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Annals of Internal Medicine Jan 2017The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout.
DESCRIPTION
The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout.
METHODS
Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms.
TARGET AUDIENCE AND PATIENT POPULATION
The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout.
RECOMMENDATION 1
ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence).
RECOMMENDATION 2
ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence).
RECOMMENDATION 3
ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence).
RECOMMENDATION 4
ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).
Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Comparative Effectiveness Research; Gout; Gout Suppressants; Humans; Life Style; Recurrence; Uric Acid; Withholding Treatment
PubMed: 27802508
DOI: 10.7326/M16-0570 -
Lancet (London, England) Nov 2020Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European... (Randomized Controlled Trial)
Randomized Controlled Trial
Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial.
BACKGROUND
Febuxostat and allopurinol are urate-lowering therapies used to treat patients with gout. Following concerns about the cardiovascular safety of febuxostat, the European Medicines Agency recommended a post-licensing study assessing the cardiovascular safety of febuxostat compared with allopurinol.
METHODS
We did a prospective, randomised, open-label, blinded-endpoint, non-inferiority trial of febuxostat versus allopurinol in patients with gout in the UK, Denmark, and Sweden. Eligible patients were 60 years or older, already receiving allopurinol, and had at least one additional cardiovascular risk factor. Those who had myocardial infarction or stroke in the previous 6 months or who had severe congestive heart failure or severe renal impairment were excluded. After a lead-in phase in which allopurinol dose was optimised towards achieving a serum urate concentration of less than 0·357 mmol/L (<6 mg/dL), patients were randomly assigned (1:1, with stratification according to previous cardiovascular events) to continue allopurinol (at the optimised dose) or start febuxostat at 80 mg/day, increasing to 120 mg/day if necessary to achieve the target serum urate concentration. The primary outcome was a composite of hospitalisation for non-fatal myocardial infarction or biomarker-positive acute coronary syndrome; non-fatal stroke; or cardiovascular death. The hazard ratio (HR) for febuxostat versus allopurinol in a Cox proportional hazards model (adjusted for the stratification variable and country) was assessed for non-inferiority (HR limit 1·3) in an on-treatment analysis. This study is registered with the EU Clinical Trials Register (EudraCT 2011-001883-23) and ISRCTN (ISRCTN72443728) and is now closed.
FINDINGS
From Dec 20, 2011, to Jan 26, 2018, 6128 patients (mean age 71·0 years [SD 6·4], 5225 [85·3%] men, 903 [14·7%] women, 2046 [33·4%] with previous cardiovascular disease) were enrolled and randomly allocated to receive allopurinol (n=3065) or febuxostat (n=3063). By the study end date (Dec 31, 2019), 189 (6·2%) patients in the febuxostat group and 169 (5·5%) in the allopurinol group withdrew from all follow-up. Median follow-up time was 1467 days (IQR 1029-2052) and median on-treatment follow-up was 1324 days (IQR 870-1919). For incidence of the primary endpoint, on-treatment, febuxostat (172 patients [1·72 events per 100 patient-years]) was non-inferior to allopurinol (241 patients [2·05 events per 100 patient-years]; adjusted HR 0·85 [95% CI 0·70-1·03], p<0·0001). In the febuxostat group, 222 (7·2%) of 3063 patients died and 1720 (57·3%) of 3001 in the safety analysis set had at least one serious adverse event (with 23 events in 19 [0·6%] patients related to treatment). In the allopurinol group, 263 (8·6%) of 3065 patients died and 1812 (59·4%) of 3050 had one or more serious adverse events (with five events in five [0·2%] patients related to treatment). Randomised therapy was discontinued in 973 (32·4%) patients in the febuxostat group and 503 (16·5%) patients in the allopurinol group.
INTERPRETATION
Febuxostat is non-inferior to allopurinol therapy with respect to the primary cardiovascular endpoint, and its long-term use is not associated with an increased risk of death or serious adverse events compared with allopurinol.
FUNDING
Menarini, Ipsen, and Teijin Pharma Ltd.
