Gout

Martin Underwood

. 2011 May 17;2011:1120.

Gout

Martin Underwood ¹

PMCID: PMC3275296 PMID: 21575286

Abstract

Introduction

Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute gout? What are the effects of treatments to prevent gout in people with prior acute episodes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review, we present information relating to the effectiveness and safety of the following interventions: colchicine, corticosteroids, corticotropin (ACTH), non-steroidal anti-inflammatory drugs (NSAIDs), sulfinpyrazone, xanthine oxidase inhibitors, advice to lose weight, advice to reduce alcohol intake, and advice to reduce dietary intake of purines.

Key Points

Gout is characterised by deposition of urate crystals, causing acute monoarthritis and crystal deposits (tophi) in the skin.

Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.
Diagnosis is usually clinical, supported by presence of hyperuricaemia.
Risk factors are those associated with hyperuricaemia, including: older age; non-white ethnicity; obesity; consumption of alcohol, meat, and fish; and use of diuretics.
Hyperuricaemia may be associated with an increased risk of cardiovascular events; we don't know whether it is an independent risk factor.

We don't know whether NSAIDs reduce pain and tenderness in an acute attack of gout, although they are commonly used in clinical practice. They are associated with increased risks of gastrointestinal, and possible cardiovascular, adverse effects.

Indometacin is widely used to treat acute gout despite the absence of RCT evidence of benefit. Etoricoxib is as effective as indometacin with reduced risks of gastrointestinal adverse effects.

Colchicine may be more effective than placebo at improving symptoms in acute gout. Its use is limited by the high incidence of adverse effects; although these may be reduced with low-dose colchicine regimens.

Low-dose colchicine may be as effective at reducing pain in gout and may produce fewer adverse effects than high-dose colchicine.

We don't know whether intra-articular or parenteral corticosteroids, or corticotropin (ACTH), improve symptoms in acute gout.

Oral corticosteroids seem as effective as NSAIDs and may have fewer short-term adverse events.

We don't know whether colchicine prevents attacks of gout in people with prior episodes, but it may reduce the risk of an attack in a person starting allopurinol treatment.

We don't know whether advice to lose weight or reduce alcohol or dietary purine intake prevents further attacks of gout.

We don't know whether sulfinpyrazone reduces the risk of recurrent attacks compared with placebo or other treatments.

We don't know whether xanthine oxidase inhibitors reduce the risk of recurrent attacks in the long term when compared with placebo or other treatments. Higher doses of febuxostat may increase the risks of gout attacks within the first 8 weeks of treatment compared with placebo, and compared with allopurinol.

About this condition

Definition

Gout is a syndrome caused by deposition of urate crystals. It typically presents as an acute monoarthritis of rapid onset. The first metatarsophalangeal joint is the most commonly affected joint (podagra). Gout also affects other joints; joints in the foot, ankle, knee, wrist, finger, and elbow are the most frequently affected. Crystal deposits (tophi) may develop around hands, feet, elbows, and ears. Diagnosis: This is usually made clinically. The American College of Rheumatology (ACR) criteria for diagnosing gout are as follows: (1) characteristic urate crystals in joint fluid; (2) a tophus proved to contain urate crystals; or (3) the presence of 6 or more defined clinical laboratory and x-ray phenomena (see table 1 ). We have included studies of people meeting the ACR criteria, studies in which the diagnosis was made clinically, and studies that used other criteria.

Table 1.

American College of Rheumatology criteria for acute gout (people must fulfil at least 6 criteria).


1	More than 1 attack of acute arthritis
2	Maximum inflammation developed within 1 day
3	Monoarthritis attack
4	Redness observed over joints
5	First metatarsophalangeal joint painful or swollen
6	Unilateral first metatarsophalangeal joint attack
7	Unilateral tarsal joint attack
8	Tophus (proved or suspected)
9	Hyperuricaemia
10	Asymmetric swelling within a joint on x-ray film
11	Subcortical cysts without erosions on x-ray film
12	Joint culture negative for organism during attack

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Incidence/ Prevalence

Gout is more common in older people and men. In people aged 65 to 74 years in the UK, the prevalence is about 50/1000 in men and about 9/1000 in women. The annual incidence of gout in people aged over 50 years in the US is 1.6/1000 in men and 0.3/1000 in women. One 12-year longitudinal study of 47,150 male health professionals with no previous history of gout estimated that annual incidence of gout ranged from 1.0/1000 for those aged 40 to 44 years to 1.8/1000 for those aged 55 to 64 years. Gout may become more common because of increasing longevity, obesity, meat and fish consumption, and use of diuretics. Gout may be more common in some non-white ethnic groups. A pooled analysis of two cohort studies of former medical students found the annual incidence of gout to be 3.1/1000 in black men and 1.8/1000 in white men. After correcting for the higher prevalence of hypertension among black men, which is a risk factor for gout, the relative risk of gout in black men compared with white men was 1.30 (95% CI 0.77 to 2.19). A cross-sectional survey of 657 people aged 15 years and older in New Zealand found a higher prevalence of gout in Maoris than in people of a European background (6.4% in Maoris v 2.9% in people with European background; age-adjusted RR 3.2, 95% CI 1.6 to 6.6).

Aetiology/ Risk factors

Urate crystals form when serum urate concentration exceeds 0.42 mmol/L. Serum urate concentration is the principal risk factor for a first attack of gout, although 40% of people have normal serum urate concentration during an attack of gout. A cohort study of 2046 men followed up for about 15 years found that the annual incidence was about 0.4% in men with a urate concentration of 0.42 mmol/L to 0.47 mmol/L, rising to 4.3% when serum urate concentration was 0.45 mmol/L to 0.59 mmol/L. One 5-year longitudinal study of 223 asymptomatic men with hyperuricaemia estimated the 5-year cumulative incidence of gout to be 10.8% for those with baseline serum urate of 0.42 mmol/L to 0.47 mmol/L, 27.7% for baseline urate of 0.48 mmol/L to 0.53 mmol/L, and 61.1% for baseline urate levels of 0.54 mmol/L or more. The study found that a 0.6 mmol/L difference in baseline serum urate increased the odds of an attack of gout by a factor of 1.8 (OR adjusted for other risk factors for gout: 1.84, 95% CI 1.24 to 2.72). One 12-year longitudinal study (47,150 male health professionals with no history of gout) estimated that the relative risks of gout associated with one additional daily serving of various foods (weekly for seafood) were as follows: meat 1.21 (95% CI 1.04 to 1.41), seafood (fish, lobster, and shellfish) 1.07 (95% CI 1.01 to 1.12), purine-rich vegetables 0.97 (95% CI 0.79 to 1.19), low-fat dairy products 0.79 (95% CI 0.71 to 0.87), and high-fat dairy products 0.99 (95% CI 0.89 to 1.10). Alcohol consumption of >14.9 g daily significantly increased the risk of gout compared with no alcohol consumption (RR for 15.0–29.9 g/day 1.49, 95% CI 1.14 to 1.94; RR for 30.0–49.9 g/day 1.96, 95% CI 1.48 to 2.60; RR for at least 50 g/day 2.53, 95% CI 1.73 to 3.70). The longitudinal study also estimated the relative risk of gout associated with an additional serving of beer (355 mL, 12.8 g alcohol), wine (118 mL, 11.0 g alcohol), and spirits (44 mL, 14.0 g alcohol). It found that an extra daily serving of beer or spirits was significantly associated with gout, but an extra daily serving of wine was not (RR for 355 mL/day beer 1.49, 95% CI 1.32 to 1.70; RR for 44 mL/day spirits 1.15, 95% CI 1.04 to 1.28; RR for 118 mL/day wine 1.04, 95% CI 0.88 to 1.22). Other suggested risk factors for gout include obesity, insulin resistance, dyslipidaemia, hypertension, dietary fructose intake, and cardiovascular disorders.

Prognosis

We found few reliable data about prognosis or complications of gout. One study found that 3 of 11 (27%) people with untreated gout of the first metatarsophalangeal joint had spontaneous resolution after 7 days. A case series of 614 people with gout who had not received treatment to reduce urate levels, and who could recall the interval between first and second attacks, reported recurrence rates of 62% after 1 year, 78% after 2 years, and 84% after 3 years. An analysis of two prospective cohort studies of 371 black and 1181 white male former medical students followed up for about 30 years found no significant difference in risk of CHD in men who had developed gout compared with men who had not (RR 0.85, 95% CI 0.40 to 1.81).

Aims of intervention

For treating gout: to reduce the severity and duration of pain and loss of function, with minimal adverse effects of treatment. For preventing recurrence: to reduce the frequency and severity of recurrent attacks, and minimise the adverse effects of interventions.

Outcomes

For treating gout: symptom severity (pain scores, proportion of people with improved symptoms), adverse effects of treatment. For preventing recurrence (over 6 months): number of recurrent episodes a year, severity of recurrent episodes a year, adverse effects of treatment.

