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Lesinurad Cuts Uric Acid in Refractory Gout

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Lesinurad Cuts Uric Acid in Refractory Gout 20 ARTHRITIS AUGUST 2011 • RHEUMATOLOGY NEWS Lesinurad Cuts Uric Acid in Refractory Gout Ninety percent of patients who remained on fore the end of this year, said Barry D. a uric acid transporter molecule in the Quart, Pharm.D., president of Ardea kidney that takes uric acid out of urine treatment for 28 weeks met the study’s target level. Biosciences, the San Diego–based com- and places it back into the blood. pany that is developing the drug. The study led by Dr. Perez-Ruiz en- BY MITCHEL L. ZOLER mg/day of lesinurad also appeared safe, The phase III study will likely focus on rolled patients who met the 1977 gout di- with no adverse effects or other safety the 200-mg and 400-mg/day dosages, as agnosis criteria of the American FROM THE ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY concerns seen during the limited treat- over time most patients appeared to re- Rheumatism Association (now the ment period reported, said Dr. Perez- spond to these lower dosages. American College of Rheumatology) LONDON – An investigational drug Ruiz, a rheumatologist at Hospital de “Almost no one needs 600 mg/day to and who had a serum uric acid level that boosts uric acid secretion led to sig- Cruces in Barakaldo, Spain. get a response,” Dr. Quart said in an in- greater than 6 mg/dL despite being on terview. a stable dose of 200-600 mg allopurinol Major Finding: After 4 weeks of treatment with a combination of 200-600 Although the current study used pa- for at least 6 weeks. mg/day lesinurad plus allopurinol and colchicine, 71%-87% of patients had tients’ serum uric acid levels of lower Patients were randomized to daily serum uric acid levels lower than 6 mg/dL, compared with 28% of patients than 6 mg/dL as the end point and did treatment with 200 mg, 400 mg, or 600 who were treated with allopurinol, colchicine, and placebo. not assess clinical features of gout, this mg of oral lesinurad or placebo. VITALS Data Source: A randomized, phase II study with 208 patients who were diag- end point is highly meaningful, said Dr. All patients also received a 0.5-mg or nosed with gout and whose serum uric acid levels remained above 6 mg/dL Maxime Dougados, professor of 0.6-mg daily dose of colchicine, and they despite at least 6 weeks on steady treatment with 200-600 mg/day of allo- rheumatology at René Descartes Uni- all also remained on the dosage of al- purinol. versity in Paris. lopurinol that they were taking at entry Disclosures: The study was funded by Ardea Biosciences, which is developing Gout treatment guidelines developed into the study. lesinurad. Dr. Perez-Ruiz said that he has had financial relationships with by the European League Against After 4 weeks on treatment, the per- Ardea, Menarini, and Novartis. Dr. Dougados said he has been a consultant Rheumatism (EULAR) emphasize “the centage of patients whose serum uric for and received research support from Roche. importance of treating patients to a tar- acid level had fallen below 6 mg/dL was get serum uric acid of less than 6 28% in the 72 placebo patients, and 71%, mg/dL,” commented Dr. Dougados. 76%, and 87% in the three lesinurad nificant cuts in serum uric acid levels dur- The drug worked equally well in pa- treatment groups, which each contained ing 4 weeks of treatment in a phase II tients with normal renal function (a New Drugs Increase Excretion 42-48 patients. study of 208 patients with allopurinol-re- glomerular filtration rate of at least 90 “Until now, we have drugs that decrease The difference in the percentage of re- fractory gout. mL/min per 1.73 m2) and in those with uric acid synthesis, but we have not re- sponding patients in each of the three In addition, among 30 patients who re- mildly impaired renal function, with cently had any drugs to increase excre- treatment arms was statistically signifi- mained on the uricosuric agent lesinurad GFRs of 50-89 mL/min per 1.73 m2, Dr. tion,” Dr. Dougados observed, adding cant, compared with the placebo group. for 28 weeks in an extension phase, 27 Perez-Ruiz reported in a presentation at that “Now we have a new drug to in- “Lesinurad produced rapid and sus- patients (90%) reached the study’s target the meeting. crease excretion, and that is very impor- tained reductions in uric acid levels when level of serum uric acid (lower than 6 tant because allopurinol is often not suf- added on to allopurinol in patients who mg/dL), according to Dr. Fernando Phase III Trial to Start This Year ficient to achieve the target serum uric were not adequately responding to al- Perez-Ruiz. Based on these promising early results, acid level.” lopurinol