Short‐term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: A meta‐analysis of randomised placebo‐controlled trials

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Abstract
Pain is the most debilitating symptom in osteoarthritis of the knee (OAK). To determine the short-term pain-relieving effects of seven commonly used pharmacological agents for OAK pain by performing a systematic review of randomised placebo-controlled trials. In total, 14,060 patients in 63 trials were evaluated. Opioids and oral NSAIDs therapy in patients with moderate to severe pain (mean baseline 64.3 and 72.8 mm on VAS respectively) had maximum efficacies compared to placebo at 2-4 weeks of 10.5 mm [95% CI: 7.4-13.7] and 10.2 mm [95% CI: 8.8-11.2] respectively. The efficacy of opioids may be inflated by high withdrawal rates (24-50%) and "best-case" scenarios reported in intention-to-treat analyses. In patients with moderate pain scores on VAS (mean range from 51 to 57 mm), intra-articular steroid injections and topical NSAIDs had maximum efficacies at 1-3 weeks of 14.5mm [95% CI: 9.7-19.2] and 11.6 mm [95% CI: 7.4-15.7], respectively. Paracetamol, glucosamin sulphate and chondroitin sulphate had maximum mean efficacies at 1-4 weeks of only 4.7 mm or lower. Heterogeneity tests revealed that best efficacy values of topical NSAIDs may be slightly deflated, while data for oral NSAIDs may be slightly inflated due to probable patient selection bias. Clinical effects from pharmacological interventions in OAK are small and limited to the first 2-3 weeks after start of treatment. The pain-relieving effects over placebo in OAK are smaller than the patient-reported thresholds for relevant improvement.