Methods

Clinical Evidence search and appraisal September 2010. The following databases were used to identify studies for this systematic review: Medline 1966 to September 2010, Embase 1980 to September 2010, and The Cochrane Database of Systematic Reviews 2010, Issue 3 [searched online 30 September 2010] (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language. RCTs had to be at least single-blinded where possible to blind — we excluded all studies described as "open", "open label", or not blinded, unless blinding was impossible. RCTs had to contain 20 or more individuals of whom 80% or more were followed up. For question 1 on treatment of acute gout, there was no minimum length of follow-up required to include studies. For question 2 on prevention of recurrent gout, the minimum length of follow-up required to include studies was 6 months or longer, except for xanthine oxidase inhibitors plus prophylactic drugs, where the minimum length of follow-up for inclusion was 3 months. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition, we used a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which were added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Gout.

Important outcomes	Recurrence of gout, Symptom severity
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of treatments for acute gout?
2 (227)	Symptom severity	Colchicine versus placebo	4	–1	0	–1	0	Low	Quality point deducted for poor follow-up in 1 RCT. Directness point deducted for narrow inclusion criteria in 1 RCT
2 (210)	Symptom severity	Corticosteroids versus NSAIDs	4	0	–1	0	0	Moderate	Consistency point deducted for different results at different end points
1 (30)	Symptom severity	NSAIDs versus placebo	4	–2	–1	0	0	Very low	Quality points deducted for sparse data and statistical flaws. Consistency point deducted for conflicting results at different end points
6 (548)	Symptom severity	NSAIDs versus each other	4	–1	0	–1	0	Low	Quality point deducted for incomplete reporting. Directness point deducted for differences in regimens between studies and small number of comparisons
What are the effects of treatments to prevent gout in people with prior acute episodes?
1 (not known)	Recurrence of gout	Sulfinpyrazone versus placebo	4	–2	0	–1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for unreported population details
1 (1072)	Recurrence of gout	Xanthine oxidase inhibitors versus placebo	4	–1	–1	0	0	Low	Quality point deducted for incomplete reporting of results. Consistency point deducted for different results at different time points
2 (1832)	Recurrence of gout	Xanthine oxidase inhibitors versus each other	4	0	–1	0	0	Moderate	Consistency point deducted for different results at different time points and different doses
1 (43)	Recurrence of gout	Xanthine oxidase inhibitors alone versus xanthine oxidase inhibitors plus prophylactic drugs	4	–2	0	0	0	Low	Quality points deducted for sparse data and for uncertainty about basis of statistical analysis

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We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Moderate-quality evidence: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Very low-quality evidence: Any estimate of effect is very uncertain.

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

References

1.Emmerson BT. The management of gout. N Engl J Med 1996;334:445–451. [DOI] [PubMed] [Google Scholar]
2.Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895–900. [DOI] [PubMed] [Google Scholar]
3.Kim KY, Schumacher HR, Hunsche E, et al. A literature review of the epidemiology and treatment of acute gout. Clin Ther 2003;25:1593–1616. [DOI] [PubMed] [Google Scholar]
4.Harris CM, Lloyd DC, Lewis J. The prevalence and prophylaxis of gout in England. J Clin Epidemiol 1995;48:1153–1158. [DOI] [PubMed] [Google Scholar]
5.Abbott RD, Brand FN, Kannel WB, et al. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol 1988;41:237–242. [DOI] [PubMed] [Google Scholar]
6.Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004;350:1093–1103. [DOI] [PubMed] [Google Scholar]
7.Bieber JD, Terkeltaub RA. Gout: on the brink of novel therapeutic options for an ancient disease. Arthritis Rheum 2004;50:2400–2414. [DOI] [PubMed] [Google Scholar]
8.Hochberg MC, Thomas J, Thomas DJ, et al. Racial differences in the incidence of gout. The role of hypertension. Arthritis Rheum 1995;38:628–632. [DOI] [PubMed] [Google Scholar]
9.Klemp P, Stansfield SA, Castle B, et al. Gout is on the increase in New Zealand. Ann Rheum Dis 1997;56:22–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
10.McGill NW. Gout and other crystal-associated arthropathies. Baillieres Best Pract Res Clin Rheumatol 2000;14:445–460. [DOI] [PubMed] [Google Scholar]
11.Lin KC, Lin HY, Chou P. The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study. J Rheumatol 2000;27:1501–1505. [PubMed] [Google Scholar]
12.Schlesinger N, Baker DG, Schumacher HR Jr. Serum urate during bouts of acute gouty arthritis. J Rheumatol 1997;24:2265–2266. [PubMed] [Google Scholar]
13.Logan JA, Morrison E, McGill PE. Serum uric acid in acute gout. Ann Rheum Dis 1997;56:696–697. [DOI] [PMC free article] [PubMed] [Google Scholar]
14.Stewart OJ, Silman AJ. Review of UK data on the rheumatic diseases –4. Gout. Br J Rheumatol 1990;29:485–488. [DOI] [PubMed] [Google Scholar]
15.Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med 1987;82:421–426. [DOI] [PubMed] [Google Scholar]
16.Choi HK, Atkinson K, Karlson EW, et al. Alcohol intake and risk of incident gout in men: a prospective study. Lancet 2004;363:1277–1281. [DOI] [PubMed] [Google Scholar]
17.Culleton BF. Uric acid and cardiovascular disease: a renal-cardiac relationship? Curr Opin Nephrol Hypertens 2001;10:371–375. [DOI] [PubMed] [Google Scholar]
18.Bryan E. Are gout and increased uric acid levels risk factors for cardiac disease? In: Center for Clinical Effectiveness Series 2002: Aetiology. Clayton, Australia: Monash Institute of Health Services Research, 2002. [Google Scholar]
19.Choi HK, Curhan G, Choi Hyon K, et al. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ 2008;336:309–312. [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Bellamy N, Downie WW, Buchanan WW. Observations on spontaneous improvement in patients with podagra: implications for therapeutic trials of non-steroidal anti-inflammatory drugs. Br J Clin Pharmacol 1987;24:33–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Yu TF, Gutman AB. Efficacy of colchicine prophylaxis in gout. Ann Intern Med 1961;55:179–192. [DOI] [PubMed] [Google Scholar]
22.Gelber AC, Klag MJ, Mead LA, et al. Gout and risk for subsequent coronary heart disease. The Meharry-Hopkins Study. Arch Intern Med 1997;157:1436–1440. [PubMed] [Google Scholar]
23.Schlesinger N, Schumacher R, Catton M, et al. Colchicine for acute gout. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. 17054279 [Google Scholar]
24.Ahern MJ, Reid C, Gordon TP, et al. Does colchicine work? The results of the first controlled study in acute gout. Aust N Z J Med 1987;17:301–304. [DOI] [PubMed] [Google Scholar]
25.Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum 2010;62:1060–1068. [DOI] [PubMed] [Google Scholar]
26.Schlesinger N, Schumacher HR Jr. Gout: can management be improved? Curr Opin Rheumatol 2001;13:240–244. [DOI] [PubMed] [Google Scholar]
27.Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila.) 2010;48:407–414. [DOI] [PubMed] [Google Scholar]
28.Underwood M. Diagnosis and management of gout. BMJ 2006;332:1315–1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Janssens HJ, Lucassen PL, Van de Laar FA, et al. Systemic corticosteroids for acute gout. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007. 18425920 [Google Scholar]
30.Man CY, Cheung IT, Cameron PA, et al. Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial. Ann Emerg Med 2007;49:670–677. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Janssens HJ, Janssen M, Van de Lisdonk EH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008;371:1854–1860. [DOI] [PubMed] [Google Scholar]
32.Taylor CT, Brookes NC, Kelley KW. Corticotropin for acute management of gout. Ann Pharmacother 2001:35:365–368. [DOI] [PubMed] [Google Scholar]
33.Sutaria, S, Katbamna, R, Underwood M. Effectiveness of interventions for the treatment of acute and prevention of recurrent gout: a systematic review. Rheumatology 2006;45:1422–1431. Search date 2005. [DOI] [PubMed] [Google Scholar]
34.Garcia de la Torre I. Double-blind parallel study comparing tenoxicam and placebo in acute gouty arthritis. Invet Med Int 1987;14:92–97. [In Spanish] [Google Scholar]
35.Rubin BR, Burton R, Navarra S, et al. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial. Arthritis Rheum 2004;50:598–606. [DOI] [PubMed] [Google Scholar]
36.Schumacher HR Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. BMJ 2002;324:1488–1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
37.Maccagno A, Di Giorgio E, Romanowicz A. Effectiveness of etodolac ("Lodine") compared with naproxen in patients with acute gout. Curr Med Res Opin 1991;12:423–429. [DOI] [PubMed] [Google Scholar]
38.Lederman R. A double-blind comparison of etodolac (Lodine) and high doses of naproxen in the treatment of acute gout. Adv Ther 1990;7:344–354. [Google Scholar]
39.Altman RD, Honig S, Levin JM, et al. Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol 1988;15:1422–1426. [PubMed] [Google Scholar]
40.Lomen PL, Turner LF, Lamborn KR, et al. Flurbiprofen in the treatment of acute gout. A comparison with indomethacin. Am J Med 1986;80:134–139. [DOI] [PubMed] [Google Scholar]
41.Fraser RC, Davis RH, Walker FS. Comparative trial of azapropazone and indomethacin plus allopurinol in acute gout and hyperuricaemia. J R Coll Gen Pract 1987;37:409–411. [PMC free article] [PubMed] [Google Scholar]
42.Non-steroidal anti-inflammatory drugs. In: Royal Pharmaceutical Society of Great Britain, eds. British National Formulary. Wallingford: Pharmaceutical Press, 2008:543–552. [Google Scholar]
43.Cheng TT, Lai HM, Chiu CK, et al. A single-blind, randomized, controlled trial to assess the efficacy and tolerability of rofecoxib, diclofenac sodium, and meloxicam in patients with acute gouty arthritis. Clin Ther 2004;26:399–406. [DOI] [PubMed] [Google Scholar]
44.Willburger RE, Mysler E, Derbot J, et al. Lumiracoxib 400 mg once daily is comparable to indomethacin 50 mg three times daily for the treatment of acute flares of gout. Rheumatology 2007;46:1126–1132. [DOI] [PubMed] [Google Scholar]
45.Anon. Gout in primary care. Drug Ther Bull 2004;42:37–40. [DOI] [PubMed] [Google Scholar]
46.National Institute for Health and Clinical Excellence. Osteoarthritis. The care and management of osteoarthritis in adults. NICE Clinical Guideline CG 59. 2008. Available at http://www.nice.org.uk/CG59 (last accessed 18 April 2011). [Google Scholar]
47.Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum 2008;59:1540–1548. [DOI] [PubMed] [Google Scholar]
48.Becker MA, Schumacher, HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005;353:2450–2461. [DOI] [PubMed] [Google Scholar]
49.Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol 2004;31:2429–244. [PubMed] [Google Scholar]
50.Gibson T, Rodgers V, Potter C, et al. Allopurinol treatment and its effect on renal function in gout: a controlled study. Ann Rheum Dis 1982;41:59–65. [DOI] [PMC free article] [PubMed] [Google Scholar]

