Non-steroidal anti-inflammatory drugs for acute gout.
Gout is an inflammatory arthritis resulting from the deposition of monosodium urate crystals in and around joints. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat acute gout. This is an update of a Cochrane Review first published in 2014.
To assess the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) (including cyclo-oxygenase-2 (COX-2) inhibitors (COXIBs)) for acute gout.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase for studies to 28 August 2020. We applied no date or language restrictions.
We considered randomised controlled trials (RCTs) and quasi-RCTs comparing NSAIDs with placebo or another therapy for acute gout. Major outcomes were pain, inflammation, function, participant-reported global assessment, quality of life, withdrawals due to adverse events, and total adverse events.
We used standard methodological procedures as expected by Cochrane.
We included in this update 28 trials (3406 participants), including 5 new trials. One trial (30 participants) compared NSAIDs to placebo, 6 (1244 participants) compared non-selective NSAIDs to selective cyclo-oxygenase-2 (COX-2) inhibitors (COXIBs), 5 (712 participants) compared NSAIDs to glucocorticoids, 13 compared one NSAID to another NSAID (633 participants), and single trials compared NSAIDs to rilonacept (225 participants), acupuncture (163 participants), and colchicine (399 participants). Most trials were at risk of selection, performance, and detection biases. We report numerical data for the primary comparison NSAIDs versus placebo and brief results for the two comparisons - NSAIDs versus COX-2 inhibitors and NSAIDs versus glucocorticoids. Low-certainty evidence (downgraded for bias and imprecision) from 1 trial (30 participants) shows NSAIDs compared to placebo. More participants (11/15) may have a 50% reduction in pain at 24 hours with NSAIDs than with placebo (4/15) (risk ratio (RR) 2.7, 95% confidence interval (CI) 1.1 to 6.7), with absolute improvement of 47% (3.5% more to 152.5% more). NSAIDs may have little to no effect on inflammation (swelling) after four days (13/15 participants taking NSAIDs versus 12/15 participants taking placebo; RR 1.1, 95% CI 0.8 to 1.5), with absolute improvement of 6.4% (16.8% fewer to 39.2% more). There may be little to no difference in function (4-point scale; 1 = complete resolution) at 24 hours (4/15 participants taking NSAIDs versus 1/15 participants taking placebo; RR 4.0, 95% CI 0.5 to 31.7), with absolute improvement of 20% (3.3% fewer to 204.9% more). NSAIDs may result in little to no difference in withdrawals due to adverse events (0 events in both groups) or in total adverse events; two adverse events (nausea and polyuria) were reported in the placebo group (RR 0.2, 95% CI 0.0, 3.8), with absolute difference of 10.7% more (13.2% fewer to 38% more). Treatment success and health-related quality of life were not measured. Moderate-certainty evidence (downgraded for bias) from 6 trials (1244 participants) shows non-selective NSAIDs compared to selective COX-2 inhibitors (COXIBs). Non-selective NSAIDs probably result in little to no difference in pain (mean difference (MD) 0.03, 95% CI 0.07 lower to 0.14 higher), swelling (MD 0.08, 95% CI 0.07 lower to 0.22 higher), treatment success (MD 0.08, 95% CI 0.04 lower to 0.2 higher), or quality of life (MD -0.2, 95% CI -6.7 to 6.3) compared to COXIBs. Low-certainty evidence (downgraded for bias and imprecision) suggests no difference in function (MD 0.04, 95% CI -0.17 to 0.25) between groups. Non-selective NSAIDs probably increase withdrawals due to adverse events (RR 2.3, 95% CI 1.3 to 4.1) and total adverse events (mainly gastrointestinal) (RR 1.9, 95% CI 1.4 to 2.8). Moderate-certainty evidence (downgraded for bias) based on 5 trials (712 participants) shows NSAIDs compared to glucocorticoids. NSAIDs probably result in little to no difference in pain (MD 0.1, 95% CI -2.7 to 3.0), inflammation (MD 0.3, 95% CI 0.07 to 0.6), function (MD -0.2, 95% CI -2.2 to 1.8), or treatment success (RR 0.9, 95% CI 0.7 to 1.2). There was no difference in withdrawals due to adverse events with NSAIDs compared to glucocorticoids (RR 2.8, 95% CI 0.5 to 14.2). There was a decrease in total adverse events with glucocorticoids compared to NSAIDs (RR 1.6, 95% CI 1.0 to 2.5).
Low-certainty evidence from 1 placebo-controlled trial suggests that NSAIDs may improve pain at 24 hours and may have little to no effect on function, inflammation, or adverse events for treatment of acute gout. Moderate-certainty evidence shows that COXIBs and non-selective NSAIDs are probably equally beneficial with regards to improvement in pain, function, inflammation, and treatment success, although non-selective NSAIDs probably increase withdrawals due to adverse events and total adverse events. Moderate-certainty evidence shows that systemic glucocorticoids and NSAIDs probably are equally beneficial in terms of pain relief, improvement in function, and treatment success. Withdrawals due to adverse events were also similar between groups, but NSAIDs probably result in more total adverse events. Low-certainty evidence suggests no difference in inflammation between groups. Only low-certainty evidence was available for the comparisons NSAID versus rilonacept and NSAID versus acupuncture from single trials, or one NSAID versus another NSAID, which also included many NSAIDs that are no longer in clinical use. Although these data were insufficient to support firm conclusions, they do not conflict with clinical guideline recommendations based upon evidence from observational studies, findings for other inflammatory arthritis, and expert consensus, all of which support the use of NSAIDs for acute gout.
van Durme CM
，Wechalekar MD
，Landewé RB
，Pardo Pardo J
，Cyril S
，van der Heijde D
，Buchbinder R
... -
《Cochrane Database of Systematic Reviews》
Colchicine for acute gout.
