Efficacy and safety/tolerability of pridinol: a meta-analysis of double-blind, randomized, placebo-controlled trials in adult patients with muscle pain

Abstract

Objective To evaluate analgesic efficacy and safety/tolerability of the nonbenzodiazepine antispasmodic pridinol (PRI) in patients with muscle-related pain. Methods Systematic review and meta-analysis of randomized placebo-controlled trials (RCTs) according to PRISMA guidelines and Cochrane recommendations. Data sources included Google Scholar, Embase, PubMed, ClinicalTrials.gov, EU Clinical Trials Registry, Chinese Clinical Trial Registry, UMIN Clinical Trials Registry, and product manufacturer archives from inception to January 31st, 2022. Eligibility criteria for study selection was randomized, placebo-controlled trials with PRI in adults (≥18 years) with muscle-related pain. Data extraction, synthesis, and analysis carried out by two reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Categorial global response rates (number of patients) based on clinical judgement of study physicians (as primary efficacy endpoint), and response on pain at rest, pain at movement, stiffness, tenderness, and movement restriction (as secondary efficacy endpoints), as well as the number of patients with drug-related adverse events were meta-analytically evaluated using the Review Manager Software 5.4.1. Results In total, 38 records were identified, but only two placebo-controlled studies [with 342 patients with mild to moderate acute muscle pain (55.3% female, age 50.6 ± 16.6 years), of whom 173 received pridinol and 169 placebo, each as monotherapy] proved to be suitable for quantitative and qualitative analysis. Treatment with pridinol was (irrespective of its mode of administration as oral tablet or intramuscular injection) associated with a significantly higher global response rate compared to placebo (74.0 vs. 49.7%; OR 2.86, 95%-CI: 1.82-4.51; p < 0.00001; Cohen´s h: 0.506, NNT: 4.1; Chi 2 for heterogeneity 1.41 [p = 0.24], I2=29%), and significantly higher response rates were also found for all secondary efficacy endpoints. The safety of pridinol was comparable to that of placebo: DRAEs were only seen in one of the two studies and reported for 13 vs. 10 patients (OR: 0.76 95%-CI: 0.32-18.1; p = 0.54, NNH: 62.6), and related discontinuations were reported for four vs. one patient (2.3 vs. 0.6%; p = 0.231). Conclusion The results from this meta-analysis as based on two placebo-controlled studies in adult patients with mild to moderate acute muscle pain demonstrate that a 3-week monotherapy with pridinol showed a comparable safety profile, but significantly better analgesic effects and improvements of related impairments such as stiffness, tenderness and movement restrictions compared with placebo – irrespective of its mode of administration.