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Press Release: Savient Reports Additional Positive Trial Data for Secondary Endpoints from Puricase(R) (pegloticase) Phase 3 Studies
Quote:
EAST BRUNSWICK, N.J., Feb 04, 2008; Savient Pharmaceuticals, Inc. (NASDAQ:SVNT), today announced additional positive results for secondary efficacy endpoints in the two replicate Phase 3 studies for Puricase(R) (pegloticase) for treatment-failure gout. Results were favorable for the treatment effect on clinical outcomes assessed by the reduction in the number of tender and swollen joints, and in improvement in Patient Reported Outcomes (PRO) as measured by Short Form-36 (SF-36) and the Health Assessment Questionnaire - Disability Index (HAQ-DI). These endpoints were assessed in a pre-specified pooled analysis from the two replicate studies and are reported for the Intent-to-Treat population. The improvement reported in these outcomes was clinically meaningful as determined by the pre-specified definitions.
The company previously reported that pegloticase had met the pre-specified primary efficacy endpoint, i.e. normalization of plasma uric acid for every two week and every four week dose administration, independently, in each of the two Phase 3 studies. In addition, the 8 mg every two week dose arm attained statistical significance versus placebo in the pre-specified pooled analysis, a secondary endpoint, in the proportion of patients who had a "complete response" for the elimination of gout tophi. The treatment effect of pegloticase on gout flares, another secondary endpoint, was reported as a favorable numerical trend in both treatment arms versus placebo, but neither treatment arm attained significance. The assessment of safety across the two Phase 3 studies was reported to be favorable and to have shown that the only adverse safety signal was the occurrence of infusion reactions. Seven patients (2/85 in the Q2 week arms, 5/84 in the Q4 week arms) had a total of 11 severe infusion reactions (muscle cramps, back or chest pain). Approximately 25 percent of all patients in the Q2 and Q4 treatment arms experienced a mild or moderate infusion reaction.
Following on this previously reported data, additional analysis showed statistical significance for both the every two week and every four week treatment arms versus placebo was achieved for:
-- a reduction in the number of tender and swollen joints
-- a reduction in the number of tender joints
-- an improvement in the clinician's global assessment (a 10 cm Visual Analog Scale)
For both treatment groups, the degree of improvement was greater for patients defined as plasma uric acid responders than for non-responders, but uric acid non-responders appeared to show improvement versus placebo as well. Further analysis of this finding is ongoing.
Two Patient Reported Outcomes instruments were employed in the pegloticase program, Short Form-36 (SF-36) and the Health Assessment Questionnaire - Disability Index (HAQ-DI), which have been used extensively in Rheumatology studies to assess clinically meaningful change in various rheumatic diseases. The results of the Phase 3 trials show that in the pre-specified pooled analysis, both treatment arms attained statistical significance for improvement versus placebo for the SF-36 physical component scores. The Arthritis-Specific Health Index form SF-36 also demonstrated statistically significant improvement versus placebo for both treatment arms and again showed that even the plasma uric acid non-responders had improvement versus placebo. The SF-36 bodily pain scale also demonstrated statistical significance for both treatment arms versus placebo and also showed that the plasma uric acid non-responders appeared to improve but only about half as well as the responders.
The results of the HAQ-DI assessment on arthritis pain showed statistically significant improvement versus placebo for the Q2 week dose group. The patient's own assessment of their overall functioning, a component of the HAQ-DI, showed that both treatment arms attained statistically significant improvement versus placebo.
"These results provide valuable evidence of clinical benefit in our upcoming regulatory submissions and are expected to be presented in full detail in future scientific forums and in peer-reviewed publications," stated Zeb Horowitz, M.D., Sr. VP and Chief Medical Officer. "The strength of the evidence from the two GOUT trials has the potential to change the way physicians and patients view treatment-failure gout, a view currently centered almost exclusively on the unsuccessful control of uric acid and the acute symptomatic relief of painful gout flares, gradually leading to increasingly advanced disease. In light of the pegloticase data, gout treatment-failure patients and their physicians have reason to hope for a better treatment option."
The company is scheduled to have a pre-BLA meeting with the reviewing division of the U.S. Food and Drug Administration (FDA) on April 17, 2008 and plans to file the BLA with the FDA as soon as practicable following the pre-BLA meeting based on the positive results from its Phase 3 trials.
Press Release:
February 6, 2008 FDA Takes Action to Stop the Marketing of Unapproved Injectable Drugs Containing Colchicine
Quote:
The U.S. Food and Drug Administration today announced its intention to take enforcement action against companies marketing unapproved injectable colchicine, a drug used to treat gout.
Colchicine is a highly toxic drug that can easily be administered in excessive doses, especially when given intravenously. There is a narrow margin between an effective dose of the drug and a toxic dose that can result in serious health risks, including death. The FDA is aware of 50 reports of adverse events associated with the use of intravenous colchicine, including 23 deaths. Potentially fatal effects include low blood cell counts, cardiac events, and organ failure.
"Today's action supports our ongoing efforts to end the marketing of unapproved drugs with serious health risks," said Janet Woodcock, M.D., FDA's deputy commissioner for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research (CDER). "Such products put consumers' health and sometimes their very lives at grave risk. It is a priority that these products be removed from the market."
Individuals and companies must stop making these products within 30 days and stop shipping the product within 180 days or face regulatory action which could include seizure, injunction or other legal action deemed appropriate by the agency. After these dates, all injectable colchicine drug products must have FDA approval to be manufactured or shipped interstate.
In June 2006, the FDA began taking action against marketed unapproved drugs. That effort seeks to ensure that all drug products marketed in the United States are shown, through the drug approval process, to be safe and effective and to meet appropriate standards for manufacturing and labeling. The agency published a Compliance Policy Guide (CPG) in June 2006 that describes the FDA's risk-based enforcement approach to marketed unapproved drugs. This represents the seventh action taken by the agency against companies that market and sell unapproved drugs since issuing its CPG.
"Until recently, there was one manufacturer of unapproved injectable colchicine, and that firm has ceased manufacturing the product," said Deborah Autor, director of the FDA's Office of Compliance, CDER. "This serves as the agency's warning that firms wishing to make injectable colchicine in the future must not manufacture the product until they apply for and are granted approval by the FDA to do so."
