Efficacy and harms of long‐term opioid therapy in chronic non‐cancer pain: Systematic review and meta‐analysis of open‐label extension trials with a study duration ≥26 weeks

European Journal of Pain

Klose

Welsch

et al. 2019

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Background and Objective This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in non‐malignant chronic low back pain. Databases and Data Treatment Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to May 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks of 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. We added nine new studies with 2,980 participants for a total of 21 studies with 7,650 participants. Study duration ranged between 4 and 15 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, but a clinically relevant reduction of disability compared to placebo. Enriched enrolment randomized withdrawal (EERW) design: Based on very low to low‐quality evidence, opioids provided a clinically relevant pain relief of 50% or greater, but not a clinically relevant reduction of disability compared to placebo. There was no clinically relevant harm with regard to serious adverse events by opioids compared to placebo in studies with parallel/cross‐over and EERW design. There was a relevant harm with regard to drop out rates due to adverse events in studies with parallel/cross‐over, but not in studies with EERW design. Conclusions Opioids may provide a safe and clinically relevant pain relief for 4–15 weeks in highly selected patients. Significance Within the context of randomized controlled trials of 4–15 weeks, opioids provided a clinically relevant pain relief of 30% or greater and a clinically relevant reduction of disability compared to placebo in non‐malignant chronic low back pain. Number needed to treat for an additional drop out due to side effects was 11 (95% confidence interval: 6–33). Assessment of abuse and addiction was incomplete. The frequency of serious adverse events including deaths did not differ from placebo.

Section: Discussionmentioning

confidence: 99%

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

European Journal of Pain

Klose

Welsch

et al. 2019

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“…The European Medicines Agency recommends open-label extension studies to assess long-term efficacy and safety (European Medicines Agency, 2017). The results of a systematic review of open-label extension studies will be published in another paper (Bialas, Maier, Klose, & Häuser, 2019).…”

Section: Overall Completeness and Applicability Of Evidencementioning

confidence: 99%

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

Welsch

European Journal of Pain

Klose

et al. 2020

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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 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.…”

Section: Methodsmentioning

confidence: 99%

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

Bock²,

Hüppe

et al. 2020

PR9

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