Gout – pegloticase
Drugs such as allopurinol and probenecid can be used to reduce uric acid levels, but do not work in all patients
Gout occurs when too much uric acid accumulates in the synovial fluid and crystallises out in the joint. If the disease becomes chronic, lumps under the skin around the joints (tophi) may develop.
Drugs such as the xanthine oxidase inhibitor allopurinol and the uricosuric agent probenecid can be used to reduce uric acid levels, but do not work in all patients. Savient Pharmaceuticals has developed pegloticase, a PEGylated recombinant mammalian uricase that converts uric acid to allantoin, which is significantly more soluble. The PEGylation increases its half-life from a few hours to 10 to 12 days.
In a 12–14 week Phase II trial, 41 patients who had failed previous gout treatments were given 4 or 8mg pegloticase every two weeks, 8mg every two or four weeks, or 12mg every four weeks.1 While 88% of all patients experienced gout flares, the mean plasma urate level fell to 6mg/dl or lower after six hours, and was sustained throughout the trial period for those given 8 or 12mg doses. The most effective dosage was established as 8mg every two weeks. Most adverse events were mild or moderate, and not related to treatment.
In another pair of randomised, double blind trials, this time placebo-controlled, a total of 225 patients were given biweekly infusions of 8mg pegloticase, 8mg alternating with placebo, or placebo for six months.2 Overall, the primary endpoint of plasma uric levels falling and remaining below 6mg/dl was achieved in 36 of the 85 patients given biweekly injections, 29 of the 84 monthly dose patients, and none of the 43 patients given placebo.
In an open-label safety extension study, patients were given 8mg doses of pegloticase either biweekly or monthly.3 Gout flares and infusion-related adverse events were the most common, with a lower incidence in those patients who had a sustained urate response and those given biweekly doses.
References
1. J.S. Sundy et al. Arth. Rheum. 2008, 58, 2882
2. J.S. Sundy et al. JAMA 2011, 306, 711
3. M.A. Becker et al. Ann. Rheum. Dis. 2012, Nov 10 (epub ahead of print) doi:10.1136/annrheumdis-2012-201795