In addition to being manufactured by pharmaceutical companies, injectable colchicine products are sometimes formulated on a smaller scale by compounding pharmacies, often for use in the treatment of back pain. Three of the deaths from intravenous colchicine occurred in March and April of 2007 and were associated with the use of compounded colchicine that, due to an error in preparation, was eight times more potent than the amount stated on the label. The FDA has not approved colchicine in any dosage form for the treatment of back pain. In May 2007, the FDA informed all health care professionals about these deaths associated with compounded injectable colchicine products. The FDA's policy on pharmacy compounding is stated in a CPG on pharmacy compounding.
This action does not affect colchicine products that are dispensed in tablet form and are frequently used to prevent gout attacks.
Press Releases: COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE SUMMARY OF POSITIVE OPINION*
for ADENURIC
International Nonproprietary Name (INN): febuxostat
European Medicines Agency
Pre-Authorisation Evaluation of Medicines for Human Use
Quote:
On 21 February 2008 the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion,** recommending to grant a marketing authorisation for the medicinal product Adenuric, 80 mg and 120 mg, film-coated tablets intended for treatment of chronic hyperuricaemia in gout patients. The applicant for this medicinal product is Ipsen Manufacturing Ireland Limited.
The active substance of Adenuric is febuxostat, a medicinal product against gout and inhibits uric acid production (ATC Code MO4AA03); febuxostat is a non-purine selective inhibitor of xanthine oxidase.
The benefits with Adenuric are its potency to reduce serum urate. The most common side effects are liver function abnormalities, diarrhoea, headache, nausea and rash. In the clinical trials serious cardiovascular adverse events were the main safety concern.
A pharmacovigilance plan for Adenuric, as for all medicinal products, will be implemented as part of the marketing authorisation.
The approved indication is: “treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history or presence of, tophus and/or gouty arthritis)”.
Detailed recommendations for the use of this product will be described in the Summary of Product Characteristics (SPC) which will be published in the European Public Assessment Report (EPAR) and will be available in all official European Union languages after the marketing authorisation has been granted by the European Commission.
The CHMP, on the basis of quality, safety and efficacy data submitted, considers that there is a favourable benefit to risk balance for Adenuric and therefore recommends the granting of the marketing authorisation.
Press release EMEA recommends marketing authorisation of Ipsen’s Adenuric® (febuxostat) for the treatment of chronic hyperuricaemia in gout
Adenuric® represents the first major treatment of gout for more than forty years
Quote:
Paris (France), 21 February 2008 - Ipsen (Euronext: FR0010259150; IPN) announced today
that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines
Agency (EMEA) provided a positive opinion for Adenuric® (febuxostat) 80 mg and 120 mg
tablets for the treatment of chronic hyperuricaemia in gout and recommended it for marketing
authorisation. The CHMP recommendation will now be forwarded to the European Commission
for final marketing approval, which typically occurs within 60 to 90 days. Following marketing
approval, Adenuric® will become, since 1964, the first significant treatment alternative for chronic
hyperuricaemia available to gout patients.
Adenuric® is to be indicated for the treatment of chronic hyperuricaemia for conditions in which
urate deposition has already occurred (including a history, or presence of, tophus and/or gouty
arthritis). The detailed recommendations for the use of this product will be described in the
Summary of Product Characteristics (SPC), to be made available after the medication receives
marketing authorisation from the European Commission.
Once the product receives its marketing authorisation and its price is agreed, Febuxostat will be
marketed by Ipsen in France under the brand name Adenuric®. Outside France, the
commercialisation of the product will be partnered.
Jean-Luc Bélingard, Chairman and Chief Executive Officer of Ipsen, said, “We are very proud to
receive this positive opinion for Adenuric® from the EMEA, and look forward to bringing this new
molecule to market, pending European Commission approval. This innovative drug pioneers the
first major treatment of gout for more than 40 years. It confirms Ipsen’s ability to continue to
bring to the market important new treatment options for severely debilitating diseases.”
About Adenuric® (febuxostat)
Gout, a particularly painful type of arthritis, is the most frequent arthritis in men. It is caused by elevated
levels of uric acid in the body: hyperuricaemia. Febuxostat, an oral, once-daily medication, is a novel nonpurine,
selective inhibitor of xanthine oxidase studied for its effects on lowering levels of serum uric acid
(sUA) in patients with gout. Febuxostat is licensed to Ipsen for Europe from Teijin Pharma Limited, Tokyo.
The EU submission includes two of the largest industry sponsored studies to date studying treatment of
chronic gout patients. The goal of chronic gout treatment is per EULAR guidelines (European League
Against Rheumatism) to reduce and maintain sUA levels below 6 mg/dL. Febuxostat demonstrated
superior ability to lower and maintain in patients, serum uric acid at a level inferior to 6 mg/dl compared to
conventionally used doses of allopurinol (febuxostat 80 and 120 mg: 51 & 63 % resp. vs. allopurinol: 22%).
In addition, one phase III study showed that gout patients with mild to moderate renal impairment (serum
2/2
creatinine >1.5 - ≤2.0 mg/dl) had response rate of 44 and 45 % respectively with febuxostat 80 and 120
mg.
In 2003, Ipsen entered into a Research and Development partnership with Teijin Pharma Limited, the core
company of Teijin Group’s pharmaceutical and home healthcare business. The Teijin group is a Japanese
industrial conglomerate specialising in the businesses of fibres, films, plastics and information technology
(IT) as well as pharmaceuticals and home healthcare. This partnership covers the development and
subsequent commercialisation of four of Ipsen’s products by Teijin Pharma in Japan and the development
and marketing by Ipsen in Europe (i.e. European Union and Russia) of febuxostat, a product owned by
Teijin Pharma and known as TMX-67.
The BBC are reporting: Gene 'linked to higher gout risk'
A reason why millions worldwide fall prey to the painful joint condition gout may have been uncovered.
Quote:
A rise in UK gout cases has been blamed on increasingly unhealthy lifestyles.
However, genetic analysis of more than 12,000 people, published in the journal Nature Genetics, has found that a gene variant may also raise the risk.
Researchers at the MRC Human Genetics Unit, in Edinburgh, said the gene, and the protein it controls, might one day be targeted by new gout drugs.
In a healthy body, uric acid, a waste product found in the blood, is removed by the kidneys and passes out of the body in urine.
