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1.  New advances in the treatment of gout: review of pegloticase 
Treatment-failure gout (TFG) affects approximately 50,000 patients or about 1% of the overall population of patients with gout in the United States of America. The severity of TFG is manifested by frequent acute attacks of disabling arthritis, chronic deforming joint disease, destructive masses of urate crystals (tophi), progressive physical disability, and poor health-related quality of life. Pegloticase (Krystexxa®; Savient Pharmaceuticals, Inc), a novel PEGylated urate oxidase (uricase) enzyme, has been resubmitted for US Food and Drug Administration approval. In a 6-month, placebo-controlled clinical trial, 8 mg of pegloticase for every 2 weeks induced a lytic decrease of serum urate (sUr) concentrations, leading to dissolution of tophi in 40% of patients at final visit. However, 58% were nonresponders to the defined target sUr of 0.36 mmol/L (80% were nonresponders during months 3 and 6), possibly due to anti-body formation. Also, 26%–31% experienced infusion reactions (IRs) and 77% suffered from gout flares. Although long-term data are awaited, an anti-inflammatory strategy, eg, based on glucocorticosteroids, is needed to prevent pegloticase antibody formation leading to IRs and diminished or shortened efficacy, and might also prevent gout flares. According to the current clinical data, pegloticase might have an important role as a (bridging) treatment in sUr-responsive patients for tophi clearance in severe chronic refractory gout.
doi:10.2147/TCRM.S6043
PMCID: PMC2988614  PMID: 21127695
pegloticase; hyperuricemia; gout; pharmacotherapy; PEG-uricase
2.  Management of hyperuricemia in gout: focus on febuxostat 
Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than “standard dosage” allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol.
PMCID: PMC2817937  PMID: 20169038
aging; febuxostat; hyperuricemia; gout; pharmacotherapy; xanthine oxidase

Results 1-2 (2)