Source: McKenzie BJ, Wechalekar MD, Johnston RV, Schlesinger N, Buchbinder R. Colchicine for acute gout. Cochrane Musculoskeletal Group, ed. Cochrane Database of Systematic Reviews. 2021;2021(8).
Study Population: 803 patients with acute gout in four trials
Efficacy Endpoints: Global assessment of treatment success (self-reported pain control ≥50%)
Harm Endpoints: Serious adverse events and total adverse events
Narrative: Gout is a common inflammatory condition of the joints. Episodes often begin rapidly and have a duration of days to weeks. The prevalence increases with age, occurring in up to 7% of men over the age of 65 years.1 Gout occurs due to an increase in the serum uric acid, with deposition in the joints eventually leading to inflammation that may present with pain, swelling, and redness (erythema) of the affected joint.2 Gout can be precipitated by toxins (e.g., alcohol), cellular breakdown (e.g., chemotherapy) or joint trauma.2 Although gout is self-resolving, medications can expedite resolution, reduce pain, and help patients return to their normal daily activities. Gout is commonly treated with anti-inflammatory medications, which can include non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, or glucocorticoids. The American College of Rheumatology guidelines recommend that NSAIDs, oral colchicine, or glucocorticoids may all be considered for the treatment of an acute gout flare.3
The systematic review and meta-analysis summarized here identified four trials 4, 5, 6, 7 (n = 803 participants) comparing colchicine with placebo, NSAIDs, or higher doses of colchicine.8 The authors included randomized and quasi-randomized controlled trials of adults (age ≥18 years) with a diagnosis of acute gout. The primary outcome for the review was pain control (defined as the proportion of patients reporting ≥ 50% decrease in pain within the first 32–36h of presentation).8 Total adverse events and serious adverse events were also reported.
Lower-dose colchicine (1.8 mg over 1h) improved pain control compared to placebo (one study, 103 participants, relative risk [RR] = 2.43, 95% confidence interval [CI] = 1.05 to 5.64, absolute risk difference [ARD] = 24.7%, number needed to treat [NNT] = 5, quality of evidence = low) with no difference in adverse events between groups.4 The quality of evidence was downgraded one level due to the risk of selection bias from unclear reporting of the method of randomization and risk of reporting bias. The level of evidence was downgraded a second level for imprecision as the number of events was small (<200) and the 95% CI included a low value with no appreciable benefit.
Higher-dose colchicine (4.8 mg over 6h or 1 mg followed by 0.5 mg every 2h until complete response or adverse events) also improved pain control compared to placebo (two studies, 124 participants, RR = 2.2, 95% CI = 1.3 to 3.7, ARD = 23%, NNT = 4, quality of evidence = low) and increased adverse events (84% in the higher-dose colchicine group vs. 26% in the control group; two studies, 124 participants, RR = 3.2, 95% CI = 2.0 to 5.1, ARD = 58%, number needed to harm [NNH] = 2, quality of evidence = low).4, 5 The quality of evidence was downgraded one level due to the risk of selection bias from unclear reporting of the method of randomization and risk of reporting bias in one study. The level of evidence was downgraded a second level for imprecision because the total number of participants was small and the total number of events was small. Adverse events primarily comprised nausea, vomiting, diarrhea, and abdominal pain. There were no serious adverse events reported in either group.
Compared with lower-dose colchicine (1.8 mg over 1h), higher-dose colchicine (4.8 mg over 6h) did not improve pain control. However, higher-dose colchicine was associated with an increased risk of adverse events (one study, 126 participants, RR = 2.1, 95% CI = 1.5 to 3.0, ARD= 40%, NNH = 3, quality of evidence = low).4 The quality of evidence was downgraded one level due to the risk of selection bias from unclear reporting of the method of randomization and risk of reporting bias. The level of evidence was downgraded a second level for imprecision because the number of events was small (<200) and the 95% CI included a low value with no appreciable benefit. Adverse events primarily comprised nausea, vomiting, diarrhea, and abdominal pain. There were no serious adverse events reported in either group.
Lower-dose colchicine (0.5 mg taken three times per day for 4 days) did not improve pain compared with NSAIDs (naproxen 750 mg at baseline followed by 250 mg every 8h for 7 days) and there was no difference in adverse events (one study, 399 patients).6
Caveats: There are several important limitations to the data reported in this systematic review. First, there were differences in the diagnostic criteria used for gout, with some using joint aspirate while others used the American College of Radiology criteria. There was heterogeneity in doses and timing of the medication among studies. The primary outcome for which the individual studies were powered varied slightly with two mirroring the primary outcome for the review,4, 5 while the other primary outcomes included worst pain in the first 24h6 and recurrence rate within 3 months.7 Additionally, trials used different scales for pain and different time periods for the assessment of outcomes. Only one NSAID (naproxen) was evaluated, so it is unclear if other NSAIDs would be more effective. Moreover, the sample sizes were small, the trials were not powered for adverse events, and comparisons were from only one or two studies, meaning none of these results can be considered broadly reliable. One of the studies did not blind the participants, personnel, or outcome assessors, which may have introduced bias.6 Another study did not report the pain scores despite the methods stating that these data were collected, raising concern for selective reporting bias.4 Further, colchicine and its metabolites are renally and hepatically cleared, but the included studies did not provide data on participant renal or hepatic function. This is important to note because colchicine has a much higher risk of complications (e.g., rhabdomyolysis, seizures, disseminated intravascular coagulation) in the case of overdose or inadequate excretion than NSAIDs. Finally, despite the common use of corticosteroids in gout, there were no RCTs comparing the effectiveness and safety between these two interventions, limiting the translation of this evidence into practice. Similarly, multimodal therapy (e.g., NSAIDs with colchicine vs. colchicine alone) was also not studied.
Colchicine was associated with better pain control and more adverse events than placebo for acute gouty arthritis in small studies. Given the limitations of these studies, we have assigned a color recommendation of yellow (unclear if benefits) to this intervention particularly in light of the lack of benefit over common NSAIDs. Future studies should be performed with larger sample sizes that factor in patient comorbidities.
The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.
Author: Michael Gottlieb, MD; Willeed Rabah, MD; Brit Long, MD
Supervising Editors: Shahriar Zehtabchi, MD
Published/Updated: December 28, 2021
The title bar is color-coded with our overall recommendation.