However, in some people the kidney cannot get rid of it properly and it builds up in the blood, forming crystals in the joints, leading to inflammation, stiffness and pain.
Various food types have been blamed, with the consensus that diets rich in refined sugars, protein and alcohol increase the risk.
Many thousands of people have a diet which appears to increase the risk of gout, but far fewer actually develop the illness.
Now scientists at the MRC Human Genetics Unit may have worked out why that is.
The gene variation they found, in the SLC2A gene, appears to make it harder for the body to remove uric acid from the blood.
Professor Alan Wright, who led the research, said: "The gene is a key player in determining the efficiency of uric acid transport across the membranes of the kidney."
His colleague Harry Campbell said: "Some people will have higher or lower risk of gout depending on the form of the gene they inherited.
"This discovery may allow better diagnostic tools for gout to be developed."
At the moment, drug treatment for patients is limited.
Although gout is a disease more usually found in a historical textbook, it is estimated that one million people in the UK suffer from it in some form.
Professor Stuart Ralston, from the British Society for Rheumatology, said that he often came across patients whose lifestyles did not fit the traditional view of over-consumption.
"Until recently you would associate gout with boozing and rich food, but there are plenty of other patients who are quite abstemious. This might be a genetic marker for gout risk.
"What is exciting is that it could be a target for new gout drugs."
Dr Andrew Bamji, president of the British Society for Rheumatology, said that the research supported a recent study which suggested that too many sugary soft drinks could trigger gout.
He said: "It appears that this gene also plays a role in the control of levels of fructose sugar in the body, which would explain the finding that soft drinks were linked to attacks."
Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200–500 M) compared with other mammals (3–120 M)1. About 70% of daily urate disposal occurs via the kidneys, and in 5–25% of the human population, impaired renal excretion leads to hyperuricemia2. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7–5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter3, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.
Press release: Adenuric® (febuxostat) receives marketing authorisation
in the European Union
Adenuric® represents the first major treatment of chronic hyperuricemia
in gout for more than forty years
Quote:
Paris (France), 5 May 2008 – Ipsen (Euronext: FR0010259150; IPN) today announced that
the European Commission granted marketing authorisation for Adenuric® (febuxostat) for the
treatment of chronic hyperuricaemia in gout. Adenuric® thus pioneers the first major
treatment alternative for gout, a severe debilitating disease, for more than 40 years.
"Recent surveys confirm that management of gout is often suboptimal, with less than half of
patients receiving appropriate lifestyle advice or urate lowering treatment" said Michael
Doherty, Professor of Rheumatology at the University of Nottingham (UK) and Co-chair of
the 2006 EULAR Task Force for the Recommendations on Diagnosis and Management of
Gout. "Recent European (EULAR) Recommendations emphasise the aim of "cure" by
lowering serum urate levels below the saturation point for crystal formation. For some
patients, the existing urate lowering therapies have limitations in terms of suitability or side
effects. The availability of a new effective therapy that allows the therapeutic target to be
achieved will improve the physicians armamentarium and ultimately benefit the population of
patients with gout."
Adenuric® (febuxostat) 80 mg and 120 mg tablets are indicated for the treatment of chronic
hyperuricaemia for conditions in which urate deposition has already occurred (including a
history, or presence of, tophus and/or gouty arthritis).
Adenuric® will be marketed by Ipsen in France. Outside France, the commercialisation of the
product will be partnered.
Here's a picture of a gouty ankle I did an arthroscope on. This is fairly representative of what the entire ankle joint looked like.
It was so classic I wanted to share it with you.
Steve
__________________
DrSArbes
Fellow American College of Foot & Ankle Surgeons
Board Certified Foot & Ankle Surgery, ABPS
Adjunct Professor OCPM
Green Bay, Wisconsin, USA
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Long-term Cardiovascular Mortality Among Middle-aged Men With Gout
Eswar Krishnan, MD, MPH; Kenneth Svendsen, MS; James D. Neaton, PhD; Greg Grandits, MS; Lewis H. Kuller, MD; for the MRFIT Research Group Arch Intern Med. 2008;168(10):1104-1110.
Quote:
Background There are limited data available on the association of gouty arthritis (gout) in middle age with long-term cardiovascular disease (CVD) mortality.
Methods We performed a 17-year follow-up study of 9105 men, aged 41 to 63 years and at above-average risk for coronary heart disease, who were randomized to the Multiple Risk Factor Intervention Trial and who did not die or have clinical or electrocardiographic evidence of coronary artery disease during the 6-year trial. Risk of CVD death and other causes subsequent to the sixth annual examination associated with gout was assessed by means of Cox proportional hazards regressions.
Results The unadjusted mortality rates from CVD among those with and without gout were 10.3 per 1000 person-years and 8.0 per 1000 person-years, respectively, representing an approximately 30% greater risk. After adjustment for traditional risk factors, use of diuretics and aspirin, and serum creatinine level, the hazard ratio (gout vs no gout) for coronary heart disease mortality was 1.35 (95% confidence interval [CI], 1.06-1.72). The hazard ratio for death from myocardial infarction was 1.35 (95% CI, 0.94-1.93); for death from CVD overall, 1.21 (95% CI, 0.99-1.49); and for death from any cause, 1.09 (95% CI, 1.00-1.19) (P = .04). The association between hyperuricemia and CVD was weak and did not persist when analysis was limited to men with hyperuricemia without a diagnosis of gout.
Conclusion Among middle-aged men, a diagnosis of gout accompanied by an elevated uric acid level imparts significant independent CVD mortality risk.
Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial
Dr Hein JEM Janssens MD, Matthijs Janssen PhD, Eloy H van de Lisdonk PhD, Prof Piet LCM van Riel PhD and Prof Chris van Weel PhD The Lancet Volume 371, Issue 9627, 31 May 2008-6 June 2008, Pages 1854-1860
Quote:
Background
Non-steroidal anti-inflammatory drugs and colchicine used to treat gout arthritis have gastrointestinal, renal, and cardiovascular adverse effects. Systemic corticosteroids might be a beneficial alternative. We investigated equivalence of naproxen and prednisolone in primary care.
