Uloric (Febuxostat) is the first prescription drug to be approved by the FDA for lowering uric acid levels in over 40 years. Patients who are still having gout attacks and continue to have high uric acid levels despite treatment now have another treatment option.
The prevalence of gout is increasing, attributed mainly to increases in both longevity, and obesity. Gout is characterized by severe pain and swelling in the affected joint, and reduced joint mobility. Gout flares can last anywhere from a few hours to weeks at a time. Chronic gout can lead to permanent joint damage and disability. For more background information follow the links below to our previous articles on gout:
– IL-1 Inhibitors – A New Drug Class for Treating Gout: http://www.clinicaltrialsmagazine.com/il-1-inhibitors-new-drug-class-treating-gout/
– International Standards for the Treatment of Gout: http://www.clinicaltrialsmagazine.com/international-standards-treatment-gout/
– Gout: The Do’s and Do Not’s of Lifestyle Change: http://www.clinicaltrialsmagazine.com/gout-the-dos-and-do-nots-of-lifestyle-change/
Gout treatment guidelines recommend treating gout symptoms with non-steroidal anti-inflammatory drugs, corticosteroids, or oral colchicine. For long-term management of the condition, keeping a uric acid levels of less than 360mmol/L is the goal. Allopurinol is the current mainstay drug for maintenance of uric acid levels in patients with gout. Allopurinol works by interfering with the biosynthesis of purine, via inhibition of xanthine oxidase. Xanthine oxidase is an enzyme necessary for the oxidation process of hypoxanthine and xanthine into uric acid. By blocking this oxidation process, allopurinol inhibits production of uric acid. For patients who are unresponsive to allopurinol treatment, or become intolerant, there have been few options available until now.
A new option for gout treatment is Uloric (Febuxostat), which was approved by the FDA in 2009. Uloric functions as a selective inhibitor of the xanthine oxidase enzyme. It selectively blocks the active site on the enzyme, thereby specifically preventing the oxidization of hypoxanthine and xanthine into uric acid. While clinical trials have demonstrated the safety of Uloric using doses of up to 240mg, the FDA has only approved it for use at doses of 40mg and 80mg per day. Studies have demonstrated that when given 40mg of Uloric daily, the amount of patients reaching target uric acid levels matched those of patients taking allopurinol. However, when taking 80mg/day of Uloric, up to twice as many patients reached target uric acid levels when compared to those taking allopurinol, suggesting that this new medication has the potential to surpass its predecessor in usage and effectiveness. Importantly, Uloric can be taken by patients with mild to moderate kidney problems, without adjusting the dose, unlike allopurinol. In addition, clinical studies have shown similar pharmacokinetics in the geriatric population, and therefore no dose adjustment is required with age. Common side effects found with Uloric treatment include: nausea, diarrhea, arthralgia, headache, elevated liver function tests, and rash. The American College of Rheumatology’s Gout Guidelines now recommend the use of either allopurinol or Uloric as first line drugs in the treatment of gout.
Uloric is currently in clinical trials in over 470 locations across the US, Canada, and Mexico. There are two studies which are assessing both the safety and effectiveness of extended release Uloric compared with immediate release Uloric in patients with gout, and in patients with moderate renal impairment. These studies will determine if extended release Uloric is an effective treatment for lowering uric acid levels and reducing the frequency of gout flares. These two studies are enrolling participants who:
– Are 18 years of age or older, who have been diagnosed with gout
– Have increased serum uric acid levels
– Have had at least one gout flare within 12 months prior to screening visit
– Have an estimated glomerular filtration rate of ≥30 mL/min and
A third study being conducted is a long-term study that will test whether patients with gout, who receive Uloric for up to 9 years, will have an increased risk of cardiovascular events, including: heart attack, stroke, and angina. This study will be enrolling approximately 7500 patients, which will include: males who are 50 years of age or older, or females 55 years of age or older (at least 2-years post-menopausal), with gout and health problems affecting the heart or blood vessels. The study will be conducted in approximately 450 study centers in North America.
Due to the fact that gout patients often have co-existing health conditions, such as kidney failure, or cardiovascular disease, these studies are important to determine the safety and efficacy of Uloric in this challenging subset of patients.
Edwards, NL, So, A. “Emerging Therapies for Gout” Rheumatic Disease Clinics of North America, (40):2, p375-387, May 2014.
Richette, P, Frazier, A, Bardin, T. “Pharmacokinetics considerations for gout treatments” Expert Opinion on Drug Metabolism & Toxicology, 10(7), p949-957, July 2014.
Khanna, PP, Gladue, HS, Singh, MK, FitzGerald, JD, Bae, S, Prakash, S, Kaldas, M, Gogia, M, Berrocal, V, Townsend, W, Terkeltaub, R, Khanna, D. “Treatment of acute gout: A systematic review” Seminars in Arthritis & Rheumatism, Published Online: February 12, 2014. DOI: http://dx.doi.org/10.1016/j.semarthrit.2014.02.003
Uloric Information Sheet. Available from: www.uloric.com Last Accessed: June 18, 2014.
Grewal, HK, Martinez, JR, Espinoza, LR. “Febuxostat: drug review and update” Expert Opinion on Drug Metabolism & Toxicology, 10(5), p747-758, May 2014.
Clinicaltrials.gov “Cardiovascular Safety of Febuxostat and Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES)” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01101035?term=01101035&rank=1 Last Accessed: June 18, 2014.
Clinicaltrials.gov “Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout and Moderate Renal Impairment” Available from: http://www.clinicaltrials.gov/ct2/show/NCT02128490?term=02128490&rank=1 Last Accessed: June 18, 2014.
Clinicaltrials.gov “Efficacy and Safety of Extended Release and Immediate Release Febuxostat in Participants With Gout” Available from: http://www.clinicaltrials.gov/ct2/show/NCT02139046?term=02139046&rank=1 Last Accessed: June 18, 2014.
Image courtesy of ddpavumba / FreeDigitalPhotos.net
Written by Deborah Tallarigo, PhD