Febuxostat for Treatment of Chronic Gout

Charnelda L. Gray, Pharm.D., BCPS; Nafesa E. Walters-Smith, Pharm.D., BCPS


Am J Health Syst Pharm. 2011;68(5):389-398. 

In This Article


According to the National Health and Nutrition Examination Survey III (NHANES III), an estimated 5.1 million Americans suffer from gout.[6] The self-reported National Health Interview Survey (NHIS) documented the frequency of gout as 0.9%.[6,7] The NHIS found that 2.24% of people age 45–64 years and 3.08% of people age 65 years or older had gout.[7,8] In 2008, Lawrence et al.[9] estimated that 3 million adults age 18 years or older had gout in the previous year and that 6.1 million adults age 20 years or older had an occurrence of gout in their lifetime, though these values are likely overestimates, as self-reported data were not verified.

Hyperuricemia, defined as a serum concentration of uric acid that exceeds the limit of solubility (approximately 7.0 mg/dL), can manifest clinically as the deposition of uric acid crystals in joints and surrounding tissues.[10,11] Individuals with hyperuricemia are usually asymptomatic and do not always have gouty symptoms. In the Normative Aging Study, Campion et al.[12] detailed the risk of gout development relative to serum uric acid levels. The 5-year cumulative risk of gout development in subjects whose serum uric acid concentration was less than 7 mg/dL was 0.6%; for subjects whose serum uric acid concentration was 10 mg/dL or greater, it was 30.5%. Asymptomatic hyperuricemia is not currently managed with pharmacologic agents. Acute gout attacks are attributed to episodes of hyperuricemia in which monosodium urate monohydrate precipitates out of serum and is deposited in joints and tendons, causing local inflammation. Symptoms of acute gout, also known as gouty flare, include sudden onset of pain, fever, limited range of motion, and warmth of the affected area.[5] Hyperuricemia and the presence of monosodium urate monohydrate crystals can occur without an inflammatory response. Persistent or uncontrolled hyperuricemia and repeated acute attacks are categorized as chronic gout. Tophi may appear at any site, typically as firm swellings.[13] Ulcerated tophi may appear as a visible whitish chalky material, while chronic tophaceous gout usually develops after 10 or more years of acute intermittent gout. Progressive joint and bone destruction and renal impairment due to gouty nephropathy and tophaceoous deposits can result if gout is left untreated.[14] Disease progression is not sufficiently prevented by treating acute flare-ups alone.[15]

Diagnosis and Treatment of Gout

Gout is characterized by elevated serum uric acid levels, deposits of monosodium urate monohydrate crystals in the joints and soft tissue, and inflammation. A definitive diagnosis of gout depends on the finding of characteristic crystals. In 1977, the American College of Rheumatology published preliminary criteria for the classification of gout for use in either clinical settings or population-based epidemiologic studies.[13,16] Criteria included monosodium urate monohydrate crystals in synovial fluid during attack, more than one attack of acute arthritis, maximum inflammation developing within one day, mono-arthritis attack, redness observed over joints, pain or swelling in the first metatarsal joint, unilateral first metatarsophalangeal joint attack, unilateral tarsal joint attack, tophus (proven or suspected), hyperuricemia, asymptomatic swelling within a joint on radiograph, subcortical cysts without erosions on radiograph, and joint fluid culture negative for organisms during attacks.[13] Study subjects were classified as having gout if they had monosodium urate monohydrate crystals in synovial fluid, a proven tophus, or at least 6 of the other 11 criteria.

Treatment goals for gout are often aimed at alleviating inflammation and associated pain, stopping the acute flare-up, preventing future flare-ups, preventing deposition of monosodium urate monohydrate crystals, and reducing serum uric acid to target level. Uricosuric agents were used to treat gout near the end of the 19th century and included salicylates, sulfinpyrazone (not widely used due to its unfavorable adverse-effect profile), and benzbromarone.[4,17] Other agents that treat gout include losartan, fenofibrate, amlodipine, sevelamer, and ascorbic acid, though none of these agents are currently approved for treatment of hyperuricemia or gout.[18][21]

Current Therapies

Gout flares typically begin abruptly, with red, hot, or tender joints. Individuals may also be febrile during gouty attacks. Attacks may be polyarticular and can intensify quickly. Colchicine in combination with probenecid or allopurinol is frequently used to treat gouty flares.[22] For acute attacks refractory to or in individuals with contraindications to colchicine and nonsteroidal antiinflammatory drugs (NSAIDs), systemic corticosteroids are typically given.

The current strategy for managing chronic gout is the use of uric-acid-lowering drugs to reduce urate production or of a uricosuric agent to promote renal uric acid excretion. Probenecid is indicated for the management of hyperuricemia associated with chronic gout. By preventing the reabsorption of serum uric acid in the proximal tubule, probenecid corrects underexcretion of uric acid.[23] Xanthine oxidase inhibitors block uric acid production, as xanthine oxidase catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid. Allopurinol has become the most frequently used pharmacologic therapy to lower uric acid and manage chronic gout, demonstrating effectiveness in individuals who overproduce or underexcrete uric acid.

The pharmacologic options to treat gout are fairly limited, and each option has benefits and potential adverse effects. These limited options, coupled with the lack of symptoms outside of those associated with a flare-up, contribute to inconsistent treatment. In addition to adherence challenges, discontinuation of prescription treatment due to adverse effects is also a challenge in the medical management of gout.


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