Methods
We did a randomised clinical trial to test equivalence of prednisolone and naproxen for the treatment of monoarticular gout. Primary-care patients with gout confirmed by presence of monosodium urate crystals were eligible. 120 patients were randomly assigned with computer-generated randomisation to receive either prednisolone (35 mg once a day; n=60) or naproxen (500 mg twice a day; n=60), for 5 days. Treatment was masked for both patients and physicians. The primary outcome was pain measured on a 100 mm visual analogue scale and the a priori margin for equivalence set at 10%. Analyses were done per protocol and by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN14648181.
Findings
Data were incomplete for one patient in each treatment group, so per-protocol analyses included 59 patients in each group. After 90 h the reduction in the pain score was 44·7 mm and 46·0 mm for prednisolone and naproxen, respectively (difference 1·3 mm; 95% CI −9·8 to 7·1), suggesting equivalence. The difference in the size of change in pain was 1·57 mm (95% CI −8·65 to 11·78). Adverse effects were similar between groups, minor, and resolved by 3 week follow-up.
Interpretation
Oral prednisolone and naproxen are equally effective in the initial treatment of gout arthritis over 4 days.
Press Release: Ardea Biosciences' Advances RDEA806 Into Phase 2a Proof-of-Concept Study for Gout
Quote:
Ardea Biosciences, Inc. (Nasdaq: RDEA) today announced that it has received regulatory approval to begin a Phase 2a proof-of-concept clinical trial evaluating RDEA806 in gout patients with hyperuricemia. Gout, also known as metabolic arthritis, is a painful and debilitating disease caused by abnormally elevated levels of uric acid in the blood stream, and is the most common form of inflammatory arthritis in men over 40. The Company also announced that gout specialist, Dr. Fernando Perez-Ruiz in Spain, will be the newest member of its inflammatory disease scientific advisory board (SAB).
Ardea previously announced the designation of RDEA594, a major metabolite of RDEA806, the Company's lead human immunodeficiency virus (HIV) development compound, as its lead development candidate for the treatment of patients with gout. RDEA594 does not have antiviral activity, but is believed to be responsible for essentially all of the uric acid lowering effects seen with RDEA806. Uric acid lowering effects have been observed following administration of RDEA806 in Phase 1 and Phase 2 clinical trials that included over 100 subjects.
"The Phase 2a trial should allow us to confirm RDEA594's activity in the target population of patients with gout using its prodrug, RDEA806. Enrollment in the Phase 2a trial should begin shortly and we are on track to initiate a Phase 1 trial with RDEA594 in the second half of this year," said Barry D. Quart, PharmD, Ardea Biosciences' President and CEO. "We also are extremely pleased to add Dr. Fernando Perez-Ruiz to our inflammatory diseases SAB. Dr. Perez-Ruiz has extensive experience treating gout patients with drugs of the same class as RDEA594."
The Phase 2a randomized, double-blind, dose ranging, efficacy and safety trial will be conducted in academic medical centers in Europe and Canada. In this trial, we plan to evaluate the serum uric acid (sUA) level, pharmacokinetics, safety and tolerability of two different dose regimens of RDEA806 versus placebo in establishing normal sUA concentrations in gout patients with hyperuricemia (greater than or equal to 8.0 mg/dl). The primary efficacy endpoint is the proportion of subjects whose sUA level is less than 6.0 mg/dl following four weeks of treatment.
Dr. Fernando Perez-Ruiz is an Assistant Head of the Rheumatology Division at the Hospital de Cruces in Vizcaya, Spain. He received his medical degree from the Basque Country University in Bilbao, Spain, and a PhD from Barcelona University, Spain. Board-certified in Rheumatology, Dr. Perez-Ruiz is a member of the American College of Rheumatology and Spanish Society for Rheumatology and has collaborated with the European League Against Rheumatism (EULAR) Task Force for Gout and with the Outcome Measures for Rheumatic Arthritis Clinical Trials (OMERACT) group for chronic gout. He serves on the editorial boards of Arthritis Rheumatism (Care & Research), Bone Joint Spine, and Reumatologia Clinica and serves as a reviewer for more than 20 international journals. His research interests include crystal-induced arthritis, especially gout, but he has also investigated lupus, rheumatoid arthritis and fibromyalgia. Dr. Perez-Ruiz has published more than 80 articles on topics related to rheumatology, and most frequently to hyperuricemia and gout.
Here's a picture of a gouty ankle I did an arthroscope on. This is fairly representative of what the entire ankle joint looked like.
It was so classic I wanted to share it with you.
Steve
thanks for the picture
__________________
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Serum urate levels are often normal during acute gouty arthritis attacks, according to Dr. Naomi Schlesinger. In the study of 339 patients with acute gouty arthritis whose serum urate levels were measured, 29% of individuals on chronicallopurinol had a true-normal serum urate level, defined as 6 mg/dL or less. Among patients not on the hypouricemic agent, 11% had a true-normal serum urate level during their acute episode of gout.
Press Release: Regeneron's ARCALYST(R) (rilonacept) Reduced Incidence of Gout Flares by 81 Percent in a Phase 2 Study in Gout Patients Initiating Urate-Lowering Therapy
Proportion of patients experiencing gout flares reduced from 45.2 percent to 14.6 percent
Quote:
TARRYTOWN, N.Y--Sept. 3, 2008--Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) today announced that treatment with ARCALYST(R) (rilonacept), also known as IL-1 Trap, in a Phase 2 study of gout patients initiating therapy with allopurinol to lower their uric acid levels, produced a statistically significant reduction versus placebo in the incidence of gout flares. In this 83-patient, double-blind, placebo-controlled study, the mean number of flares per patient over the first 12 weeks of urate-lowering therapy was 0.79 with placebo and 0.15 with ARCALYST (p=0.0011), an 81 percent reduction. This was the primary endpoint of the study. All secondary endpoints also were met with statistical significance.
In the first 12 weeks of treatment, 45.2 percent of patients treated with placebo experienced a gout flare and, of those, 47.4 percent had more than one flare. Among patients treated with ARCALYST, only 14.6 percent experienced a gout flare (p=0.0037 versus placebo) and none had more than one flare. No serious drug-related adverse events were reported in patients receiving ARCALYST treatment. Injection-site reaction was the most commonly reported adverse event with ARCALYST treatment. Detailed data from the study will be presented at a future scientific conference.
