources of bias. The trials were of high methodological quality; therefore, the risk of bias among the studies was low. Summary assessment of the six key domains of risk of bias is presented in Fig. 2. The study by Bacharier et al.  was supported by the National Heart, Lung and Blood Institute (NHLBI). The WAIT study  was supported by the Medical Research Council and the National Institute for Health Research. Commercial sponsors provided the drugs and placebo, but all the final decisions were made by the NHLBI. Studies performed by Valovirta and Bisgaard et al.  were sponsored by Merck & Co. Inc. The study by Robertson et al.  was sponsored by Merck Sharp and Dohme (Australia) Pty. Ltd.Fig. 2Methodological quality summary: review authors’ judgments about each methodological quality item for each included study