The Role of Long-Acting Muscarinic Antagonists in Combination with Inhaled Corticosteroids in Uncontrolled Persistent Asthma

Although long-acting muscarinic antagonists (LAMA) are approved for the maintenance treatment of asthma, it is difficult to obtain the body of evidence in clinical settings. A systematic review evaluating the use of LAMA as an add-on therapy to inhaled corticosteroids was published in 2018 by Sobieraj et al. A critical appraisal of this systematic review by using AMSTAR 2 pointed out some of its limitations, such as improper explanation for exclusion of a study, statistical combination of results, and explanation of heterogeneity. The problem of statistical combination of results was introduced by inappropriate data extraction from crossover trials and exclusion of a study which had used a different effect size or quality of life (QOL) scale. For these reasons, generic inverse variance method as used in a Cochrane systematic review by Kews et al., and standardized mean difference were applied for comparing the efficacy of longacting β2-agonists (LABA) with LAMA as add-on therapy to inhaled corticosteroids. Thereafter, further study results were pooled. We generated a GRADE (Grading of Recommendations, Assessment,Development, and Evaluation) summary of findings to assess the degree of heterogeneity and evaluate the certainty of evidence. Apart from a QOL outcome, our statistical combination had not demonstrated a substantial difference from the existing systematic review by Sobieraj et al. in any treatment outcome. On the other hand, our GRADE summary of findings is more precise and is easy to use by the clinicians for making clinical decisions. An exploratory network meta-analysis was further performed to combine the longstanding evidence regarding the use of LABA and LAMA. The results suggested that a network meta-analysis might be more useful than the existing systematic review by Sobieraj et al. to arrive at a clinical decision for the management of asthma.