This Phase 2 study evaluated the efficacy and safety of ARCALYST versus placebo in the prevention of gout flares induced by the initiation of uric acid-lowering drug therapy that is used to control gout. ARCALYST patients received an initial 320 milligram (mg) dose, followed by weekly doses of 160 mg. Gout is characterized by high blood levels of uric acid, a bodily waste product normally excreted by the kidneys. The uric acid can form crystals in the joints of the toes, ankles, knees, wrists, fingers, and elbows. Chronic treatment with uric acid-lowering medicines, such as allopurinol, is prescribed to eliminate the uric acid crystals and prevent reformation. During the first months of allopurinol therapy while uric acid blood levels are being reduced, the break up of the uric acid crystals can result in stimulation of inflammatory mediators, including interleukin-1 (IL-1), resulting in acute flares of joint pain and inflammation. These painful flares generally persist for at least five days. In this study a gout flare was defined as patient-reported acute joint pain that was deemed by the patient and/or investigator to require rescue treatment with an anti-inflammatory drug.
"These findings could be significant in the future management of patients with gout in that they address an impediment to successful long-term treatment. Allopurinol therapy is an important approach to lowering patients' high uric acid levels, which is the cause of their gout. However, the increased risk of painful gout flares over the first few months of initiation of uric acid-lowering therapy makes it difficult for patients to stick with treatment," said John Sundy, M.D., Ph.D., Division of Rheumatology, Department of Medicine, Duke University Medical Center. "Currently, colchicine or anti-inflammatory drugs are recommended for use to reduce the risk of gout flares in patients taking allopurinol, but these drugs may cause side effects and some patients do not tolerate them. The results from this study suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid gout flares, which could, in turn, improve patient outcomes."
"We are encouraged about the potential role of ARCALYST(R) (rilonacept) therapy in the treatment of gout. The results of this study, together with the findings of a previous small study of ARCALYST in patients with chronic, active gout, suggest that ARCALYST may provide utility in a number of different gout patient populations," stated George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories. "Based upon these results, we plan to initiate a Phase 3 clinical development program early next year with ARCALYST in the prevention of gout flares in patients initiating urate-lowering drug therapy. Studies in other gout settings are also planned."
Background
Hyperuricaemia, a highly heritable trait, is a key risk factor for gout. We aimed to identify novel genes associated with serum uric acid concentration and gout.
Methods
Genome-wide association studies were done for serum uric acid in 7699 participants in the Framingham cohort and in 4148 participants in the Rotterdam cohort. Genome-wide significant single nucleotide polymorphisms (SNPs) were replicated in white (n=11 024) and black (n=3843) individuals who took part in the study of Atherosclerosis Risk in Communities (ARIC). The SNPs that reached genome-wide significant association with uric acid in either the Framingham cohort (p<5·0×10−8) or the Rotterdam cohort (p<1·0×10−7) were evaluated with gout. The results obtained in white participants were combined using meta-analysis.
Findings
Three loci in the Framingham cohort and two in the Rotterdam cohort showed genome-wide association with uric acid. Top SNPs in each locus were: missense rs16890979 in SLC2A9 (p=7·0×10−168 and 2·9×10−18 for white and black participants, respectively); missense rs2231142 in ABCG2 (p=2·5×10−60 and 9·8×10−4), and rs1165205 in SLC17A3 (p=3·3×10−26 and 0·33). All SNPs were direction-consistent with gout in white participants: rs16890979 (OR 0·59 per T allele, 95% CI 0·52–0·68, p=7·0×10−14), rs2231142 (1·74, 1·51–1·99, p=3·3×10−15), and rs1165205 (0·85, 0·77–0·94, p=0·002). In black participants of the ARIC study, rs2231142 was direction-consistent with gout (1·71, 1·06–2·77, p=0·028). An additive genetic risk score of high-risk alleles at the three loci showed graded associations with uric acid (272–351 μmol/L in the Framingham cohort, 269–386 μmol/L in the Rotterdam cohort, and 303–426 μmol/L in white participants of the ARIC study) and gout (frequency 2–13% in the Framingham cohort, 2–8% in the Rotterdam cohort, and 1–18% in white participants in the ARIC study).
Interpretation
We identified three genetic loci associated with uric acid concentration and gout. A score based on genes with a putative role in renal urate handling showed a substantial risk for gout.
ScienceDaily are reporting: Drug Target for Gout? Gene SLC2A9 Is High-capacity Urate Transporter In Humans
Quote:
An international team of researchers led by Professors Mark Caulfield and Patricia Munroe, from the William Harvey Research Institute at Barts and The London School of Medicine and Dentistry with Chris Cheeseman at the University of Alberta in Canada and Kelle Moley at the University of Washington in USA, have shown that the SLC2A9 gene, which encodes a glucose transporter, is also a high-capacity urate transporter, and thus possibly a new drug target for gout.
Several urate transporters have already been identified but recently, using an approach called genome-wide association scanning, Caulfield and others found that some genetic variants of a human gene called SLC2A9 are more common in people with high serum urate levels than in people with normal levels. SLC2A9 encodes a glucose transporter (a protein that helps to move the sugar glucose through cell membranes) and is highly expressed in the kidney's main urate handling site. Professor Caulfield and his team investigated the possibility that the protein made by the SLC2A9 gene might be a urate transporter and tested whether genetic variations in SLC2A9 might be responsible for the association between serum urate levels and high blood pressure.
The team first expressed SLC2A9 in frog eggs, a type of cell that does not have its own urate transporter. They found that SLC2A9 transported urate about 50 times faster than glucose, and that glucose facilitated SLC2A9-mediated urate transport. Similarly, over expression of SLC2A9 in human embryonic kidney cells more than doubled their urate uptake. Conversely, when the researchers used a technique called RNA interference to reduce the expression of mouse SLC2A9 in mouse cells that normally makes this protein, urate transport was reduced.
Researchers then looked at two genetic variations within SLC2A9 that vary between individuals (so-called single polynucleotide polymorphisms) in nearly 900 men who had had their serum urate levels and urinary urate excretion rates measured. They found that certain genetic variations at these two sites were associated with increased serum urate levels and decreased urinary urate excretion. Finally, the researchers used a statistical technique called meta-analysis to look for an association between one of the SLC2A9 gene variants and blood pressure. In two separate meta-analyses that together involved more than 20,000 participants in several studies, there was no association between this gene variant and blood pressure.
