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      Recent advances in management of gout

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      QJM
      Oxford University Press (OUP)

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          Abstract

          Incidence and prevalence of gout have markedly increased over the last few decades in keeping with the rise in prevalence of obesity and metabolic syndrome. Until recently, management of gout in patients with associated metabolic syndrome and comorbid illnesses such as renal impairment was difficult because of limited treatment options. However, significant progress has been made in the last few years, with introduction of new treatments such as interleukin-1 antagonists for management of acute gout, and febuxostat and pegloticase for chronic gout. The association of gout with alcohol, dietary purines and fructose ingestion has been confirmed in large prospective studies, thus enabling the clinician to now provide evidence-based advice to patients. Recent efficacy and safety data favour lower over higher doses of colchicine, and oral corticosteroids over non-steroidal anti-inflammatory drugs for patients with acute gout. Local ice therapy might help to differentiate gout from other forms of inflammatory arthritis, and supplementation with vitamin C help to reduce risk of gout. Several other drugs with rational mechanisms of action are in the pipeline, and likely to be introduced over the next few years. A new era has thus begun in the field of gout.

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          Most cited references66

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          Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

          Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Design Network meta-analysis. Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.
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            Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

            Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout. We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area. The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group). Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups. Copyright 2005 Massachusetts Medical Society.
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              Purine-rich foods, dairy and protein intake, and the risk of gout in men.

              Various purine-rich foods and high protein intake have long been thought to be risk factors for gout. Similarly, the possibility that the consumption of dairy products has a role in protecting against gout has been raised by metabolic studies. We prospectively investigated the association of these dietary factors with new cases of gout. Over a 12-year period, we prospectively examined the relationship between purported dietary risk factors and new cases of gout among 47,150 men who had no history of gout at base line. We used a supplementary questionnaire to ascertain whether participants met the American College of Rheumatology survey criteria for gout. Diet was assessed every four years by means of a food-frequency questionnaire. During the 12 years of the study, we documented 730 confirmed new cases of gout. The multivariate relative risk of gout among men in the highest quintile of meat intake, as compared with those in the lowest quintile, was 1.41 (95 percent confidence interval, 1.07 to 1.86; P for trend = 0.02), and the corresponding relative risk associated with seafood intake was 1.51 (95 percent confidence interval, 1.17 to 1.95; P for trend = 0.02). In contrast, the incidence of gout decreased with increasing intake of dairy products; the multivariate relative risk among men in the highest quintile, as compared with those in the lowest quintile, was 0.56 (95 percent confidence interval, 0.42 to 0.74; P for trend <0.001). The level of consumption of purine-rich vegetables and the total protein intake were not associated with an increased risk of gout. Higher levels of meat and seafood consumption are associated with an increased risk of gout, whereas a higher level of consumption of dairy products is associated with a decreased risk. Moderate intake of purine-rich vegetables or protein is not associated with an increased risk of gout. Copyright 2004 Massachusetts Medical Society
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                Author and article information

                Journal
                QJM
                QJM
                Oxford University Press (OUP)
                1460-2725
                1460-2393
                April 18 2012
                May 01 2012
                December 23 2011
                May 01 2012
                : 105
                : 5
                : 407-417
                Article
                10.1093/qjmed/hcr242
                22198943
                666408c2-e521-4e06-9042-d4c86a0b7dcb
                © 2012
                History

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