Effects of Roflumilast on Patients with Chronic Obstructive Pulmonary Disease Treated with Inhaled Corticosteroid/Long-Acting β2 Agonist: A Meta-analysis

OBJECTIVE: Roflumilast is a novel therapeutic drug for chronic obstructive pulmonary disease (COPD). This study was designed to evaluate the efficacy and safety of roflumilast combining inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) in treating COPD patients through the meta-analysis. METHODS: Randomized controlled trials of roflumilast combining ICS/LABA in treating patients with severe and profound COPD were searched from PubMed, Cochrane Library, and Embase databases from their establishment to February 2022. The quality of included studies was assessed by Cochrane risk bias assessment tool. The main outcomes of these studies should include at least one of the following clinical outcome indicators: forced expiratory volume in one second (FEV(1)), exacerbation rate, and adverse events (AEs) such as diarrhea, nasopharyngitis, and headache. RESULTS: Six articles were included in the study, including 9,715 patients. Meta-analysis revealed that compared with placebo, roflumilast gained superiority for severe COPD patients treated with ICS/LABA combinations in FEV(1) before bronchodilator administration (MD = 46.62, 95% CI (30.69, 62.55), P < 0.00001), FEV(1) after bronchodilator administration (MD = 45.62, 95% CI (34.95, 56.28), P < 0.00001), and COPD exacerbation rate (RR = 0.90, 95% CI (0.87, 0.94), P = 0.001). In terms of safety, the incidence of diarrhea, headache, nausea, weight loss, back pain, loss of appetite, and insomnia was notably higher in the roflumilast group than in the placebo group. CONCLUSION: Roflumilast is suggested to be significantly effective for severe COPD patients with ICS/LABA combination therapy, which reduces the exacerbation rate but also leads to PDE4 inhibitor-related adverse reactions.