Abstract: Eleven studies (672 participants) were included in the review. Four studies assessed the efficacy of single doses of various opioid and non-opioid analgesics; a pooled analysis of these studies was not performed but in each study opioids reduced pain more than placebo. There were no differences between analgesic drugs in these studies. Seven studies were between one and six weeks in duration and assessed six different oral opioids (dextropropoxyphene, codeine, tramadol, tilidine, pentazocine, morphine), either alone or combined with non-opioid analgesics. The only strong opioid investigated was controlled-release morphine sulphate, in a single study with 20 participants. Six studies compared an opioid to placebo. Opioids were superior to placebo in patient-reported global impression of change (3 studies, 324 participants: relative risk (RR) 1.44, 95% CI 1.03 to 2.03) but not for the number of withdrawals due to inadequate analgesia (4 studies, 345 participants: RR 0.82, 95% CI 0.34 to 2.0). Adverse events (most commonly nausea, vomiting, dizziness and constipation) were more frequent in patients receiving opioids compared to placebo (4 studies, 371 participants: odds ratio 3.90, 95% CI 2.31 to 6.56); the pooled risk ratio for withdrawal due to adverse events was 2.67 (3 studies, 331 participants: 95% CI 0.52 to 13.75). One study compared an opioid (codeine with paracetamol) to an NSAID (diclofenac) and found no difference in efficacy or safety between interventions. There is limited evidence that weak oral opioids may be effective analgesics for some patients with RA, but adverse effects are common and may offset the benefits of this class of medications. There is insufficient evidence to draw conclusions regarding the use of weak opioids for longer than six weeks, or the role of strong opioids.

Plain-language summary: There were no studies in people with rheumatoid arthritis that looked at the effects of weak opioids taken for more than six weeks. There were not enough studies of strong opioids to draw conclusions about their effects in rheumatoid arthritis. What is rheumatoid arthritis and what are opioids? When you have rheumatoid arthritis your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff and painful. The small joints of your hands and feet are usually affected first. There is no cure for rheumatoid arthritis at present, so the treatments aim to relieve the pain and stiffness and improve your ability to move. Opioids are powerful pain-relieving substances that range in strength from relatively mild, such as codeine, to strong, such as morphine. Some examples of weak opioids are codeine (for example Panadeine Forte®) and tramadol (for example Tramal). Some examples of strong opioids are oxycodone (for example Percocet, Endone), morphine and fentanyl (for example Duragesic). They can be taken in a pill form, as an injection or as a patch placed on the skin. Common opioid side-effects include nausea, constipation and drowsiness. Best estimate of what happens to people with rheumatoid arthritis who take opioids Patient-reported global impression of change -18 more people out of 100 reported a 'good' or 'very good' improvement in the symptoms of their rheumatoid arthritis after treatment with opioids for between one and six weeks (18% absolute improvement) -57 people out of 100 reported a 'good' or 'very good' improvement in symptoms -40 people out of 100 who took a placebo reported a 'good' or 'very good' improvement in symptoms Side-effects -30 more people out of 100 experienced at least one side-effect during treatment with opioids for between one and six weeks (30% absolute difference) -51 people out of 100 had at least one side-effect -21 people out of 100 who took a placebo had at least one side-effect