Pain Management in Rheumatoid Arthritis Save

BMC has published a full read literture review of pharmacological pain management in rheumatoid arthritis, pointing out that the best evidence for pain control comes from the use of DMARDs and treat-to-target strategies.  In contrast, there is widespread use of analgesics in RA, although the evidence supporting their use is often lacking.  More research in the area of pain management in RA is needed. 

Information covered is based on 13 systematic reviews of drug efficacy for pain in RA. Overall there was moderate- to high-quality evidence supporting synthetic DMARDs and biological/targeted synthetic DMARDs in RA pain control (relative to placebo). Older trials (1960s–1990s) regarding the use of opioids, paracetamol, NSAIDs, sould only show low-quality evidence for pain control. Lastly there was no supportive evidence for gabapentinoids, or long-term opioids. There were 21 studies of analgesic prescribing in RA, showing substantial and sustained use of analgesics, particularly opioids, with approximately one quarter and > 40% of patients receiving chronic opioid prescriptions in England and North America.

Key points on several pain-relieving modalities:

• Acetaminophen/paracetamol:  Most were short-term trials, using atypical dosing (doses ranging 650 mg to 7.5 g/day). Pain relief was small, sometimes significant, when compared to placebo.  Compared to NSAIDs or weak opioids, with no differences in efficacy was often seen. Mixed results were seen comparing paracetamol with NSAIDs vs. NSAIDs. 
• Opioids: Cochrane review summarised 11 trials, and while many of these studies showed significant benefit in at least one measure; these trials are severely limited by short duration, high bias, and low quality evidence. While weak oral opioids may be effective for some, adverse effects may offset benefits, with insufficient evidence to draw conclusions on opioids for > 6 weeks or strong opioids.
• NSAIDs: network meta-analysis evaluated NSAID efficacy from 21 trials of various NSAIDs. Naproxen (1000 mg/day) associated with a statistically significant greater reduction in pain vs. placebo, although evidence was considered “very low” quality. No other NSAIDs had significant differences in their effects on pain vs. placebo. Many trials were biased in favor of those likely to benefit from NSAIDs as trial design required patients to have been taking an NSAID pre-trial, and have flared on stopping it as they were randomized and treated. 
• Anti-depressants: Despite a Cochrane review of 8 trials (7/8 w/ high-risk of bias) they foundmixed results from their meta-analysis. There was no evidence of an effect of antidepressants on pain in the short term (< 1 week), and conflicting evidence of a medium- (1–6 weeks) or long-term (> 6 weeks) benefit.
• Cannabinoids:  not well studied in RA; and when studied only on small sample size. When a positive analgesic effect was reported it was often confounded by higher adverse event rates with cannabinoids - with more  dizziness (26% vs. 4%) and light-headedness (10% vs 4%).
• Glucocorticoids: metanalyses of 14 “high-quality” studies showed greatest benefit on pain visual analogue scale (VAS) at 0 to 3 months, with less effect by > 3 to 6 months. Systemic glucocorticoids may be “analgesic in RA” with benefits greatest shortly after initiation.

Systematic reviews show moderate- to high-quality trial evidence (from more contemporary time-periods) short-term systemic glucocorticoids and synthetic, biologic, and targeted synthetic DMARDs have efficacy at reducing pain relative to placebo.  No trials have evaluated gabapentinoids, serotonin and norepinephrine reuptake inhibitors, or long-term opioids.