BMJ Clin Evid. 2011 May 17;2011:1120.

Colchicine (oral) for treating acute gout

Summary

Colchicine may be more effective than placebo at improving symptoms in acute gout. Its use is limited by the high incidence of adverse effects, although these may be much reduced with low-dose colchicine regimens.

Low-dose colchicine may be as effective at reducing pain in gout and may produce fewer adverse effects than high-dose colchicine.

Benefits and harms

Colchicine versus placebo:

We found one systematic review (search date 2006), which found one RCT. We found one subsequent RCT.

Symptom severity

Compared with placebo Colchicine may be more effective than placebo at reducing pain at 48 hours, and may increase the proportion of people with 50% or more reduction in pain at 24 hours, in people with gout (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Pain
RCT	43 hospital inpatients with acute gout confirmed by synovial fluid examination, aged 55 to 91 years, 40/43 (93%) men In review	Pain assessed on a 10-cm visual analogue scale; proportion of people with at least 50% improvement in pain 48 hours 16/22 (73%) with colchicine (1 mg followed by 0.5 mg every 2 hours as tolerated or until complete response) 8/22 (36%) with placebo	RR 2.00 95% CI 1.09 to 3.68 P <0.05	Small effect size	colchicine
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Proportion of people with at least 50% pain reduction without rescue medication 24 hours 17/52 (33%) with high-dose colchicine (4.8 mg orally, given over 6 hours) 9/58 (16%) with placebo	OR 2.64 95% CI 1.06 to 6.62 P = 0.034	Moderate effect size	high-dose colchicine
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Proportion of people with at least 50% pain reduction without rescue medication 24 hours 28/74 (40%) with low-dose colchicine (1.8 mg orally, given over 1 hour) 9/58 (16%) with placebo	OR 3.31 95% CI 1.41 to 7.77 P = 0.005	Moderate effect size	low-dose colchicine

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
RCT	43 hospital inpatients with acute gout confirmed by synovial fluid examination, aged 55 to 91 years, 40/43 (93%) men	Proportion of people with nausea, diarrhoea, or vomiting 22/22 (100%) with colchicine 5/21 (24%) with placebo	Significance assessment not reported
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Adverse effects 40/52 (77%) with high-dose colchicine (4.8 mg orally, given over 6 hours) 16/58 (27%) with placebo	OR 9.0 95% CI 3.8 to 21.2	Large effect size	placebo
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Adverse effects 27/74 (37%) with low-dose colchicine (1.8 mg orally, given over 1 hour) 16/58 (27%) with placebo	OR 1.5 95% CI 0.7 to 3.2		Not significant
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Gastrointestinal adverse effects 40/52 (77%) with high-dose colchicine given over 6 hours (4.8 mg orally) 12/59 (20%) with placebo	OR 13.1 95% CI 5.3 to 32.3	Large effect size	placebo
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Gastrointestinal adverse effects 19/74 (26%) with low-dose colchicine given over 1 hour (1.8 mg orally) 12/59 (20%) with placebo	OR 1.4 95% CI 0.6 to 3.1		Not significant
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Severe intensity adverse effects 10/52 (19%) with high-dose colchicine (4.8 mg orally, given over 6 hours) 1/59 (2%) with placebo	OR 13.8 95% CI 1.7 to 112	Large effect size	placebo
RCT 3-armed trial	575 people who were able to start treatment within 12 hours of a gout attack randomised between attacks; 184 people who subsequently developed acute gout included in analysis (see further information on studies)	Severe intensity adverse effects 0/74 (0%) with low-dose colchicine (1.8 mg, given over 1 hour) 1/59 (2%) with placebo	Significance assessment not reported

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Colchicine versus NSAIDs:

We found one systematic review (search date 2006), which found no RCTs. We found no subsequent RCTs.

Colchicine versus corticosteroids:

We found one systematic review (search date 2006), which found no RCTs. We found no subsequent RCTs.

Further information on studies

The RCT found that 5/21 (24%) people taking placebo developed nausea (significance assessment not performed). The 50% improvement in pain occurred before diarrhoea and vomiting in 9/22 (40%) people, after the onset of diarrhoea and vomiting in 12/22 (55%) people, and at the same time in 1/22 (5%) people.

This RCT included both male and postmenopausal female patients, aged at least 18 years, with at least two attacks of gout in the previous year, who met ACR classification criteria. The RCT randomised 575 people (95% male, mean age 51 years) to take either low-dose colchicine, high-dose colchicine, or placebo if they had an acute gout flare during the study timeframe. A total of 185/575 (32%) randomised people experienced a confirmed gout flare and took the medication, and were included in the analysis.

The RCT found that high-dose colchicine significantly increased incidence of overall adverse effects and gastrointestinal adverse effects compared with low-dose colchicine (overall adverse effects: OR 5.8, 95% CI 2.6 to 12.9; gastrointestinal adverse effects: OR 9.6, 95% CI 4.2 to 22.1).

Comment

Clinical guide:

Colchicine has been used since antiquity to treat gout. A large number of observational studies support its use. Although it is likely to be beneficial, it has a narrow benefit-to-toxicity ratio that limits use of higher doses in people with gout. Lower dose colchicine regimens that typically use 1.5 mg to 2.0 mg over 24 hours may have fewer adverse effects than higher doses and still be effective.

Substantive changes

Colchicine (oral) for treating acute gout New evidence added. Categorisation changed from Unknown effectiveness to Likely to be beneficial.

BMJ Clin Evid. 2011 May 17;2011:1120.

Corticosteroids

Summary

We don't know whether intra-articular, parenteral, or oral corticosteroids improve symptoms in acute gout.

Oral corticosteroids seem as effective as NSAIDs and may have fewer short-term adverse events.

Benefits and harms

Corticosteroids versus placebo:

We found one systematic review (search date 2007), which identified no RCTs. We found no subsequent RCTs.

Corticosteroids versus NSAIDs:

We found one systematic review (search date 2007), which found one RCT. We found one subsequent RCT.