Topics: Aged; Allopurinol; Cardiovascular Diseases; Denmark; Febuxostat; Female; Gout; Gout Suppressants; Hospitalization; Humans; Male; Prospective Studies; Sweden; Treatment Outcome; United Kingdom; Uric Acid
PubMed: 33181081
DOI: 10.1016/S0140-6736(20)32234-0 -
Rheumatology (Oxford, England) Jan 2018Colchicine is an ancient medication that is currently approved for the treatment of gout and FMF. However, colchicine has a wide range of anti-inflammatory activities,... (Review)
Review
Colchicine is an ancient medication that is currently approved for the treatment of gout and FMF. However, colchicine has a wide range of anti-inflammatory activities, and studies indicate that it may be beneficial in a variety of other conditions. This paper reviews the evidence for the well-established use of colchicine in gout, as well as several other rheumatic diseases. In addition, we highlight the potential benefit of colchicine in cardiac disease, including coronary artery disease in patients both with and without gout.
Topics: Cardiovascular Diseases; Colchicine; Gout; Gout Suppressants; Humans
PubMed: 29272515
DOI: 10.1093/rheumatology/kex453 -
Arthritis and Rheumatism Nov 2008To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
OBJECTIVE
To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.
METHODS
Subjects (n = 1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to < or = 2.0 mg/dl) renal function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.
RESULTS
Significantly (P < or = 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.
CONCLUSION
At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.
Topics: Adult; Aged; Allopurinol; Creatinine; Dose-Response Relationship, Drug; Double-Blind Method; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Middle Aged; Thiazoles; Treatment Outcome; Uric Acid
PubMed: 18975369
DOI: 10.1002/art.24209 -
CMAJ : Canadian Medical Association... Feb 2021
Topics: Anti-Inflammatory Agents, Non-Steroidal; Comorbidity; Gout; Gout Suppressants; Humans; Microscopy; Prevalence; Risk Factors; Synovial Fluid; Uric Acid
PubMed: 33526544
DOI: 10.1503/cmaj.201392 -
BMJ Clinical Evidence Mar 2015Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years. (Review)
Review
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 xanthine oxidase inhibitors to prevent gout in people with prior acute episodes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (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 21 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, non-steroidal anti-inflammatory drugs (NSAIDs), and xanthine oxidase inhibitors.
Topics: Gout; Gout Suppressants; Humans; Treatment Outcome
PubMed: 25789770
DOI: No ID Found -
American Family Physician Nov 2017
Review
Topics: Decision Support Systems, Clinical; Evidence-Based Medicine; Gout; Gout Suppressants; Humans; Practice Guidelines as Topic; Sensitivity and Specificity
PubMed: 29431386
DOI: No ID Found -
BMJ Clinical Evidence May 2011Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years. (Review)
Review
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.
Topics: Acute Disease; Adrenocorticotropic Hormone; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Gout; Gout Suppressants; Humans
PubMed: 21575286
DOI: No ID Found -
BMC Nephrology Jun 2022Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.
METHODS
MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events.
RESULTS
NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified.
CONCLUSIONS
Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function.
TRIAL REGISTRATION
This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12 November 2019.
Topics: Adult; Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Uric Acid
PubMed: 35739495
DOI: 10.1186/s12882-022-02850-3 -
The Korean Journal of Internal Medicine Jul 2022Effective management of gout includes the following: appropriate control of gout flares; lifestyle modifications; management of comorbidities; and long-term... (Review)
Review
Effective management of gout includes the following: appropriate control of gout flares; lifestyle modifications; management of comorbidities; and long-term urate-lowering therapy (ULT) to prevent subsequent gout flares, structural joint damage, and shortening of life expectancy. In addition to traditional treatments for gout, novel therapies have been introduced in recent years. Indeed, new recommendations for the management of gout have been proposed by various international societies. Although effective and safe medications to treat gout have been available, management of the disease has continued to be suboptimal, with poor patient adherence to ULT and failure to reach serum urate target. This review outlines recent progress in gout management, mainly based on the latest published guidelines, and specifically provides an update on efficient strategies for implementing treatment, efficacy and safety of specific medications for gout, and cardiovascular outcomes of ULT. In particular, we reviewed gout management approaches that can be applied to a Korean population.
Topics: Gout; Gout Suppressants; Humans; Hyperuricemia; Republic of Korea; Uric Acid
PubMed: 35811361
DOI: 10.3904/kjim.2022.036