alone,” Dr. Perez-Ruiz con- Treatment with dosages of 200-600 a phase III trial of lesinurad will start be- Lesinurad works by inhibiting URAT1, cluded. ■ To Reverse Metabolic Syndrome, Take Gout by the Horns BY SHARON WORCESTER same NHANES population was high (nearly 63%), fat, which can increase insulin resistance. Therefore, it compared with 25% in those without a gout diagnosis. is important to advise patients to reduce intake of high- atients presenting with hyperuricemia or gout The prevalence was even higher (83%) among those purine foods, but also to avoid high-fat foods and the Pshould be evaluated for metabolic syndrome, and with a more stringently defined gout diagnosis (specif- wrong kinds of carbohydrates. any recommendations regarding dietary changes and ically, those on urate-lowering therapy), Dr. Edwards About 40% of their diet should be complex carbo- medical treatment for gout should take into consider- noted (Arthritis Rheum. 2007;57:109-15). hydrates, no more than 30% should be proteins, and no ation the potential benefits of urate reduction, ac- As with hyperuricemia, the investigators concluded more than 30% should be mono- or polyunsaturated cording to Dr. N. Lawrence Edwards. that the prevalence of metabolic syndrome is high in fats, he said. Both hyperuricemia and gout are independent risk individuals with gout, and that, As for medical treatment factors for metabolic syndrome and its individual com- given the serious complications For gout patients, about 40% of considerations, it is important ponents, said Dr. Edwards, professor of medicine at the that can be associated with to keep in mind the mecha- University of Florida, Gainesville. metabolic syndrome, the con- their diet should be complex nisms of hyperuricemia as it re- In a 2007 study looking at the prevalence of meta- dition should be recognized and carbohydrates, no more than lates to insulin resistance, he bolic syndrome in nearly 8,700 patients with hyper- taken into account when clini- added. uricemia from the NHANES (National Health and Nu- cians plan the long-term treat- 30% should be proteins, and no In patients who are hyper- trition Examination Survey) III database, the prevalence ment of patients with gout. more than 30% should be triglyceridemic, for example, of metabolic syndrome increased in tandem with in- The findings of these two niacin is a commonly used creasing levels of serum urate, and the increase per- studies support a pathogenic mono- or polyunsaturated fats. drug. sisted across subgroups stratified by age, sex, alcohol overlap between metabolic syn- However, niacin can elevate intake, body mass index, hypertension, and diabetes drome and gout, and underscore the importance of uric acid levels “by quite a margin” of 1.5-2.5 mg/dL. (Am. J. Med. 2007;120:442-7). evaluating gout patients for the syndrome, Dr. Edwards Conversely, fenofibrate can also be used to treat hy- The investigators found that the prevalence of meta- said. pertriglyceridemia, and can lower the levels by a simi- bolic syndrome (defined using both original and revised “You see a lot of patients coming in, and they haven’t lar margin. National Cholesterol Education Program Adult Treat- had fasting glucoses performed, blood pressures may “So just making that switch might make a pretty sub- ment Panel III criteria) was 19% in those with uric acid be a little out of control, and weight is certainly out of stantial difference,” Dr. Edwards said. levels less than 6 mg/dL, 36% in those with 8.0-8.9 control,” he noted. In patients who are being treated for hypertension, mg/dL, 62% for 9.0-9.9 mg/dL, and 71% for levels of “We need to look at these patients much more seri- keep in mind that hydrochlorothiazide is associated 10 mg/dL or greater. ously than if they only have gout; they need a full-court with elevated uric acid levels, and consider switching to Physicians should recognize that metabolic syn- press on all of their metabolic problems and not just the angiotensin receptor blocker losartan in those in drome occurs frequently in patients with hyper- their uric acid.” whom hydrochlorathiazide is used solely for hyper- uricemia, and should be treated to prevent serious com- Dietary recommendations that consist of the stan- tension control and not for fluid control, as losartan has plications, they concluded. dard advice to avoid foods high in purines are not suf- uric acid lowering effects, he said. In a related study, the prevalence of metabolic syn- ficient. Patients will often cut out meat and shellfish, Dr. Edwards had no disclosures relevant to his pre- drome in patients with doctor-diagnosed gout from the but replace those with foods high in carbohydrates and sentation. ■ Pages 20a—20dŅ.
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