LAUSR

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 31 January 2022. Eligibility criteria for study selection were 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 (DRAEs) were meta-analytically evaluated using the Review Manager Software version 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 PRI and 169 placebo, each as monotherapy) proved to be suitable for quantitative and qualitative analysis. Treatment with PRI 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 < .00001; Cohen´s h: 0.506, NNT: 4.1; Chi2 for heterogeneity 1.41 (p = .24], I 2  = 29%), and significantly higher response rates were also found for all secondary efficacy endpoints. The safety of PRI 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 = .54, NNH: 62.6), and related discontinuations were reported for four vs. one patient (2.3 vs. 0.6%; p = .231). Conclusions 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 PRI 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. PLAIN LANGUAGE SUMMARY Muscle pain is one of the most common pain problems worldwide. In the majority of cases, muscle pain is temporary, transient, and benign in nature. However, people affected may still experience severe pain and significant pain-related disabilities in daily life activities that may require temporary drug treatment – also in order to be able to undertake the non-drug treatment measures necessary to prevent recurrence. Current treatment recommendations for muscle pain are largely ´non-specific´ and limited to symptomatic pain-relieving measures (e.g. non-steroidal anti-inflammatories), while muscle relaxants – such as pridinol (PRI), which has been reapproved in Germany in 2017 and first time approved in the United Kingdom, Spain, and Poland in 2020 – are currently not recommended (primarily due to insufficient efficacy data from controlled clinical trials) but nevertheless frequently prescribed. Due to our systematic literature research of double-blind randomized and placebo-controlled trials, a 3-week monotherapy with PRI vs. placebo proved to be comparably tolerated, but significantly more effective in patients with muscle pain – irrespective of the mode of administration (oral or as intramuscular injection). These outcomes confirm already available real-world evidence on the beneficial efficacy and tolerability of PRI in daily practice. However, more recent RCTs or numerically larger comparative real-world evidence analyses are needed to evaluate the efficacy of PRI in comparison to currently recommended first-line therapies for patients with muscle pain.