Efficacy and safety of multiple doses of Revefenacin for therapy in patients with moderate to severe chronic obstructive pulmonary disease in stable period: a meta-analysis

OBJECTIVE To systematically evaluate the efficacy and safety of multiple doses of revefenacin(22, 44, 88, 175, 350, 700 μg) in patients with moderate to severe chronic obstructive pulmonary disease(COPD) in stable period.METHODS literature searching was performed via Medline/PubMed, Cochrane Library, Embase, Web of Science, VIP, CNKI, WanFang databases from their inception to June 2020, and searched ClinicalTrials.gov to obtain unpublished data. The randomized controlled trials(RCTs) compared efficacy and safety of revefenacin versus placebo in patients with moderate to severe COPD in stable period were included. The risk of bias was assessed via Cochrane risk of bias assessment tool after data extracted from clinical studies which met the inclusion criteria and the meta-analysis was performed by using RevMan 5.3 software.RESULTS Five RCTs with 1 927 participates were enrolled. The meta-anlysis showed that revefenacin was superior to placebo in terms of change in FEV1total: MD=0.11, 95%CI(0.09, 0.13), P<0.000 01; 22 μg: MD=0.05, 95%CI(0.00, 0.10), P=0.04; 44 μg: MD=0.05, 95%CI(0.01, 0.10), P=0.01; 88 μg: MD=0.12, 95%CI(0.07, 0.18)，P<0.000 01; 175 μg: MD=0.13, 95%CI(0.11, 0.16), P<0.000 01; 350 μg: MD=0.1, 95%CI(0.05, 0.20), P=0.000 7; 700 μg: MD=0.08, 95%CI(0.03, 0.13), P=0.002 and the proportion of patients whose SGQR scores dropped by four or more unitstotal: RR=1.29, 95%CI(1.12, 1.49), P=0.000 4; 88 μg: RR=1.29, 95%CI(1.06,1.58), P=0.01; 175 μg: RR=1.29, 95%CI(1.06, 1.58), P=0.01 with a significant difference. The incidence of dyspnea in Revefenain group was significantly lower than that in placebo group(P=0.005), and the incidence of back pain was significantly higher than that in placebo group(P=0.006). In a direct comparison between 88 μg and 175 μg, there was no significant difference in the incidence of total adverse reactions, serious adverse events, and common adverse events(headache, cough, back pain, sore throat, dyspnea, upper respiratory tract infection) compared with placebo.CONCLUSION Revefenacin shows better efficacy and tolerance in patients with moderate to severe COPD in stable period, and 175 μg did not exhibit its advantage over 88 μg, both 88 μg and 175 μg may become alternative options for the clinical treatment of moderate to severe COPD in stable period.