Non-steroidal anti-inflammatory drugs (NSAIDs) for acute gout

What is an acute gout flare, and what are NSAIDs?

Gout results from the deposition of monosodium urate crystals within and around joints and presents usually as self-limited episodes of acute arthritis.

NSAIDs (non-steroidal anti-inflammatory drugs) are drugs that reduce pain and inflammation but may increase the risk of gastrointestinal ulcers and bleeding. Cyclo-oxygenase (COX)-2 selective inhibitors (COXIBs) are a subgroup of NSAIDs that lead to fewer stomach ulcers.

Study characteristics

This is an update of a Cochrane Review first published in 2014 and updated on 28 August 2020, which revealed 28 trials (3406 participants). Most participants were men (69% to 100%) aged 44 to 66 years, with acute gout lasting less than 48 hours.

One trial (30 participants) compared placebo to an NSAID, 13 trials (518 participants) compared an NSAID to another NSAID, 6 trials (1244 participants) compared NSAIDs to COXIBs, 5 trials (772 participants) compared glucocorticoids to NSAIDs, 1 trial compared interleukin-1 inhibitors to NSAIDs (225 participants), 1 trial compared acupuncture plus infrared irradiation to NSAIDs (163 participants), and 1 trial compared colchicine to NSAIDs (399 participants). We present key results for the primary comparison, NSAIDs versus placebo, as follows.

Key results

NSAID versus placebo

Pain improvement by more than 50% after 24 hours

47 more people out of 100 who took NSAIDs reported more than 50% improvement in pain compared to those given placebo

- 73 people out of 100 who took NSAIDs reported more than 50% improvement in pain

- 26 people out of 100 who took placebo reported more than 50% improvement in pain

Swelling improvement by more than 50% after 24 hours

6 more people out of 100 who took NSAIDs had more than 50% improvement in swelling compared to those given placebo

- 86 people out of 100 who took NSAIDs reported more than 50% improvement in swelling

- 80 people out of 100 who took placebo reported more than 50% improvement in swelling

Function improvement at 24 hours

20 more people out of 100 who took NSAIDs had improvement in function compared to those given placebo

- 27 people out of 100 who took NSAIDs reported improvement in function

- 7 people out of 100 who took placebo reported improvement in function

Side effects

10 fewer people out of 100 who took NSAIDs reported side effects compared to those given placebo

- 3 people out of 100 who took NSAIDs had side effects

- 13 people out of 100 who took placebo had side effects

There were no withdrawals due to side effects.

Quality of the evidence

Low-certainty evidence from 1 study suggests that NSAIDs may improve pain after 24 hours compared to placebo.

Moderate-certainty evidence shows that NSAIDs probably were equal to COXIBs in reducing pain and inflammation but with more side effects, and NSAIDs probably are equally beneficial as glucocorticoids with regards to pain but are probably less beneficial with regards to swelling, with more side effects. Only low-certainty evidence from single trials was available for the comparisons NSAID versus rilonacept and NSAID versus acupuncture, or one NSAID versus another NSAID, which included NSAIDs no longer in use.

Authors' conclusions: 

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.

Read the full abstract...
Background: 

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.

Objectives: 

To assess the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) (including cyclo-oxygenase-2 (COX-2) inhibitors (COXIBs)) for acute gout.

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

We used standard methodological procedures as expected by Cochrane.

Main results: 

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).

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