Overall, these findings indicate that SLCA9 is a high capacity urate transporter, and suggest that this protein plays an important part in controlling serum urate levels. They provide confirmation that common genetic variants in SLC2A9 affect serum urate levels to a marked degree, although they do not show exactly which genetic variant is responsible for increasing serum urate levels. They also provide important new insights into how the kidneys normally handle urate and suggest ways in which this essential process may sometimes go wrong. The findings could eventually lead to new treatments for gout and possibly for other diseases that are associated with increased serum urate levels.
Professor Mark Caulfield said: "This MRC funded study shows how a team of international researchers can find a completely unsuspected mechanism for urate handling in the kidney. Such discoveries could pave the way for new medicines."
Background
Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man.
Methods and Findings
We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200–500 μM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 μM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case–control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size −0.12 mm Hg, 95% CI −0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size −0.03 mm Hg, 95% CI −0.39 to 0.31, p = 0.82).
Conclusions
This study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout.
Opportunities for improving medication use and monitoring in gout
Jasvinder A Singh, James M Hodges and Steven M Asch Ann Rheum Dis. Published Online First
Quote:
Purpose: Study patterns/predictors of medication use and laboratory monitoring, in gout.
Methods: In a cohort of veterans with diagnosis of gout, prescribed allopurinol, colchicine or probenecid, we examined quality-of-care by examining adherence to evidence-based recommendations, namely: (1) whether patients starting new allopurinol prescription (a) received continuous allopurinol; (b) received colchicine prophylaxis; (c) achieved target uric acid 6 mg/dl; and (2) if doses were adjusted for renal insufficiency. Logistic/Poisson regression examined association of socio-demographics, health care utilization and comorbidity with recommendations.
Results: Of the 643 gout patients receiving a new allopurinol prescription, 46% (297/643) had continuous allopurinol prescription, 10% (66/643) received colchicine prophylaxis and 20% (126/643) reached target uric acid of 6 mg/dl. During episodes of renal insufficiency, appropriate dose reduction/discontinuation of probenecid was done in 77% (24/31) episodes and of colchicine in 69% (36/52).
Multivariable regression showed higher outpatient utilization, more rheumatology care and lower comorbidity were associated with better quality-of-care: more rheumatology or primary care visits associated with less frequent allopurinol discontinuation, more total outpatient visit days or most frequent visits to rheumatology clinic with higher likelihood of receiving colchicine prophylaxis, and lower Charlson Comorbidity Index or more outpatient visit days with higher odds of reaching uric acid 6 mg/dl.
Conclusions: We found important variation in patterns of medication use and monitoring in gout patients, with suboptimal care. A concerted effort is needed to improve overall gout care.
In the past I posted a cause that is not often looked at. The cause is the development by an individual of gluten intolerance.
This can happen any time and at any age. The intolerance changes purine metabolism and the patient gets gout for the first time in their life.
I have seen it in a 70 year old lady after she had a hip replacement that took 5hours!
Intolerance can develop after a 'shock' to the system. It could be after surgery, a sudden death in the family, after a chest infection.... the list goes on.
If such an event has occurred, or they just developed gout out of the blue, it is worth investigating.
If it is the cause and they stick to the rules, they will not get gout and they will not need medications.
regards
musmed
The Following User Says Thank You to musmed For This Useful Post:
Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease. An ultrasound study
E. Filippucci, M. Gutierrez Riveros, D. Georgescu, F. Salaffi and W. Grassi Osteoarthritis and Cartilage (Article in Press)
Quote:
Objective
The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference.
Design
A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow.
Results
Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity = 99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity = 97.6%).
Conclusions
The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.
Objective
Several studies have suggested that higher serum uric acid levels lead to a lower risk of Parkinson's disease (PD) because uric acid exerts antioxidant effects on neurons. Our objective was to examine the relationship between gout and the risk of PD in persons age 65 years.
Methods
We conducted a population-based cohort study using the British Columbia Linked Health Database and PharmaCare data (i.e., prescription drug data for those age 65 years). We compared incidence rates of PD between 11,258 gout patients and 56,199 controls matched on age, sex, date of gout diagnosis, and length of medical record. Cox proportional hazards models were used to estimate the relative risk (RR) of PD, adjusting for age, sex, prior comorbid conditions, and use of diuretics and nonsteroidal antiinflammatory drugs.
Results
Over an 8-year median followup, we identified 1,182 new cases of PD. Compared with individuals without gout, the multivariate RR of PD among those with gout was 0.70 (95% confidence interval [95% CI] 0.59-0.83). In subgroup analyses, the inverse association was similarly present in both sexes and was evident among those who did not use diuretics (RR 0.66, 95% CI 0.54-0.81), but not among diuretic users (RR 0.80, 95% CI 0.58-1.10, P for interaction 0.35).
Conclusion
Our population-based data provide evidence for a protective effect of gout on the risk of PD and support the purported protective role of uric acid.
Medscape have just released this full text CME: Treating Chronic Gout: The Challenges of Lowering Serum Urate Levels
Slides + video. Link (free registration required)
Press Release: Arthritis Advisory Committee Recommends FDA Approval Of Febuxostat For The Treatment Of Hyperuricemia In Patients With Gout
25 Nov 2008
Quote:
Takeda Pharmaceutical Company Limited and its wholly-owned subsidiary, Takeda Global Research & Development Center, Inc., U.S., announced today that the Arthritis Advisory Committee of the U.S. Food and Drug Administration (FDA) recommended that the FDA approve febuxostat for the treatment of hyperuricemia in patients with gout. The vote was 12 to zero in favor of approval, with one panel member abstaining. The vote followed presentations by Takeda Global Research & Development Center, Inc., the FDA, and invited guest speakers. If approved in the United States by the FDA, febuxostat will be the first new treatment for the management of hyperuricemia associated with gout in more than 40 years.
The FDA will review the current new drug application for febuxostat and make its approval decision. The FDA's decision may or may not follow the Committee's recommendation.
"Today's vote by the Arthritis Advisory Committee, recommending approval of febuxostat for the treatment of hyperuricemia in patients with gout, is a positive step in bringing this new treatment to market," said Nancy Joseph-Ridge, MD, president, Takeda Global Research & Development, Inc., U.S. "Takeda is committed to developing innovative therapies that fulfill unmet treatment needs, and we believe febuxostat will represent an important new option for patients who suffer the debilitating effects of gout. In the coming months, we will work with the FDA to complete their review, including the design of post-marketing studies."
