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 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).
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.