As an alternative to a conventional treatment for gout that some patients may not respond to, patients with severe, chronic gout who received the medication Pegloticase ( Krystexxa ) for 6 months had greater improvement in measures of uric acid levels as well as physical function and quality of life.

Long-term urate lowering therapy in gout aims to maintain concentrations of uric acid below a certain level. However, it is common for uric acid levels to exceed a recommended goal urate range during oral urate-lowering therapy among the 5 to 6 million U.S. patients with gout.
Although available oral urate-lowering agents can achieve target uric acid in most patients, urate-lowering therapy fails for perhaps 3 percent of patients because of refractoriness, contraindication, or intolerance. Without effective urate lowering, many such patients may progress to severe chronic gout characterized by symptoms including frequent arthritic flares and chronic arthropathy, often accompanied by deformity, chronic pain, functional disability, and impaired health-related quality of life ( QOL ).
Pegloticase, a recently approved drug, was developed for patients in whom conventional urate-lowering agents are not effective. The drug is intravenously administered and remains in the circulation where it degrades urate.

John S. Sundy, of Duke University Medical Center, Durham, and colleagues have reported results of two randomized, placebo-controlled, 6-month trials of the urate-lowering and clinical efficacy and tolerability of Pegloticase in patients with refractory gout. The trials ( C0405 and C0406 ) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, Allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater.
A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. Patients received 12 biweekly intravenous infusions containing either Pegloticase 8 mg at each infusion ( biweekly treatment group ), Pegloticase alternating with placebo at successive infusions ( monthly treatment group ), or placebo.
The primary measured outcome was plasma uric acid levels of less than 6.0 mg/dL measured at months 3 and 6.

The researchers found that when analyzed separately by dose, patients treated with biweekly Pegloticase experienced response rates of 47% and 38% in the 2 trials. Patients treated with monthly Pegloticase reported response rates of 20% and 49%, and response rates were 0% in both placebo groups.
When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group ( 42% ), 29 of 84 patients in the monthly group ( 35% ), and 0 of 43 patients in the placebo group.
Average plasma uric acid for responders was substantially below 6 mg/dL for the entire 6-month treatment period.

The researchers also found that both Pegloticase dosing groups reported significant improvements in physical function and QOL compared with placebo. Patient-reported pain was significantly reduced with biweekly Pegloticase versus placebo.

One or more adverse events occurred in more than 90% of participants in each treatment group. Serious adverse events occurred more frequently in patients treated with biweekly ( 24% ) and monthly Pegloticase ( 23% ) than in patients receiving placebo ( 12% ).
Gout flare was the most common adverse event and was reported in approximately 80% of patients across the 3 pooled study groups.
Seven deaths ( 4 among patients assigned Pegloticase and 3 in the placebo group ) occurred between randomization and closure of the study database ( February 15, 2008 ).

In conclusion, these parallel, 6-month, placebo-controlled trials of Pegloticase treatment have documented sustained uric acid reductions and significant clinical improvements in a substantial proportion of patients with chronic gout and refractoriness to, or intolerance of, conventional urate-lowering therapy. The significant disease-modifying benefits of Pegloticase given every 2 weeks were demonstrable within 6 months, a time frame unique in randomized controlled trials of urate-lowering agents.

Source: JAMA, 2011

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