Febuxostat is a potent non-purine, selective inhibitor of xanthine oxidase, which was studied for its ability to lower levels of serum uric acid in patients with hyperuricemia associated with gout. Hyperuricemia, elevated uric acid levels in the body, is associated with gout, a painful type of arthritis. In clinical trials, febuxostat 40 mg and 80 mg were shown to be effective treatments for the management of hyperuricemia associated with gout. Both doses were well tolerated and required no dose adjustments in patients with renal impairment. The most commonly reported adverse events were upper respiratory tract infections, musculoskeletal and connective tissue signs and symptoms, and diarrhea.
NSAIDs are the current mainstay of treatment for gout flares, despite being associated with an increased risk of gastrointestinal bleeding and cardiovascular events. Janssens et al. conducted a randomized, double-blind, equivalence clinical trial to determine whether the glucocorticoid prednisolone can be used as an alternative to NSAIDs in this setting. Patients referred from primary care community clinics with monosodium urate crystal-proven acute gout flares (n =120) underwent treatment with once-daily oral prednisolone 35 mg or twice-daily oral naproxen 500 mg for 5 days. The results revealed a nonsignificant difference between the two groups, both in the primary outcome measure of pain reduction and in the secondary outcomes of disability related to the affected joint and walking, suggesting equivalence between the two agents. This study helps to position oral glucocorticoids as effective and safe alternatives in the management of acute gout flares. Future studies should address the treatment of acute gout in elderly populations and in those with multiple comorbidities.
Objectives: To examine seasonality and long-term trends in the incidence and prevalence of gout.
Methods: A retrospective study (1994-2007) using routinely collected surveillance data from the Royal College of General Practitioners Weekly Returns Service sentinel general practice network in England and Wales. New cases and acute attacks of gout per 10,000 population were calculated for age groups 0-44, 45-64, 65-74 and 75 years. Long-term trends of annual incidence were assessed by regression analysis. Seasonality indices were calculated using 4-weekly data and the relative risk of gout incidence during the summer was estimated. Annual prevalence was estimated from the consulting patient population (2001-2007) and from prescribing data on defined daily doses (DDDs) of allopurinol (2003-2007).
Results: The annual incidence rate of new gout cases was stable over the period 1998-2007; acute attacks decreased on average 4% per annum. New gout cases and acute attacks combined into 4-weekly incidence rates peaked during the ‘summer’ period of each year. There was an increased risk of gout diagnosis during summer months (late April to mid-September; OR = 1.22 [95% CI 1.18 –C 1.26]). The annual prevalence of gout 2001-2007 was 0.46%, with highest rates recorded in males 75 years (2.57%). Estimated prevalence based on a DDD of 400mg allopurinol was 0.37%.
Conclusion: The incidence of gout is seasonal. This has implications for the management of patients who currently suffer gout, and for those patients who are at risk from future attacks. The decreasing trend in incidence of acute attacks suggests that patient management is improving
Tibialis anterior tendon rupture in gout-Case report and literature review.
Jerome JT, Varghese M, Sankaran B, Thomas S, Thirumagal S. Foot Ankle Surg. 2008;14(3):166-9.
Quote:
BACKGROUND: A case report in which spontaneous rupture of the tibialis anterior tendon occurred secondary to a gouty tophaceous deposit within the tendon. The injury occurs in middle-aged and elderly patients after displacement of the foot in plantar flexion and eversion. The treatment of the rupture is discussed.
METHOD: An appropriate clinical examination, including an exact history taking, leads to the right diagnosis of tibialis anterior tendon rupture in gout. The rupture can occur through abnormal tendons or may occur in any portion of the tendon, but causes little disability if diagnosed promptly.
RESULTS: Repair of the tibialis anterior tendon was done by non-absorbable suture. The leg was immobilized in a plaster cast, and daily active assisted exercises were started at the end of 3 weeks. Patient retained full function, power, and range of motion in foot and ankle at the end of 6 months.
CONCLUSIONS: Closed rupture of the anterior tibial tendon is uncommon in gout, with few cases being reported previously. This report adds to the list of pathological conditions that should be considered in closed spontaneous rupture of the tibialis anterior tendon. Early repair does improve the likelihood of a good result. The problem of the contributory effect of atresia, degenerative changes, or both, has not yet been solved. Primary operative suture, preferably with non-absorbable suture is the treatment of choice for acute ruptures and for patients with high activity levels. Recovery is prompt with little, if any, measurable permanent disability.
Background: Several classification or diagnostic criteria sets for gout have been proposed but none validated.
Objective: This small pilot study considered urate crystal identification as the gold standard for diagnosis and compared the clinical aspects of 3 proposed criteria sets with that standard.
Methods: Eighty-two subjects who had synovial fluid analyses in a VA medical center were studied. ARA (ACR), Rome, and New York clinical criteria sets and individual criteria were recorded in the 30 patients who had urate crystals versus the remainder with no urate crystals.
Results: Presence of 2 of 3 Rome clinical criteria had the highest positive predictive value at 76.9%. None of the 3 studied criteria sets were more than 70% sensitive or 88.5% specific. The clinical features of the ARA (ACR) preliminary classification criteria had 70% sensitivity and 78.8% specificity.
Conclusions: The various proposed clinical criteria can provide support for a diagnosis or exclusion of gout, but unless improved criteria can be developed crystal identification should remain the gold standard.
Arthroscopic elimination of monosodium urate deposition of the first metatarsophalangeal joint reduces the recurrence of gout.
Wang CC, Lien SB, Huang GS, Pan RY, Shen HC, Kuo CL, Shen PH, Lee CH. Arthroscopy. 2009 Feb;25(2):153-8.
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PURPOSE: To determine if the arthroscopic removal of gouty crystal deposits from the first metatarsophalangeal (MTP) joint will reduce the recurrence rate and improve foot function compared to medical treatment alone.
METHODS: Twenty-eight male patients with hyperuricemia (>7.0 mg/dL) and repeated attacks of gouty arthritis of the first MTP joint were included in this study. Arthroscopic intervention of the first MTP joint was performed on 15 patients (group 1), while the other 13 patients were treated with medication alone (group 2). The follow-up period (mean +/- standard deviation) was 3.9 +/- 1.1 years in group 1 and 2.4 +/- 0.3 years in group 2.