Symptom severity

Compared with NSAIDs Corticosteroids and NSAIDs seem to be equally effective at reducing pain in people with acute arthritis suggestive of gout (moderate-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Pain
RCT	90 people with an acute arthritis suggestive of gout, 74 men, mean age 65 years In review	Mean rate of decrease in pain score (assessed on a 100-mm visual analogue scale) 2 hours 6.4 mm/hour with indometacin 9.5 mm/hour with prednisolone	Mean difference +3.2 mm/hour 95% CI –0.78 mm/hour to +7.14 mm/hour P = 0.12 Equivalence satisfied (see further information on studies)		Not significant
RCT	90 people with an acute arthritis suggestive of gout, 74 men, mean age 65 years In review	Mean rate of decrease in pain score (assessed on a 100-mm visual analogue scale) days 1 to 14 0.3 mm/day with indometacin 0.7 mm/day with prednisolone	Mean difference 0.5 mm/day 95% CI 0.03 mm/day to 0.89 mm/day P = 0.04	Effect size not calculated	prednisolone
RCT	90 people with an acute arthritis suggestive of gout, 74 men, mean age 65 years In review	Mean rate of decrease in pain score (assessed on a 100-mm visual analogue scale) 2 weeks with indometacin with prednisolone Absolute results not reported	Reported as not significant P value not reported		Not significant
RCT	120 people with acute gout confirmed by identification of monosodium urate crystals in synovial fluid from the affected joint; mean age 57 years, 89% men	Pain reduction (assessed on a 100-mm visual analogue scale, higher values indicating greater pain) 90 hours 44.7 mm with prednisolone (35 mg once daily) 46.0 mm with naproxen (500 mg twice daily)	Difference between groups +1.3 mm 95% CI –9.8 to +7.1 Equivalence satisfied (see further information on studies)		Not significant
RCT	120 people with acute gout confirmed by identification of monosodium urate crystals in synovial fluid from the affected joint; mean age 57 years, 89% men	Mean pain reduction (assessed by 100-mm visual analogue scale, higher numbers indicating greater pain) at each of 8 follow-up time points up to 90 hours –5.6 mm with prednisolone (35 mg once daily) –5.8 mm with naproxen (500 mg twice daily)	Difference between groups +1.57 mm 95% CI –8.65 to +11.78 Equivalence not satisfied (see further information on studies)		Not significant

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
RCT	90 people with an acute arthritis suggestive of gout, 74 men, mean age 65 years In review	Total adverse effects 29/46 (63%) with indometacin 12/44 (27%) with prednisolone	P = 0.0007	Effect size not calculated	prednisolone
RCT	90 people with an acute arthritis suggestive of gout, 74 men, mean age 65 years In review	Epigastric pain 14/30 (30%) with indometacin 0/44 (0%) with prednisolone	P <0.0001	Effect size not calculated	prednisolone
RCT	90 people with an acute arthritis suggestive of gout, 74 men, mean age 65 years In review	Gastrointestinal haemorrhage 5/46 (11%) with indometacin 0/44 (0%) with prednisolone	P <0.05	Effect size not calculated	prednisolone
RCT	90 people with an acute arthritis suggestive of gout, 74 men, mean age 65 years In review	Hospital admission rates because of serious adverse effects 7/46 (15%) with indometacin 0/44 (0%) with prednisolone	P <0.007	Effect size not calculated	prednisolone
RCT	120 people with acute gout confirmed by identification of monosodium urate crystals in synovial fluid from the affected joint; mean age 57 years, 89% men	Adverse effects 34% with prednisolone (35 mg once daily) 37% with naproxen (500 mg twice daily) Absolute numbers not reported	P = 0.42		Not significant
RCT	120 people with acute gout confirmed by identification of monosodium urate crystals in synovial fluid from the affected joint; mean age 57 years, 89% men	Gastric or abdominal pain 15% with prednisolone (35 mg once daily) 15% with naproxen (500 mg twice daily) Absolute numbers not reported			Not significant

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Corticosteroids versus colchicine:

We found one systematic review (search date 2007), which found no RCTs. We found no subsequent RCTs.

Colchicine versus corticotropin:

See benefits and harms of corticotropin.

Further information on studies

The RCT comparing prednisolone versus naproxen was designed as an equivalence trial to show whether the two treatments were equivalent, rather than whether one was superior to the other. Whether the "not significant" result means that the two treatments are equivalent in effectiveness depends on the 95% confidence interval of the effect falling within the pre-defined margin of equivalence (in this RCT arbitrarily chosen as 10%). For the outcome of pain reduction at 90 hours, the RCT found that the treatments were equivalent; however, for the outcome of mean pain reduction at 8 follow-up times up to 90 hours, although the difference between groups was not significant, the result was inconclusive with respect to whether the treatments were equivalent.

This RCT has some of the features of an equivalence study with a pre-defined limit for equivalence (± 13 mm visual analogue scale). This criterion for equivalence was satisfied for this outcome.

Comment

Clinical guide:

Both high-dose oral NSAIDs and high-dose colchicine have a high incidence of adverse events. Adverse events from occasional short courses of oral corticosteroids are uncommon. Two RCTs comparing NSAIDs and prednisolone found them to have similar effectiveness. In one of these RCTs, significantly more people in the NSAID groups developed serious adverse effects. Oral corticosteroids may be preferable to either NSAIDs or high-dose colchicine for the occasional treatment of acute gout.

Potential harms of oral corticosteroids are covered elsewhere in Clinical Evidence (see reviews on rheumatoid arthritis and asthma).

Substantive changes

Corticosteroids New evidence added. Categorisation unchanged (Unknown effectiveness), as there remains insufficient evidence to judge the effects of this intervention.

BMJ Clin Evid. 2011 May 17;2011:1120.

Corticotropin (adrenocorticotrophic hormone)

Summary

We don't know whether intra-articular, parenteral, or oral corticotropin (ACTH) improves symptoms in acute gout.

We found no clinically important results from RCTs about the effects of corticotropin compared with no active treatment or NSAIDs.

Benefits and harms

Corticotropin (adrenocorticotrophic hormone [ACTH]) versus placebo:

We found one systematic review (search date 2007), which found no RCTs. We found no subsequent RCTs.

Corticotropin versus NSAIDs:

We found one systematic review (search date 2007), which found no RCTs. We found no subsequent RCTs.

Corticotropin versus corticosteroids:

We found one systematic review (search date 2007), which found no RCTs satisfying Clinical Evidence inclusion criteria.

Further information on studies

None.

Comment

Clinical guide:

Some observational data suggest that corticotropin may be worth considering for people who cannot tolerate other treatments.

Substantive changes

Corticotropin (adrenocorticotrophic hormone) No new evidence added. Existing evidence reevaluated and one previously reported RCT excluded due to lack of blinding. Categorisation unchanged (Unknown effectiveness).

BMJ Clin Evid. 2011 May 17;2011:1120.

NSAIDs

Summary

Indometacin is widely used to treat acute gout despite the absence of RCT evidence of benefit. Etoricoxib is as effective as indometacin with reduced risks of gastrointestinal adverse effects.

NSAIDs seem as effective as oral corticosteroids, but may be associated with more short-term adverse effects.

We found no direct information from RCTs about whether other NSAIDs are better than no active treatment or oral colchicine in people with gout.

Benefits and harms

NSAIDs versus placebo:

We found one systematic review (search date 2005),which found one RCT.

Symptom severity

Compared with placebo NSAIDs (tenoxicam) may be more effective at reducing pain at 1 day, but may be no more effective at reducing pain at 4 days, in people with acute gout (very low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Pain
RCT	30 people, aged 21 to 70 years, with gout of the knee, ankle, wrist, big toe, or elbow In review	Proportion of people showing at least a 50% reduction in pain (pain assessed on a 4-point scale: "disappeared", "improved by at least 50%", "unchanged or improved by <50%", or "increased") 1 day 10/15 (67%) with tenoxicam 4/15 (26%) with placebo	P <0.05	Effect size not calculated	tenoxicam
Tenderness
RCT	30 people, aged 21 to 70 years, with gout of the knee, ankle, wrist, big toe, or elbow In review	Proportion of people showing at least a 50% reduction in tenderness (assessed on a 4-point scale: "disappeared", "improved by at least 50%", "unchanged or improved by <50%", or "increased") 1 day 6/15 (40%) with tenoxicam 1/15 (7%) with placebo	P <0.05	Effect size not calculated	tenoxicam
Pain on mobilisation
RCT	30 people, aged 21 to 70 years, with gout of the knee, ankle, wrist, big toe, or elbow In review	Proportion of people showing at least a 50% reduction in pain on mobilisation (assessed on a 4-point scale: "disappeared", "improved by at least 50%", "unchanged or improved by <50%", or "increased") 1 day 4/15 (27%) with tenoxicam 1/15 (7%) with placebo	P <0.05	Effect size not calculated	tenoxicam
Physician-rated efficacy
RCT	30 people, aged 21 to 70 years, with gout of the knee, ankle, wrist, big toe, or elbow In review	Proportion of people with improvement rated as "good or excellent" 4 days 7/15 (47%) with tenoxicam 4/15 (27%) with placebo	Reported as not significant P value not reported		Not significant

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Adverse effects

No data from the following reference on this outcome.

