Date of Graduation

8-15-2009

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Mark Pedemonte, MD

Second Advisor

Rob Rosenow PharmD, OD

Third Advisor

Annjanette Sommers MS, PA-C

Abstract

Background: Gout is a metabolic syndrome characterized by: 1.) hyperuricemia and deposition of urate (uric acid) crystals causing attacks of acute inflammatory arthritis; 2.) tophi around the joints and possible joint destruction; 3.) renal glomerular, tubular and interstitial disease and; 4.) uric acid urolithiasis. According to the U.S. Census Bureau, whose numbers were obtained from a year 2005 population estimate study, gout affected an estimated 6.1 million adults aged 20 years old and older. Many challenges are faced with the treatment of gout, however, the mainstay of hypouricemic treatment has been the conventional use of allopurinol. In February of 2009, the FDA approved a new medication, Uloric (febuxostat), which claimed to be more effective than Zylporim (allopurinol) for chronic sufferers of gout who have long been dissatisfied with previously available options in the treatment of hyperuricemia.

Hypothesis: Patients who did not receive the expected level of benefit from treatment with allopurinol to adequately reduce urate levels in the body, now have a greater likelihood of success with the aid of a new pharmaceutical tool, febuxostat.

Study Design: A review of literature on Uloric (febuxostat), as well as Zyloprim (allopurinol), was performed via an exhaustive search of available studies within the time frame ranging from 2004 through the present, completed on the adult population, utilizing Medline-Ovid, Web of Science, WorldCat.org, PubMed, and the Chochrane Central Register of Randomised Controlled Trials.

Methods: Including a search of the keywords listed below, multiple reference lists of articles obtained were also checked for any additional sources that might have been overlooked in the original search. Studies that were included were phase I through phase III clinical trials that examined solely febuxostat, as well as febuxostat compared to allopurinol. Studies that were excluded were those that did not primarily focus on the treatment of gout utilizing the two aforementioned medications—e.g. probenecid, indomethacin, and colchicine. As a result, a systematic review of the obtained literature regarding the comparison of febuxostat-treatment versus allopurinol-treatment on hyperuricemia and gout was completed.

Results: A combination of phase I and phase II trials, eight in total, were analyzed for background testing completed on the new drug. Two critical Phase III Randomly-Controlled Trial articles with two additional long term studies were obtained that displayed febuxostat to have an advantage over allopurinol in the treatment of hyperuricemia and gout.

Conclusion: Febuxostat proved to be more effective in reducing the serum uric acid concentration in subjects with hyperuricemia and gout. Febuxostat showed promising hypouricemic effects among those individuals tested with renal-impairment, distancing itself from allopurinol. However, due to the recentness of FDA approval and unfamiliarity in the clinic setting, further observations of febuxostat’s long term efficacy and safety need to be done on a greater number of gout and hyperuricemic patients.

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