RESULTS: After treatment, both groups showed a significant improvement in the number of acute attacks of gouty arthritis and in their functional scores on the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale. On both measures, the results for group 1 were significantly better than those for group 2.
CONCLUSIONS: Arthroscopic removal of gouty crystals from the first MTP joint can reduce the rate of acute repeated attacks of gouty arthritis and increase foot and ankle function.
Objective. According to the written sources several members of the famous Medici family of Renaissance Florence suffered from an arthritic disease, called 'gout' by contemporary physicians; a palaeopathological study allowed verification of the true nature of the 'gout of the Medici' referred by archive document data.
Methods. The skeletal remains of the Grand Dukes and their families, buried in the Basilica of San Lorenzo in Florence, were examined macroscopically and submitted to X-ray investigation.
Results. Out of 15 investigated individuals, two cases of diffuse idiopathic skeletal hyperostosis (DISH), with ossification of the anterior longitudinal ligament and massive hyperostotic changes of the extra-spinal ligaments, were detected in the skeletons of the Grand Dukes Cosimo I (1519-74) and his son Ferdinand I (1549-1609). The left foot of Ferdinand also revealed typical lesions of the uratic gout, confirming the archive data, which describe the disease in detail.
Conclusions. The association between DISH and elite status, highlighted in recent research, receives further confirmation in the present study, furnishing evidence to the significance of this disorder as a lifestyle indicator, linked specifically with a high-caloric diet, consequent obesity and type II diabetes mellitus. Furthermore, the coexistence between DISH and gout observed in Ferdinand represents the first documentation of this association in the palaeopathological literature.
Press Release: ULORIC® (TMX-67, febuxostat) Receives FDA Approval for
the Chronic Management of Hyperuricemia in Patients with Gout
Quote:
Takeda Pharmaceutical Company Limited announced today that on February 13, 2009, Teijin
Pharma’s U.S. licensee for febuxostat and Takeda’s wholly owned subsidiary, Takeda
Pharmaceuticals North America, Inc., (Head office: Deerfield, Illinois) received FDA
marketing approval for ULORIC® (febuxostat) for the chronic management of hyperuricemia
in patients with gout. Takeda Pharmaceuticals North America is the sole developer and
marketer of the product, ULORIC® in the U.S.
Febuxostat was discovered by Teijin Pharma after intensive research, and is an oral,
once-daily, novel highly potent non-purine selective inhibitor of xanthine oxidase(*)
, having a
structure completely different from that of the currently available xanthine oxidase inhibitor,
which was developed over 40 years ago. Febuxostat lowers the level of uric acid in the blood
of hyperuricemic patients with gout, with clinical data supporting its safety and efficacy. In
addition, febuxostat’s safety profile does not require dose adjustment for patients with
mild-to-moderate renal or hepatic impairment.
(*)
An enzyme directly related to the production of uric acid
"This FDA approval granted to Takeda Pharmaceuticals North America, along with the EMEA
(European Medicines Agency) approval given last year to Ipsen, our licensee for febuxostat in
Europe, marks a significant milestone for our global business,” said Osamu Nishikawa, President
of Teijin Pharma. “As to Japan and other areas including Asia, we are proceeding with our plans to
develop febuxostat by ourselves as well as by collaborating with other companies. We will continue
to strengthen our global operations by expanding areas where febuxostat is available and increase
the presence of the product to be widely used by patients worldwide."
“The approval of ULORIC® offers patients and healthcare providers in the U.S., for the first time in
40 years, a novel treatment option for patients who have hyperuricemia with gout, where there are
still unmet clinical needs,” said Yasuchika Hasegawa, President of Takeda. “Together with recently
approved KAPIDEXTM, ULORIC® will significantly enhance Takeda’s product line-up in the U.S. We
expect these products will allow us to further increase our presence in the U.S. Primary Care
Physician (PCP) market”.
First Acute Gout Attacks Commonly Precede Features of the Metabolic Syndrome
Hernández-Cuevas, Claudia Berenice MD*; Roque, Lizandra Hernández MD*; Huerta-Sil, Gabriela MD*; Rojas-Serrano, Jorge MD, MSc*; Escudero, Alejandro MD†; Perez, Letícia Lino MD*; Collantes-Estevez, Eduardo MD†; Mellado, Janitzia Vázquez MD, PhD* Journal of Clinical Rheumatology:Volume 15(2)March 2009pp 65-67
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Objective: To determine in gout patients, the temporal relationship between the first gout attack and the diagnosis of metabolic syndrome (MS), its components and complications.
Subjects and Methods: We included consecutive gout patients attending 2 Rheumatology Departments from Spain (Hospital Universitario Reina Sofía) and México (Hospital General de México). Variables included demographic, clinical, and biochemical data: Hypertension, hypertriglyceridemia, low high density lipoproteins (HDL), obesity, hyperglycemia or diabetes, MS (Adult Treatment Pane III criteria), ischemic heart disease (IHD), and chronic renal failure (CRF). Age and date (year) of the diagnosis of first acute gout attack and associated diseases were obtained.
Results: Four hundred seven patients were included (96% men); mean age at onset, mean age at inclusion, and mean duration of the disease were 39.7 ± 13, 52.5 ± 13, and 13.7 ± 9.9 years, respectively. In 90%, the first attack of gout preceded the diagnosis of features of MS, MS itself or its complications (CRF and IHD), 9.8% had previous diagnosis of at least 1 associated disease.
At the time of the inclusion (mean, 13.7 years after the first attack), 93% had at least 1 associated disease. The most common were hypertriglyceridemia, 63%; obesity, 54%; hypertension, 45.6%; MS, 40%; hyperglycemia, 37%; low HDL, 17%; diabetes, 15%; CRF, 17%; and IHD, 6.6%.
Although patients from the 2 Rheumatology Departments had several demographic and clinical differences, in both groups most of the patients (70% Hospital Universitario Reina Sofía and 95% Hospital General de México) had no diagnosis of any associated disease previous to first bouts and at inclusion most of them had the diagnosis of at least 1 associated disease.
Conclusions: First attacks of gout may precede the diagnosis of metabolic abnormalities and associated diseases, and provids a unique opportunity to diagnose, prevent, and/or retard long-term complications in these patients.
Re: The latest on gout
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