NSAIDs versus each other:

We found one systematic review (search date 2005), which identified 9 RCTs comparing different NSAIDs versus each other. Two of the high-quality RCTs identified in the review were designed as equivalence studies comparing indometacin 50 mg three times daily versus etoricoxib 120 mg daily. Four of the remaining 7 RCTs identified in the systematic review satisfied our inclusion criteria.

Symptom severity

Compared with each other Indometacin and etoricoxib may be equally effective at reducing pain in people with acute gout. We don't know how any other two NSAIDs compare with each other at reducing pain in people with acute gout (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Pain
RCT	189 people, gout for <48 hours, who had previously responded to NSAIDs, 93% male, mean age 52 years In review	Pain rating (measured on Likert scale: 0 = no pain to 4 = extreme pain) days 2 to 5 with indometacin (50 mg 3 times daily) with etoricoxib (120 mg/day) Absolute results not reported	Difference: –0.08 95% CI –0.29 to +0.13 Equivalence satisfied (see further information on studies)		Not significant
RCT	150 men, gout for <24 hours, mean age 49 years In review Data from 1 RCT	Pain rating (measured on Likert scale: 0 = no pain to 4 = extreme pain) days 2 to 5 with indometacin (50 mg 3 times daily) with etoricoxib (120 mg/day) Absolute results not reported	Difference: +0.11 95% CI –0.14 to +0.35 Equivalence satisfied (see further information on studies)		Not significant
RCT	61 people, aged 18 to 75 years In review	Mean pain scores assessed on a scale 0 to 5 (higher scores indicating worse pain) day 2 2.6 with etodolac (300 mg twice daily) 2.8 with naproxen (500 mg twice daily)	Reported as not significant P value not reported		Not significant
RCT	61 people, aged 18 to 75 years In review	Mean pain scores assessed on a scale 0 to 5 (higher scores indicating worse pain) day 4 1.8 with etodolac (300 mg twice daily) 2.0 with naproxen (500 mg twice daily)	Reported as not significant P value not reported		Not significant
RCT	61 people, aged 18 to 75 years In review	Mean pain scores assessed on a scale 0 to 5 (higher scores indicating worse pain) day 7 1.4 with etodolac (300 mg twice daily) 1.4 with naproxen (500 mg twice daily)	Reported as not significant P value not reported		Not significant
RCT	60 people, aged 18 to 75 years In review	Pain (as assessed on a 5-point rating scale: 1 = no pain to 5 = very severe pain) days 1 to 7 with etodolac (300 mg twice daily) with naproxen (500 mg twice daily) Absolute results reported graphically	Reported as not significant P value not reported		Not significant
RCT	59 people, gout for <48 hours, aged 35 to 88 years In review	Mean pain scores (as assessed on a 4-point scale: 0 = no pain to 3 = severe pain) day 2 0.9 with indometacin (up to 225 mg for 1 day in divided doses followed by 50 mg 3 times daily) 1.1 with ketoprofen (450 mg in divided doses for 1 day followed by 100 mg 3 times daily)	Reported as not significant P value not reported		Not significant
RCT	59 people, gout for <48 hours, aged 35 to 88 years In review	Mean pain scores (as assessed on a 4-point scale: 0 = no pain to 3 = severe pain) day 5 0.8 with indometacin (up to 225 mg for 1 day in divided doses followed by 50 mg 3 times daily) 1.3 with ketoprofen (450 mg in divided doses for 1 day followed by 100 mg 3 times daily)	Reported as not significant P value not reported		Not significant
RCT	59 people, gout for <48 hours, aged 35 to 88 years In review	Mean pain scores (as assessed on a 4-point scale: 0 = no pain to 3 = severe pain) day 8 0.3 with indometacin (up to 225 mg for 1 day in divided doses followed by 50 mg 3 times daily) 0.4 with ketoprofen (450 mg in divided doses for 1 day followed by 100 mg 3 times daily)	Reported as not significant P value not reported		Not significant
RCT	29 people In review	Proportion of people with improved pain 2 days 11/12 (92%) with indometacin (50 mg 4 times daily for 4 days followed by 25 mg 4 times daily for 5 days) 11/12 (92%) with flurbiprofen (100 mg 4 times daily for 1 day followed by 50 mg 4 times daily for 5 days)	Reported as not significant P value not reported		Not significant

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
RCT	189 people, gout for <48 hours, who had previously responded to NSAIDs, 93% male, mean age 52 years In review	Proportion of people reporting at least 1 adverse event 49/86 (57%) with indometacin (50 mg 3 times daily) 45/103 (44%) with etoricoxib (120 mg/day) Absolute results not reported	P = 0.08		Not significant
RCT	189 people, gout for <48 hours, who had previously responded to NSAIDs, 93% male, mean age 52 years In review	Drug-related adverse events 32/86 (37%) with indometacin (50 mg 3 times daily) 17/103 (17%) with etoricoxib (120 mg/day)	P = 0.002	Effect size not calculated	etoricoxib
RCT	150 men, gout for <24 hours, mean age 49 years In review	Proportion of people with adverse events 35/75 (47%) with indometacin (50 mg 3 times daily) 17/75 (23%) with etoricoxib (120 mg/day)	P = 0.003	Effect size not calculated	etoricoxib

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No data from the following reference on this outcome.

NSAIDs versus corticosteroids:

See option on corticosteroids.

Further information on studies

The RCT comparing tenoxicam versus placebo conducted multiple significance tests, and no adjustment was reported for this.

No differences in important adverse effect rates were found.

The RCTs comparing etoricoxib versus indometacin were designed as equivalence trials to show whether the two treatments were equivalent, rather than whether one was superior to the other. Whether the "not significant" result means that the two treatments were equivalent in effectiveness depends on the 95% confidence interval of the effect falling within the pre-defined margin of equivalence (in both these RCTs, defined as within ±0.5 units). For the outcome of pain at days 2 to 5, both RCTs found that etoricoxib and indometacin were equivalent.

Comment

NSAIDs versus each other:

Phenylbutazone and indometacin were established as treatments for gout based on uncontrolled studies. Only the comparisons between etoricoxib and indometacin were powered to show equivalence in efficacy between the two compounds tested. We found 6 RCTs comparing phenylbutazone versus other NSAIDs. These were not considered further because phenylbutazone for gout has been restricted in many countries as it can cause aplastic anaemia and other serious adverse effects.

We found one RCT (93 people) comparing indometacin and azapropazone. We have not considered this further as use of azapropazone has been restricted because of a high incidence of gastrointestinal, renal, and hepatic adverse events.

We found one RCT (62 people) comparing meloxicam versus diclofenac versus rofecoxib. We have not considered this study further as rofecoxib has been withdrawn worldwide because of cardiovascular adverse effects. The RCT was not designed to compare meloxicam versus diclofenac directly.

We found one RCT (235 people) comparing lumaricoxib with indometacin. This non-inferiority study found lumaricoxib to be as effective as indometacin at relieving pain. We have not considered this study further as lumaricoxib has since been withdrawn worldwide because of hepatic adverse effects.

Clinical guide:

Although there is little RCT evidence to support their use, traditional NSAIDs, specifically indometacin, are commonly used to treat gout. The choice of NSAID probably depends on doctor or patient preference. Adverse effects of NSAIDs, including COX-2 inhibitors, often do not manifest early in treatment. However, it is usual to prescribe proton pump inhibitors to reduce the incidence of gastrointestinal bleeding because high doses of NSAIDs are used.

The harms of NSAIDs/COX-2 inhibitors are considered in detail elsewhere in Clinical Evidence and include gastrointestinal ulceration and haemorrhage, and increased cardiovascular risk (see review on NSAIDs).

Substantive changes

NSAIDs New evidence added. Categorisation unchanged (Unknown effectiveness), as there remains insufficient evidence to judge the effects of this intervention.

BMJ Clin Evid. 2011 May 17;2011:1120.

Advice to lose weight

Summary

We don't know whether advice to lose weight prevents further attacks of gout.

Benefits and harms

Advice to lose weight:

We found one systematic review (search date 2005), which identified no RCTs. We found no subsequent RCTs.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2011 May 17;2011:1120.

Advice to reduce alcohol intake

Summary

We don't know whether advice to reduce alcohol prevents further attacks of gout.

Benefits and harms

Advice to reduce alcohol intake:

We found one systematic review (search date 2005), which found no RCTs. We found no subsequent RCTs.

Comment

One large 12-year longitudinal study (47,150 male health professionals with no history of gout) found that increased intake of beer or spirits was associated with a significantly increased incidence of gout. However, it found no significant increase in incidence of gout with increased intake of wine (see aetiology).

Substantive changes

No new evidence

BMJ Clin Evid. 2011 May 17;2011:1120.

