Opioids for chronic osteoarthritis pain: An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks double‐blind duration

Abstract

Background and Objective This updated systematic review evaluated the efficacy and safety of opioids compared with placebo for chronic osteoarthritis pain. Databases and Data Treatment Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to July 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks double‐blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences or standardized mean differences with 95% confidence intervals. We added two new studies with 397 participants for a total of 22 studies with 8,942 participants. Study duration ranged between 4 and 24 weeks. Studies with a parallel and cross‐over design: Based on very low– to low‐quality evidence, opioids provided no clinically relevant pain relief of 50% or greater and no clinically relevant reduction in disability compared with placebo. There was a clinically relevant harm related to the dropout rate due to adverse events. The frequency of serious adverse events did not differ from placebo. Enriched enrolment randomized withdrawal design: Based on very low– to low‐quality evidence, opioids provided no clinically relevant pain relief of 50% or greater and no clinically relevant reduction in disability compared with placebo. Dropout rates due to adverse events and frequency of serious adverse events did not differ from placebo. Conclusions Tolerability of opioids is low and efficacy is not clinically relevant in controlled studies from 4 to 24 weeks for osteoarthritis pain. Significance Within the context of randomized controlled trials (4–24 weeks), opioids provided no clinically relevant pain relief and no clinically relevant reduction in disability compared with placebo in chronic osteoarthritis pain (hip, knee). Number needed to treat for an additional dropout due to side effects was 5 (95% confidence interval 4–7). Two studies found no signals of abuse and addiction. The frequency of serious adverse events including deaths did not differ from placebo.

The Burden of Pain Associated with Osteoarthritis in the Hip or Knee from the Patient’s Perspective: A Multinational Cross-Sectional Study

“…Treatment dissatisfaction with opioids may be related to the toxicity and low efficacy in OA that are well-recognized issues associated with this drug class. These results are consistent with those from RCTs showing that opioids provide limited benefit to patients with OA pain [11][12][13][14] and support the recently updated OARSI and ACR/AF guidelines, which strongly recommend against the use of opioids for managing OA pain [18,19].…”

“…However, use of opioids to manage OA pain remains controversial. Results from randomized controlled trials (RCTs) demonstrated that opioids provide few benefits relative to other analgesics for relieving OA pain [11][12][13][14]. Furthermore, opioids are associated with a number of safety concerns, including toxicities and the risk of abuse and dependency [15][16][17].…”

European* clinical practice recommendations on opioids for chronic noncancer pain – Part 1: Role of opioids in the management of chronic noncancer pain

“…There is low to very low quality GRADE evidence from 22 RCTs of 4-26 weeks with 8,942 participants that opioids are superior in reducing pain and disability, inferior in tolerability and not different in safety compared to placebo for OA-pain (Welsch et al, 2020).…”

Long-term opioid therapy for chronic noncancer pain: second update of the German guidelines

“…The results of the respective meta-analyses for CLBP, 33 osteoarthritis pain, 43 and neuropathic pain, 40 and open-label extension studies of these RCTs 3 were used for evidence-based recommendations for potential indications for opioids. The following primary outcomes were analysed: pain relief of 50% or greater, patient global impression to be much or very much improved, disability, dropout rates to adverse events (tolerability), frequency of serious adverse events, and death.…”