Individuals with severe, chronic gout who have not responded to conventional treatment may benefit from six-months’ worth of pegloticase treatment. Researchers from Duke University Medical Center, Durham, N.C., reported in JAMA (Journal of the American Medical Association) that individuals experienced better levels of uric acid as well as physical function, quality of life, and less pain.
The aim of long-term urate reduction therapy among individuals with gout is to keep uric acid concentrations below a certain level. However, uric acid levels commonly exceed the recommended range during this therapy in a significant number of patients, the authors explained.
Oral urate-lowering medications generally work for most patients with gout. Unfortunately, for about 3% of them this is not possible, either because they are resistant to treatment, intolerant of the medication, or cannot take it (contraindication).
If urate levels among these patients is not effectively lowered, their condition can progress to severe chronic gout, and may include:
- Chronic arthropathy
- Chronic pain
- Frequent arthritic flares
- Functional disability
- Poor quality of life
Pegloticase was created for individuals who did not respond to conventional urate-lowering agents. It is administered intravenously and stays in circulation where it breaks down urate.
John S. Sundy, M.D., Ph.D., and team write about the results of two placebo-controlled, randomized, 6-month human trials of pegloticase in patients with refractory gout. The trials examined the clinical efficacy and tolerability of the urate-lowering drug.
The two trials, known as C0405 and C0406, involved 225 patients and were performed between June 2006 and October 2007 at 56 different rheumatology practices in the USA, Mexico and Canada. All patients had severe gout, were intolerant to allopurinol, and had serum uric acid concentrations of at least 8.0 mg/dL. Allopurinol is a standard drug for the treatment of gout.
Trial C0405 included 109 patients while C0406 had 116 patients. They were randomly selected into one of three groups:
- Biweekly treatment group – 12 biweekly injections containing pegloticase 8 mg at each infusion
- Monthly treatment group – pegloticase alternating with placebo at successive infusions
- Placebo group – they received a placebo
Their uric acid levels were measured at 3 and 6 months. The primary endpoint was plasma uric acid levels of less than 6.0 mg/dL.
The researchers found that:
- 47% and 38% of those in the biweekly treatment groups met the two trials’ primary outcome
- 20% and 49% of those in the monthly treatment group met the two trials’ primary outcome
- The response rate among the placebo groups in both trials was 0%
- Among those who responded, their plasma uric acid levels were considerably below 6.0 mg/dL for the whole of the six month period
Those receiving pegloticase experienced considerable improvements in physical function and quality of life compared to those on placebo. Patients in the biweekly treatment groups also reported significantly reduced pain compared to those in the placebo groups.
90% of patients in each treatment group experienced at least one adverse event. 24% of those in the biweekly treatment groups experienced a severe adverse event, compared to 23% in the monthly groups and 12% in the placebo groups. 80 patients reported gout flare, the most common adverse event. 4 patients receiving pegloticase and 3 in the placebo groups died between randomization and closure of the study database (Feb 15, 2008).
The authors wrote:
“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.”
Written by Christian Nordqvist