This is an updated Cochrane Review, first published in 2006 and updated in 2014. Gout is one of the most common rheumatic diseases worldwide. Despite the use of colchicine as one of the first-line therapies for the treatment of acute gout, evidence for its benefits and harms is relatively limited.
To update the available evidence of the benefits and harms of colchicine for the treatment of acute gout.
We updated the search of CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and WHO ICTRP registries to 28 August 2020. We did not impose any date or language restrictions in the search.
We considered published randomised controlled trials (RCTs) and quasi-randomised controlled trials (quasi-RCTs) evaluating colchicine therapy compared with another therapy (placebo or active) in acute gout; low-dose colchicine at clinically relevant doses compared with placebo was the primary comparison. The major outcomes were pain, participant global assessment of treatment success (proportion with 50% or greater decrease in pain from baseline up to 32 to 36 hours), reduction of inflammation, function of target joint, serious adverse events, total adverse events and withdrawals due to adverse events.
We used standard methodological procedures as expected by Cochrane in this review update.
We included four trials (803 randomised participants), including two new trials, in this updated review. One three-arm trial compared high-dose colchicine (52 participants), low-dose colchicine (74 participants) and placebo (59 participants); one trial compared high-dose colchicine with placebo (43 participants); one trial compared low-dose colchicine with non-steroidal anti-inflammatory drugs (NSAIDs) (399 participants); and one trial compared low-dose colchicine with Chuanhu anti-gout mixture (traditional Chinese Medicine compound) (176 participants). We did not identify any trials comparing colchicine to glucocorticoids (by any route). The mean age of participants ranged from 51.2 to 70 years, and trial duration from 48 hours to 12 weeks. Two trials were at low risk of bias, one was possibly susceptible to selection bias (random sequence generation), reporting bias and other bias, and one open-label trial was at high risk of performance and detection bias. For the primary comparison, low-quality evidence from one trial (103 participants, downgraded for imprecision and bias) suggests low-dose colchicine may improve treatment outcome compared to placebo with little or no increased risk of adverse events. The number of people who reported treatment success (50% or greater pain reduction) at 32 to 36 hours was slightly larger with low-dose colchicine (418 per 1000) compared with placebo (172 per 1000; risk ratio (RR) 2.43, 95% confidence interval (CI) 1.05 to 5.64; absolute improvement 25% more reported success (7% more to 42% more, the 95% CIs include both a clinically important and unimportant benefit); relative change of 143% more people reported treatment success (5% more to 464% more). The incidence of total adverse events was 364 per 1000 with low-dose colchicine compared with 276 per 1000 with placebo: RR 1.32, 95% CI 0.68 to 2.56; absolute difference 9% more events with low-dose colchicine (9% fewer to 43% more, the 95% CIs include both a clinically important effect and no effect); relative change of 32% more events (32% fewer to 156% more). No participants withdrew due to adverse events or reported any serious adverse events. Pain, inflammation and function were not reported. Low-quality evidence (downgraded for imprecision and bias) from two trials (124 participants) suggests that high-dose colchicine compared to placebo may improve symptoms, but with increased risk of harms. More participants reported treatment success at 32 to 36 hours with high-dose colchicine (518 per 1000) compared with placebo (240 per 1000): RR 2.16, 95% CI 1.28 to 3.65, absolute improvement 28% (8% more to 46% more); more also had reduced inflammation at this time point with high-dose colchicine (504 per 1000) compared with placebo (48 per 1000): RR 10.50, 95% CI 1.48 to 74.38; absolute improvement 45% greater (22% greater to 68% greater); but more adverse events were reported with high-dose colchicine (829 per 1000 compared with 260 per 1000): RR 3.21, 95% CI 2.01 to 5.11, absolute difference 57% (26% more to 74% more). Pain and function were not reported. Low-quality evidence from a single trial comparing high-dose to low-dose colchicine indicates there may be little or no difference in benefit in terms of treatment success at 32 to 36 hours but more adverse events associated with the higher dose. Similarly, low-quality evidence from a single trial indicates there may also be little or no benefit of low-dose colchicine over NSAIDs in terms of treatment success and pain reduction at seven days, with a similar number of adverse events reported at four weeks follow-up. Reduction of inflammation, function of target joint and withdrawals due to adverse events were not reported in either of these trials, and pain was not reported in the high-dose versus low-dose colchicine trial. We were unable to estimate the risk of serious adverse events for most comparisons as there were few events reported in the trials. One trial (399 participants) reported three serious adverse (one in a participant receiving low-dose colchicine and two in participants receiving NSAIDs), due to reasons unrelated to the trial (low-quality evidence downgraded for bias and imprecision).
We found low-quality evidence that low-dose colchicine may be an effective treatment for acute gout when compared to placebo and low-quality evidence that its benefits may be similar to NSAIDs. We downgraded the evidence for bias and imprecision. While both high- and low-dose colchicine improve pain when compared to placebo, low-quality evidence suggests that high-dose (but not low-dose) colchicine may increase the number of adverse events compared to placebo, while low-quality evidence indicates that the number of adverse events may be similar with low-dose colchicine and NSAIDs. Further trials comparing colchicine to placebo or other treatment will likely have an important impact on our confidence in the effect estimates and may change the conclusions of this review. There are no trials reporting the effect of colchicine in populations with comorbidities or in comparison with other commonly used treatments, such as glucocorticoids.
McKenzie BJ
，Wechalekar MD
，Johnston RV
，Schlesinger N
，Buchbinder R
... -
《Cochrane Database of Systematic Reviews》
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