Advice to reduce dietary intake of purines

Summary

We don't know whether advice to reduce dietary purine intake prevents further attacks of gout.

Benefits and harms

Advice to reduce dietary intake of purines:

We found one systematic review (search date 2005), which found no RCTs assessing advice to reduce dietary purine intake. We found no subsequent RCTs.

Comment

One large longitudinal study (47,150 male health professionals with no history of gout) found that increased intake of meat or seafood was associated with a significantly increased incidence of gout. However, increased intake of purine-rich vegetables did not significantly affect the incidence of gout. It also found that an increased intake of low-fat dairy produce was associated with a significantly reduced incidence of gout (see aetiology).

Substantive changes

No new evidence

BMJ Clin Evid. 2011 May 17;2011:1120.

Colchicine for preventing recurrence

Summary

We don't know whether colchicine prevents attacks of gout in people with prior episodes, but it may reduce the risk of an attack in a person starting allopurinol treatment.

Benefits and harms

Colchicine versus placebo:

We found one systematic review (search date 2005), which found no RCTs. We found no subsequent RCTs.

Colchicine versus advice to lose weight:

See advice to lose weight.

Colchicine versus advice to reduce alcohol:

See advice to reduce alcohol intake.

Colchicine versus advice to reduce dietary intake of purines:

See advice to reduce dietary intake of purines.

Colchicine versus xanthine oxidase inhibitors:

We found one systematic review (search date 2005), which found no RCTs. We found no subsequent RCTs.

Colchicine versus sulfinpyrazone:

We found one systematic review (search date 2005), which found no RCTs. We found no subsequent RCTs.

Colchicine plus xanthine oxidase inhibitors versus xanthine oxidase inhibitors alone:

See xanthine oxidase inhibitors.

Comment

Colchicine plus xanthine oxidase inhibitors versus xanthine oxidase inhibitors alone:

See comment on xanthine oxidase inhibitors.

Clinical guide:

Colchicine, which has been used since antiquity, may be worth considering for the prevention of gout for people who cannot tolerate allopurinol. Colchicine may be associated with adverse effects, particularly at the higher doses used for treatment of acute gout rather than the lower doses used for prevention of gout. See also comment colchicine for treating gout.

Substantive changes

No new evidence

BMJ Clin Evid. 2011 May 17;2011:1120.

Sulfinpyrazone

Summary

We don't know whether sulfinpyrazone reduces the risk of recurrent attacks compared with placebo or other treatments.

Benefits and harms

Sulfinpyrazone versus placebo:

We found one systematic review (search date 2005), which found one RCT, reported as a conference abstract only.

Recurrence of gout

Compared with placebo We don't know whether sulfinpyrazone is more effective at preventing recurrence of gout in people taking colchicine (very low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Recurrence of gout
Systematic review	Population details not reported by review Data from 1 RCT	Number of gout attacks 170 to 173 months 32 with colchicine plus sulfinpyrazone 29 with colchicine plus placebo	Statistical assessment not performed

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Adverse effects

No data from the following reference on this outcome.

Further information on studies

The RCT identified by the review was reported as a conference abstract only.

Comment

None.

Substantive changes

No new evidence

BMJ Clin Evid. 2011 May 17;2011:1120.

Xanthine oxidase inhibitors

Summary

We don't know whether xanthine oxidase inhibitors reduce the risk of recurrent attacks in the long term when compared with placebo or other treatments.

Higher doses of febuxostat may increase the risks of gout attacks within the first 8 weeks of treatment compared with placebo, and compared with allopurinol.

We found no clinically important results from RCTs about the effects of xanthine oxidase inhibitors compared with sulfinpyrazone, colchicine, or lifestyle interventions.

Benefits and harms

Xanthine oxidase inhibitors versus placebo:

We found one systematic review (search date 2005), which found no RCTs. We found one subsequent RCT comparing placebo, allopurinol, and febuxostat (see further information on studies).

Recurrence of gout

Compared with placebo Febuxostat may increase incidence of recurrent gout compared with placebo in the first 8 weeks of treatment, but we don't know whether it is more or less effective in the longer term. We do not know whether allopurinol is more effective than placebo at reducing the recurrence of gout (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Recurrence of gout
RCT 5-armed trial	1072 people with gout, defined using American College of Rheumatology (ACR) criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout 8 weeks 73/262 (28%) with febuxostat 80 mg 27/134 (20%) with placebo	Statistical analysis not reported
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout 8 weeks 97/269 (36%) with febuxostat 120 mg 27/134 (20%) with placebo	P equal to or less than 0.05 for comparisons of febuxostat 120 mg v placebo	Effect size not calculated	placebo
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout 8 weeks 69/134 (46%) with febuxostat 240 mg 27/134 (20%) with placebo	P equal to or less than 0.05 for comparison of febuxostat 240 mg v placebo	Effect size not calculated	placebo
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout 8 weeks 61/268 (23%) with allopurinol 300 mg 27/134 (20%) with placebo	Statistical analysis not reported
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout weeks 8 to 28 with febuxostat 80 mg with placebo Absolute results not reported	Reported as no significant differences between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout weeks 8 to 28 with febuxostat 120 mg with placebo Absolute results not reported	Reported as no significant differences between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout weeks 8 to 28 with febuxostat 240 mg with placebo Absolute results not reported	Reported as no significant differences between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater) aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout weeks 8 to 28 with allopurinol 300 mg with placebo Absolute results not reported	Reported as no significant differences between groups		Not significant

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with any adverse effect 181/267 (68%) with febuxostat 80 mg 97/134 (72%) with placebo	Reported as no significant difference between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with any adverse effect 183/269 (68%) with febuxostat 120 mg 97/134 (72%) with placebo	Reported as no significant difference between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with any adverse effect 98/134 (73%) with febuxostat 240 mg 97/134 (72%) with placebo	Reported as no significant difference between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with any adverse effect 200/268 (75%) with allopurinol 300 mg 97/134 (72%) with placebo	Reported as no significant difference between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with serious adverse effects 11/267 (4%) with febuxostat 80 mg 2/134 (1%) with placebo	Reported as no significant difference between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with serious adverse effects 9/629 (3%) with febuxostat 120 mg 2/134 (1%) with placebo	Reported as no significant difference between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with serious adverse effects 5/134 (4%) with febuxostat 240 mg 2/134 (1%) with placebo	Reported as no significant difference between groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with serious adverse effects 7/268 (3%) with allopurinol 300 mg 2/134 (1%) with placebo	Reported as no significant difference between groups		Not significant

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Xanthine oxidase inhibitors versus sulfinpyrazone:

We found one systematic review (search date 2005), which found no RCTs. We found no subsequent RCTs.

Xanthine oxidase inhibitors versus colchicine:

We found one systematic review (search date 2005), which found no RCTs. We found no subsequent RCTs.

Xanthine oxidase inhibitors versus lifestyle interventions:

We found one systematic review (search date 2005), which found no RCTs. We found no subsequent RCTs.

Xanthine oxidase inhibitors versus each other:

We found one systematic review (search date 2005), which found no RCTs. We found one subsequent RCT comparing three interventions: allopurinol 300 mg daily, febuxostat 80 mg daily, or febuxostat 120 mg daily. All participants also received naproxen 250 mg twice daily or colchicine 0.6 mg daily during the first 8 weeks of treatment, to reduce the increased incidence of gout flares that can occur when urate-lowering medication is initiated. We found one other subsequent RCT comparing placebo, allopurinol, and febuxostat (see further information on studies).

Recurrence of gout

Compared with each other Febuxostat seems to increase incidence of recurrent gout compared with allopurinol in the first 8 weeks of treatment. Allopurinol and febuxostat seem to be similarly effective at preventing recurrence of gout at 9 to 52 weeks (moderate-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Recurrence of gout
RCT 3-armed trial	760 people with a history of gout, mean age 52 years, 96% male	Proportion of people with at least 1 recurrent attack of gout up to 8 weeks 52/251 (21%) with allopurinol 55/255 (22%) with febuxostat 80 mg	Statistical analysis not reported
RCT 3-armed trial	760 people with a history of gout, mean age 52 years, 96% male	Proportion of people with at least 1 recurrent attack of gout up to 8 weeks 52/251 (21%) with allopurinol 90/250 (36%) with feboxostat 120 mg	P <0.001	Effect size not calculated	allopurinol
RCT 3-armed trial	760 people with a history of gout, mean age 52 years, 96% male	Proportion of people with at least one recurrent attack of gout 9 to 52 weeks 150/234 (64%) with allopurinol 147/228 (64%) with febuxostat 80 mg	P = 0.99 for febuxostat 80 mg v allopurinol		Not significant
RCT 3-armed trial	60 people with a history of gout, mean age 52 years, 96% male	Proportion of people with at least one recurrent attack of gout 9 to 52 weeks 150/234 (64%) with allopurinol 150/215 (70%) with febuxostat 120 mg	P = 0.23 for febuxostat 120 mg v allopurinol		Not significant
RCT 5-armed trial	1072 people with gout, defined using American College of Rheumatology (ACR) criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout 8 weeks 61/268 (23%) with allopurinol 73/262 (28%) with febuxostat 80 mg	Statistical analysis not reported for this between groups comparison
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout 8 weeks 61/268 (23%) with allopurinol 97/269 (36%) with febuxostat 120 mg	P equal to or less than 0.05	Effect size not calculated	allopurinol
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people requiring treatment for acute gout 8 weeks 61/268 (23%) with allopurinol 69/134 (46%) with febuxostat 240 mg	P equal to or less than 0.05	Effect size not calculated	allopurinol

