Abstract: One cross-over randomised controlled trial met the inclusion criteria. The trial was performed in 210 patients with moderate to severe asthma and compared the use of the LAMA tiotropium bromide with double dose beclomethasone (an ICS) using a cross-over design and 14-week treatment periods. Compared with people taking a double dose of ICS, fewer people taking a LAMA add-on had an exacerbation requiring treatment with OCS (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.22 to 1.43) or an exacerbation resulting in emergency department admission (OR 0.49, 95% CI 0.09 to 2.77), but the confidence intervals for both outcomes did not exclude the possibility that double dose ICS was more effective. Serious adverse events and exacerbations requiring hospitalisation occurred in similarly low numbers of people taking each treatment, but confidence intervals were too wide to suggest that the two treatment options were equivalent. Asthma-related quality of life was similar in both treatment groups (mean difference (MD) in change from baseline 0.10, 95% CI − 0.07 to 0.27). Those taking LAMA add-on scored slightly better on a scale measuring asthma control than those increasing their ICS dose (MD in change from baseline − 0.18, 95% CI − 0.34 to − 0.02), although the difference was clinically small. Evidence was deemed low quality for both quality of life and asthma control. There was moderate-quality evidence that participants' trough forced expiratory volume in one second (FEV1) was 100 mL better when taking LAMA add-on than with increased ICS dose (MD in change from baseline 0.10, 95% CI 0.03 to 0.17). Only one randomised trial was found, comparing tiotropium add-on to increased dose beclomethasone. Differences between the treatments were too small or imprecise to understand whether adding a LAMA to ICS is safer or more effective than increasing the dose of ICS, and there is a possibility of carry-over effects due to the study's cross-over design. LAMA add-on may lead to more improvement in lung function (FEV1) than an increased dose of ICS. The results of this review, alongside pending results from related reviews assessing the use of LAMA against other treatments, will help to define the role of these drugs in asthma management, and this review should be updated as results from future trials emerge. Studies assessing the role of LAMA add-on should be longer and include a double-ICS treatment arm so that the results can be interpreted in the context of the guideline-recommended treatment options that are available to physicians.

Plain-language summary: Two people looked for published and unpublished research in several databases and websites to find relevant studies comparing LAMA plus ICS with increased doses of ICS for asthma in adults. We analysed the results available up to April 2015 in this systematic review. What did we find? We found one study involving 210 patients with asthma. The trial compared adding tiotropium (a LAMA) to doubling the dose of beclomethasone (a steroid). In the trial, people taking a combination of the LAMA and ICS were slightly less likely to have an asthma attack needing treatment with oral steroids. Our results suggest that for every 1000 people, 18 fewer in the LAMA group would need these treatments compared to patients treated with an increased dose of ICS. However, there is a relatively wide margin of error in this estimate, and the actual number of patients on LAMA who might need steroids because of an asthma attack could range from 52 fewer to 26 more people per 1000. Similarly, neither option was more clearly beneficial on any of the following measures: asthma attacks resulting in hospitalisation or admission to the emergency department, serious adverse events, control of asthma or quality of life related to asthma. On the other hand, LAMA plus ICS might improve lung function a bit more than increasing ICS dose. We didn't have much confidence in the findings because the one included study only looked at one type of LAMA (tiotropium) for a short period of time (14 weeks).