Efficacy of Revefenacin in treatment of moderate-to-very-severe Chronic Obstructive Pulmonary Disease: a systematic review and meta-analysis

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major global health issue responsible for 5% of global deaths each year, and novel treatments are at a premium. Long acting-muscarinic antagonists are a standard treatment for COPD, and the recent approval of Revefenacin, a novel, once-daily, nebulized LAMA, prompts a need for a systematic review and meta-analysis of results. OBJECTIVES: To assess the efficacy of Revefenacin, a novel, once-daily, nebulized LAMA in the treatment of moderate to very severe COPD. DATA SOURCES: MEDLINE (OVID), EMBASE, and CINAHL databases, as well as grey literature sources Clinicaltrials.gov and the International Clinical Trials Registry Portal. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: No age, geographical, contextual or other restrictions were imposed on populations. All human subjects diagnosed with moderate to severe Chronic Obstructive Pulmonary Disease (COPD) were eligible. Intervention: a novel bronchodilator (Revefenacin). Comparator: Placebo. Outcomes: the efficacy of Revefenacin, measured as the endpoint change in trough FEV1 from baseline. Study design: Randomised Controlled Trials (RCTs). Only studies written in English were considered. STUDY APPRAISAL AND SYNTHESIS METHODS: 1571 records were initially screened, with 27 being eligible for full text review. Eventually, 12 articles for 7 trials were included. A random-effects meta-analysis was conducted with the primary outcome of difference in means for change in trough FEV1 from baseline to study endpoint. RESULTS: 1472 patients were analysed, and the overall difference in means was an increase of 119.073 mL in change in trough FEV1 from baseline to study endpoint for the Revefenacin group compared to the placebo. This result was statistically significant, with a 95% confidence interval of 102.254 mL to 135.893 mL. LIMITATIONS: Limitations of the study include possible risk of publication bias and placebo as the only comparator, relatively few trials (7), and a low generalizability of findings due to the specific nature of RCT populations excluding multi-morbid, and other complicated patients. CONCLUSIONS: Revefenacin is an efficacious intervention when compared to placebo in the treatment of moderate to very severe COPD. Further research is needed in order to assess its efficacy compared to current standard of care, through RCTs or network meta-analysis. What is known: - Existing COPD treatments aim to relief symptoms and improve quality of life. - Revefenacin a novel bronchodilator, was approved in 2018 by the US FDA. - Mong-acting muscarinic antagonists are often used in the management of COPD symptoms. What this study adds: - Revefenacin is a novel drug and no systematic review has been conducted on its efficacy. - The meta-analysis utilised a novel method which accounts for the unit-of-analysis error, when comparing multi- arms studies to a single placebo group (technique of exact adjustment.