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
RCT 3-armed trial	760 people with a history of gout, mean age 52 years, 96% male	Proportion of people with adverse effects 215/253 (85%) with allopurinol 205/256 (80%) with febuxostat 80 mg 189/251 (75%) with febuxostat 120 mg	P = 0.01 for allopurinol v febuxostat 120 mg; other statistical assessments not reported	Effect size not calculated	febuxostat
RCT 3-armed trial	760 people with a history of gout, mean age 52 years, 96% male	Proportion of people with adverse effects considered by the investigators to be possibly, probably, or definitely associated with the study drug 57/253 (23%) with allopurinol 63/256 (25%) with febuxostat 80 mg 60/251 (24%) with febuxostat 120 mg	Differences reported as not significant P value not reported		Not significant
RCT 3-armed trial	760 people with a history of gout, mean age 52 years, 96% male	Serious adverse effects 19/253 (8%) with allopurinol 11/256 (4%) with febuxostat 80 mg 21/251 (8%) with febuxostat 120 mg	Differences reported as not significant P value not reported		Not significant
RCT 3-armed trial	760 people with a history of gout, mean age 52 years, 96% male	Deaths 0/253 (0%) with allopurinol 2/256 (0.8%) with febuxostat 80 mg 2/251 (0.8%) with febuxostat 120 mg	P = 0.31		Not significant
RCT 5-armed trial	1072 people with gout , defined using American College of Rheumatology (ACR) criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with adverse effects 200/268 (75%) with allopurinol 181/267 (68%) with febuxostat 80 mg 183/269 (68%) with febuxostat 120 mg 98/134 (73%) with febuxostat 240 mg	Reported no significant differences between any groups		Not significant
RCT 5-armed trial	1072 people with gout, defined using ACR criteria with serum urate 8.0 mg/dL or greater (0.48 mmol/L or greater), aged 18 to 85 years (mean age 52 years), 94% men	Proportion of people with serious adverse effects 7/268 (3%) with allopurinol 11/267 (4%) with febuxostat 80 mg 5/269 (2%) with febuxostat 120 mg 7/134 (3%) with febuxostat 240 mg	Reported no significant differences between any groups		Not significant

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Xanthine oxidase inhibitors alone versus xanthine oxidase inhibitors plus prophylactic drugs:

We found no systematic review. We found one RCT comparing colchicine 0.6 mg twice daily versus placebo in people starting allopurinol as prevention for recurrent gout. Treatment was continued for 3 months after serum urate reached normal levels. The dose was reduced to once daily in people with renal insufficiency or gastrointestinal adverse effects.

Recurrence of gout

Xanthine oxidase inhibitors alone compared with xanthine oxidase inhibitors plus prophylactic drugs Initiating treatment with allopurinol alone may be less effective than initiating treatment with allopurinol during colchicine prophylaxis at reducing the risk of recurrent attacks of gout at 6 months (low-quality evidence).

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Recurrence of gout
RCT	43 people starting treatment with allopurinol for chronic gouty arthritis	Proportion of people with at least 1 attack 6 months 7/21 (33%) with allopurinol plus colchicine (12 attacks in total) 17/22 (77%) with allopurinol plus placebo (65 attacks in total)	P = 0.008 The authors report that the finding was significant, but the basis of the statistical analysis was not clear	Effect size not calculated	allopurinol plus colchicine
RCT	43 people starting treatment with allopurinol for chronic gouty arthritis	Severity of attacks (median score on visual analogue scale [scale range not reported]) 6 months 3.64 with allopurinol plus colchicine 5.08 with allopurinol plus placebo	P = 0.018	Effect size not calculated	allopurinol plus colchicine
RCT	43 people starting treatment with allopurinol for chronic gouty arthritis	Mean duration of attacks 6 months 6.00 days with allopurinol plus colchicine 5.56 days with allopurinol plus placebo	P = 0.566		Not significant

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Adverse effects

Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
RCT	43 people starting treatment with allopurinol for chronic gouty arthritis	Diarrhoea 38% with allopurinol plus colchicine 5% with allopurinol plus placebo Absolute numbers not reported	P = 0.009	Effect size not calculated	allopurinol plus placebo

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Further information on studies

The RCT reported that no one withdrew because of diarrhoea, and all cases resolved when the dose was reduced.

This RCT compared 5 interventions: placebo; allopurinol 300 mg daily, depending on renal function (10/268 received 100 mg/day because of impaired renal function); febuxostat 80 mg daily; febuxostat 120 mg daily; or febuxostat 240 mg daily. Participants who had not previously had urate-lowering therapy also received naproxen 250 mg twice daily or colchicine 0.6 mg daily during the first 8 weeks of treatment to reduce the increased incidence of gout flares that can occur when urate-lowering medication is initiated.

Comment

We found one open RCT comparing colchicine 0.5 mg twice daily versus colchicine 0.5 mg twice daily plus allopurinol 300 mg once daily. Three people (10%) allocated to the colchicine plus allopurinol group who did not take allopurinol were included in the colchicine-only group for analysis. In the first year there was no significant difference between treatments in recurrent attacks of gout (10/33 [30%] with colchicine alone v 5/26 [19%] with colchicine plus allopurinol; difference reported as not significant; P value not reported). The primary outcome for the RCT comparing allopurinol versus febuxostat was a serum urate of <0.36 mmol/L at each of the last three monthly visits. Both doses of febuxostat significantly increased the proportion of people achieving the primary end point compared with allopurinol (53/251 [21%] with allopurinol v 136/255 [53%] with febuxostat 80 mg v 154/250 [62%] with febuxostat 120 mg; P <0.001 for allopurinol v febuxostat 80 mg and febuxostat 120 mg).

Clinical guide:

Many experts believe that allopurinol should not normally be started during an attack of gout. There is some evidence to support the usual practice of co-prescribing prophylactic drugs, such as colchicine, when starting urate-lowering medication. The focus of this review is the prevention of recurrent gout rather than reducing serum urate. It is not clear how effective xanthine oxidase inhibitors are at reducing the incidence of recurrent gout. If urate-lowering drugs are used, then the dose should be titrated upwards to achieve a target urate level of <0.36 mmol/L, which prevents crystal formation and promotes their dissolution. Febuxostat seems more effective than allopurinol at reducing serum urate, but does not result in a reduction in recurrent gout over the first year of treatment. Febuxostat might be an alternative for people who cannot tolerate allopurinol.

Substantive changes

Xanthine oxidase inhibitors New evidence added. Categorisation unchanged (Unknown effectiveness), as there remains insufficient evidence to judge the effects of this intervention.

[BMJ_1120_REF1] 1.Emmerson BT. The management of gout. N Engl J Med 1996;334:445–451. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF2] 2.Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977;20:895–900. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF3] 3.Kim KY, Schumacher HR, Hunsche E, et al. A literature review of the epidemiology and treatment of acute gout. Clin Ther 2003;25:1593–1616. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF4] 4.Harris CM, Lloyd DC, Lewis J. The prevalence and prophylaxis of gout in England. J Clin Epidemiol 1995;48:1153–1158. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF5] 5.Abbott RD, Brand FN, Kannel WB, et al. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol 1988;41:237–242. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF6] 6.Choi HK, Atkinson K, Karlson EW, et al. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med 2004;350:1093–1103. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF7] 7.Bieber JD, Terkeltaub RA. Gout: on the brink of novel therapeutic options for an ancient disease. Arthritis Rheum 2004;50:2400–2414. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF8] 8.Hochberg MC, Thomas J, Thomas DJ, et al. Racial differences in the incidence of gout. The role of hypertension. Arthritis Rheum 1995;38:628–632. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF9] 9.Klemp P, Stansfield SA, Castle B, et al. Gout is on the increase in New Zealand. Ann Rheum Dis 1997;56:22–26. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF10] 10.McGill NW. Gout and other crystal-associated arthropathies. Baillieres Best Pract Res Clin Rheumatol 2000;14:445–460. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF11] 11.Lin KC, Lin HY, Chou P. The interaction between uric acid level and other risk factors on the development of gout among asymptomatic hyperuricemic men in a prospective study. J Rheumatol 2000;27:1501–1505. [PubMed] [Google Scholar]

