According to a study in the August 17 issue of JAMA, patients with severe, chronic gout who took pegloticase for 6 months as an alternative to conventional gout treatment that some patients may not respond to, showed greater improvements of uric acid levels as well as physical function and quality of life.
According to background information in the article, a lowering treatment for long-term urate (a salt derived from uric acid) aims to maintain concentrations of uric acid (UA) below a certain level; however, it is normal for UA levels to raise above a recommended goal urate scale during oral urate-lowering therapy among 5 to 6 million gout sufferers in the United States.
Even though oral urate-lowering medications available can achieve a target UA in most patients, it proves ineffective in approximately 3 percent of patients because of refractoriness (resistant to treatment), contraindication, or intolerance.
When the urate is not lowered effectively, many of these patients may develop severe chronic gout, characterized by symptoms, such as frequent arthritic flares and chronic arthropathy (joint disease), which is often accompanied by deformity, chronic, pain, functional disability, and impaired health-related quality of life (QOL).
The recently approved drug pegloticase, developed for use where conventional urate-lowering drugs are ineffective, is administered intravenously and remains in the circulation where it degrades urate.
John S. Sundy, M.D., Ph.D., of Duke University Medical Center, Durham, N.C., and his colleagues report findings of two randomized, placebo-controlled, 6-month trials of pegloticase in patients with refractory gout in terms of their ability to lower urate, clinical efficacy and tolerability.
The trials (C0405 and C0406) were conducted at 56 rheumatology practices in the United States, Canada, and Mexico between June 2006 and October 2007 comprising of participants suffering from severe gout, allopurinol (a drug to treat gout) intolerance or refractoriness, with a serum uric acid concentration of 8.0 mg/dL or greater.
Of 225 participating patients, 109 took part in trial C0405 and 116 participated 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 outcome measure was plasma uric acid levels of less than 6.0 mg/dL measured at months 3 and 6.
Researchers discovered when they analyzed separately by dose, that patients treated with biweekly pegloticase achieved response rates of 47 percent (20/43) and 38 percent (16/42) of meeting the primary outcome in the 2 trials. Those treated with monthly pegloticase showed response rates of 20 percent (8/41) and 49 percent (21/43), with 0 percent response rate in both placebo groups.
The authors write, "When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42 percent), 29 of 84 patients in the monthly group (35 percent), and 0 of 43 patients in the placebo group".
The average plasma UA for those who responded in the trial was significantly below 6.0 mg/dL for the entire 6-month treatment period.
Researchers also discovered, that both pegloticase dosing groups reported significant improvements in physical function and QOL compared with the placebo group.
Patients participating in the biweekly pegloticase group reported a significant reduction in pain compared to the placebo group.
Over 90 percent of participants in each treatment group experienced one or more adverse events (AE) with serious AEs occurring more frequently in patients treated with biweekly (24 percent) and monthly pegloticase (23 percent) than in patients receiving placebo (12 percent).
The most common AE was Gout flare, which was reported in approximately 80 percent of patients across the 3 pooled study groups. Seven patients died (4 among patients assigned pegloticase and 3 in the placebo group) between randomization and closure of the study database (February 15, 2008).
The authors comment, "These parallel, 6-month, placebo-controlled trials of pegloticase treatment have documented sustained UA 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".
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