Efficacy and safety of extended-release oral opioid for cough in idiopathic pulmonary fibrosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Patients with idiopathic pulmonary fibrosis (IPF) experience a high burden of cough. Currently, no established effective therapy exists for cough in IPF. The overall evidence base of oral extended-release (ER) opioid therapies in this population remains limited. This study aimed to compare the efficacy and safety of ER oral opioids versus placebo for cough in patients with IPF. METHODS: PubMed, Embase, Cochrane, and ClinicalTrial.gov databases were reviewed for randomized controlled trials (RCTs). The primary outcome was 24-hour objective cough frequency. Secondary outcomes included Evaluating Respiratory Symptoms-Idiopathic Pulmonary Fibrosis (E-RS IPF) cough subscale score, Cough Severity-Numeric Rating Scale (CS-NRS) score. Safety outcomes included serious adverse events and adverse events leading to discontinuation. RESULTS: Three RCTs, including 250 patients, were analyzed. Opioid interventions included ER nalbuphine and morphine. ER opioid statistically significantly improved 24-hour objective cough frequency (GMR 0.46; 95% CI 0.23 to 0.92; p = 0.029), CS-NRS score (MD -1.69; 95% CI -2.55 to -0.84; p < 0.001), and E-RS IPF cough subscale score (MD -0.49; 95% CI -0.89 to -0.09; p = 0.016), compared with placebo. No statistically significant differences were observed for serious adverse events or adverse events leading to discontinuation. CONCLUSIONS: ER oral opioids significantly improved cough frequency and patient-reported cough severity and discomfort in patients with IPF, without a significant increase in serious adverse events or treatment discontinuation. Extended-release opioids may be cautiously considered as a therapeutic option for cough in patients with IPF.