[BMJ_1120_REF12] 12.Schlesinger N, Baker DG, Schumacher HR Jr. Serum urate during bouts of acute gouty arthritis. J Rheumatol 1997;24:2265–2266. [PubMed] [Google Scholar]

[BMJ_1120_REF13] 13.Logan JA, Morrison E, McGill PE. Serum uric acid in acute gout. Ann Rheum Dis 1997;56:696–697. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF14] 14.Stewart OJ, Silman AJ. Review of UK data on the rheumatic diseases –4. Gout. Br J Rheumatol 1990;29:485–488. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF15] 15.Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med 1987;82:421–426. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF16] 16.Choi HK, Atkinson K, Karlson EW, et al. Alcohol intake and risk of incident gout in men: a prospective study. Lancet 2004;363:1277–1281. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF17] 17.Culleton BF. Uric acid and cardiovascular disease: a renal-cardiac relationship? Curr Opin Nephrol Hypertens 2001;10:371–375. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF18] 18.Bryan E. Are gout and increased uric acid levels risk factors for cardiac disease? In: Center for Clinical Effectiveness Series 2002: Aetiology. Clayton, Australia: Monash Institute of Health Services Research, 2002. [Google Scholar]

[BMJ_1120_REF19] 19.Choi HK, Curhan G, Choi Hyon K, et al. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ 2008;336:309–312. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF20] 20.Bellamy N, Downie WW, Buchanan WW. Observations on spontaneous improvement in patients with podagra: implications for therapeutic trials of non-steroidal anti-inflammatory drugs. Br J Clin Pharmacol 1987;24:33–36. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF21] 21.Yu TF, Gutman AB. Efficacy of colchicine prophylaxis in gout. Ann Intern Med 1961;55:179–192. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF22] 22.Gelber AC, Klag MJ, Mead LA, et al. Gout and risk for subsequent coronary heart disease. The Meharry-Hopkins Study. Arch Intern Med 1997;157:1436–1440. [PubMed] [Google Scholar]

[BMJ_1120_REF23] 23.Schlesinger N, Schumacher R, Catton M, et al. Colchicine for acute gout. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. 17054279 [Google Scholar]

[BMJ_1120_REF24] 24.Ahern MJ, Reid C, Gordon TP, et al. Does colchicine work? The results of the first controlled study in acute gout. Aust N Z J Med 1987;17:301–304. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF25] 25.Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare: twenty-four-hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum 2010;62:1060–1068. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF26] 26.Schlesinger N, Schumacher HR Jr. Gout: can management be improved? Curr Opin Rheumatol 2001;13:240–244. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF27] 27.Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila.) 2010;48:407–414. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF28] 28.Underwood M. Diagnosis and management of gout. BMJ 2006;332:1315–1319. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF29] 29.Janssens HJ, Lucassen PL, Van de Laar FA, et al. Systemic corticosteroids for acute gout. In: The Cochrane Library, Issue 3, 2010. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007. 18425920 [Google Scholar]

[BMJ_1120_REF30] 30.Man CY, Cheung IT, Cameron PA, et al. Comparison of oral prednisolone/paracetamol and oral indomethacin/paracetamol combination therapy in the treatment of acute goutlike arthritis: a double-blind, randomized, controlled trial. Ann Emerg Med 2007;49:670–677. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF31] 31.Janssens HJ, Janssen M, Van de Lisdonk EH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial. Lancet 2008;371:1854–1860. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF32] 32.Taylor CT, Brookes NC, Kelley KW. Corticotropin for acute management of gout. Ann Pharmacother 2001:35:365–368. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF33] 33.Sutaria, S, Katbamna, R, Underwood M. Effectiveness of interventions for the treatment of acute and prevention of recurrent gout: a systematic review. Rheumatology 2006;45:1422–1431. Search date 2005. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF34] 34.Garcia de la Torre I. Double-blind parallel study comparing tenoxicam and placebo in acute gouty arthritis. Invet Med Int 1987;14:92–97. [In Spanish] [Google Scholar]

[BMJ_1120_REF35] 35.Rubin BR, Burton R, Navarra S, et al. Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial. Arthritis Rheum 2004;50:598–606. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF36] 36.Schumacher HR Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. BMJ 2002;324:1488–1492. [DOI] [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF37] 37.Maccagno A, Di Giorgio E, Romanowicz A. Effectiveness of etodolac ("Lodine") compared with naproxen in patients with acute gout. Curr Med Res Opin 1991;12:423–429. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF38] 38.Lederman R. A double-blind comparison of etodolac (Lodine) and high doses of naproxen in the treatment of acute gout. Adv Ther 1990;7:344–354. [Google Scholar]

[BMJ_1120_REF39] 39.Altman RD, Honig S, Levin JM, et al. Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol 1988;15:1422–1426. [PubMed] [Google Scholar]

[BMJ_1120_REF40] 40.Lomen PL, Turner LF, Lamborn KR, et al. Flurbiprofen in the treatment of acute gout. A comparison with indomethacin. Am J Med 1986;80:134–139. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF41] 41.Fraser RC, Davis RH, Walker FS. Comparative trial of azapropazone and indomethacin plus allopurinol in acute gout and hyperuricaemia. J R Coll Gen Pract 1987;37:409–411. [PMC free article] [PubMed] [Google Scholar]

[BMJ_1120_REF42] 42.Non-steroidal anti-inflammatory drugs. In: Royal Pharmaceutical Society of Great Britain, eds. British National Formulary. Wallingford: Pharmaceutical Press, 2008:543–552. [Google Scholar]

[BMJ_1120_REF43] 43.Cheng TT, Lai HM, Chiu CK, et al. A single-blind, randomized, controlled trial to assess the efficacy and tolerability of rofecoxib, diclofenac sodium, and meloxicam in patients with acute gouty arthritis. Clin Ther 2004;26:399–406. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF44] 44.Willburger RE, Mysler E, Derbot J, et al. Lumiracoxib 400 mg once daily is comparable to indomethacin 50 mg three times daily for the treatment of acute flares of gout. Rheumatology 2007;46:1126–1132. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF45] 45.Anon. Gout in primary care. Drug Ther Bull 2004;42:37–40. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF46] 46.National Institute for Health and Clinical Excellence. Osteoarthritis. The care and management of osteoarthritis in adults. NICE Clinical Guideline CG 59. 2008. Available at http://www.nice.org.uk/CG59 (last accessed 18 April 2011). [Google Scholar]

[BMJ_1120_REF47] 47.Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum 2008;59:1540–1548. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF48] 48.Becker MA, Schumacher, HR Jr, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med 2005;353:2450–2461. [DOI] [PubMed] [Google Scholar]

[BMJ_1120_REF49] 49.Borstad GC, Bryant LR, Abel MP, et al. Colchicine for prophylaxis of acute flares when initiating allopurinol for chronic gouty arthritis. J Rheumatol 2004;31:2429–244. [PubMed] [Google Scholar]

[BMJ_1120_REF50] 50.Gibson T, Rodgers V, Potter C, et al. Allopurinol treatment and its effect on renal function in gout: a controlled study. Ann Rheum Dis 1982;41:59–65. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Gout

Martin Underwood

Roles

Abstract

Introduction

Methods and outcomes

Results

Conclusions

Key Points

About this condition

Definition

Table 1.

Incidence/ Prevalence

Aetiology/ Risk factors

Prognosis

Aims of intervention

Outcomes

Methods

Table.

Glossary

References

Colchicine (oral) for treating acute gout

Summary

Benefits and harms

Colchicine versus placebo:

Symptom severity

Adverse effects

Colchicine versus NSAIDs:

Colchicine versus corticosteroids:

Further information on studies

Comment

Clinical guide:

Substantive changes

Corticosteroids

Summary

Benefits and harms

Corticosteroids versus placebo:

Corticosteroids versus NSAIDs:

Symptom severity

Adverse effects

Corticosteroids versus colchicine:

Colchicine versus corticotropin:

Further information on studies

Comment

Clinical guide:

Substantive changes

Corticotropin (adrenocorticotrophic hormone)

Summary

Benefits and harms

Corticotropin (adrenocorticotrophic hormone [ACTH]) versus placebo:

Corticotropin versus NSAIDs:

Corticotropin versus corticosteroids:

Further information on studies

Comment

Clinical guide:

Substantive changes

NSAIDs

Summary

Benefits and harms

NSAIDs versus placebo:

Symptom severity

Adverse effects

NSAIDs versus each other:

Symptom severity

Adverse effects

NSAIDs versus corticosteroids:

Further information on studies

Comment

NSAIDs versus each other:

Clinical guide:

Substantive changes

Advice to lose weight

Summary

Benefits and harms

Advice to lose weight:

Comment

Substantive changes

Advice to reduce alcohol intake

Summary