Efficacy, safety, and dose‐dependence of the analgesic effects of opioid therapy for people with osteoarthritis: systematic review and meta‐analysis

Abstract

steoarthritis affects more than 500 million people around the world, and it is a leading cause of disability. 1 Non-pharmacological strategies, such as exercise and maintaining a healthy weight, are recommended for first line management, as are simple analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen). 2 However, advice on using opioid analgesics to treat the pain of knee and hip osteoarthritis is inconsistent; 3,4 opioids are often prescribed, including for about 40% of people with knee osteoarthritis in the United States. 5 Systematic reviews of placebo-controlled trials of the effectiveness of opioids for treating osteoarthritis pain have been limited in scope. For example, one evaluated only opioid treatments of at least four weeks' duration, 6 while a second was restricted to oral opioid therapy. 7 GRADE ratings were not always reported in the abstract or conclusions, and the validity of opioid dose-response analyses were sometimes unclear. 8 One review excluded tramadol because it had been examined in a separate review. 9 We therefore undertook a systematic review to provide a comprehensive evaluation of the efficacy and safety of opioid analgesic therapy regimens for people with osteoarthritis, and to explore dose-effect relationships. MethodsWe searched MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, the Allied and Complementary Medicine Database (AMED), the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL) for eligible randomised controlled trials (RCTs) published in any language in peer-reviewed journals to 31 October 2020 (Supporting Information, table 1). To avoid overestimating treatment effects, 10 we also searched the World Health Organization International Clinical Trials Registry (https://trial search.who.int) for unpublished trials. We screened the reference lists of retrieved publications to identify further RCTs. Our systematic review was prospectively registered with PROSPERO (CRD420191142813; 16 October 2019). Inclusion criteriaWe included RCTs in which the analgesic effect of an opioid was compared with that of placebo in people with osteoarthritis of any type (knee, hip, hand, spine) of any duration. All single ingredient and combination opioid-containing analgesic regimens were included, regardless of opioid dose and administration route. We did not include trials in which the effect of opioid therapy was compared with other treatments but not with placebo. Trials including a range of pain conditions were eligible if data for participants with osteoarthritis could be extracted. Study selectionThree authors (CAS, WA, GZ) independently screened the titles and abstracts and read the full text of potentially eligible publications; disagreements were resolved by consensus.

Efficacy of prescribed opioids for acute pain after being discharged from the emergency department: A systematic review and meta‐analysis

“…However, another systematic review on osteoarthritis not limited to the knee found that opioids may provide a small benefit in pain and disability but may also increase the risk of adverse events. As they did not encounter a study using codeine, their results are comparable to our sensitivity analysis excluding codeine 53 . Moreover, a systematic review on postoperative pain demonstrated that codeine provides less pain relief and more adverse events than NSAIDs 19 .…”

“…As they did not encounter a study using codeine, their results are comparable to our sensitivity analysis excluding codeine. 53 Moreover, a systematic review on postoperative pain demonstrated that codeine provides less pain relief and more adverse events than NSAIDs. 19 Another study, evaluating codeine/acetaminophen and oxycodone/acetaminophen combinations on the first day after ED discharge, demonstrated a not statistically significant trend in more pain relief with oxycodone/acetaminophen (66% vs. 61%).…”

Overview of Anti-Inflammatory and Anti-Nociceptive Effects of Polyphenols to Halt Osteoarthritis: From Preclinical Studies to New Clinical Insights

“…Conversely, topical forms of NSAIDs may offer an alternative solution to relieve OA pain by overcoming the issues correlated to oral formulations; however, they only provide pain relief in patients with mild-to-moderate OA [ 74 ] and are recommended as an initial option, particularly for elderly patients [ 75 ]. Oral opioid administration is an option with limited application, not only due to its prolonged use often leading to physical dependence, but also because it exerts only minimal relief of OA symptoms within 12 weeks, as demonstrated by a recent meta-analysis of randomized controlled trials on patients with knee and/or hip OA [ 76 , 77 ]. Due to the localized nature of OA, injectable preparations are an attractive treatment approach to: (1) provide mechanical stability and lubricating mechanisms in the synovial fluid; (2) exert a direct effect on inflammation, oxidation and proteases production [ 78 , 79 ]; (3) mediate IA drug injection, minimizing side effects.…”

Analgesics in rheumatic diseases – a necessary component of therapy aimed at improving the quality of life

“…В недавно опубликованном систематическом обзоре и метаанализе рандомизированных плацебо-контролируемых исследований подтвержден незначительный анальгетический потенциал опиоидов при ОА [40]. Так, в 19 РКИ (n=8965) разность средних (mean difference, MD) по боли составила -4,59 балла (из 100 возможных), 95% ДИ -от -7,17 до -2,02.…”