SAN FRANCISCO — The investigational drug pegloticase significantly reduced serum urate levels compared with placebo in two randomized, double-blind studies of 212 patients with gout who had previously failed treatment with allopurinol.
Patients received intravenous infusions of placebo or 8 mg pegloticase (Puricase) every 2 or 4 weeks in the 24-week Gout Outcome and Urate Therapy studies (GOUT1 and GOUT2), the results of which were presented by Dr. John S. Sundy at the annual meeting of the American College of Rheumatology.
At baseline, all patients had a serum urate level that was higher than 8 mg/dL (an average of 10 mg/dL) and severe, symptomatic gout, with three or more gout flares in the previous 18 months (an average of 10 flares), one or more tophi (present in 73% of patients), or chronic gouty arthropathy (present in 58% of patients in the studies).
The patient cohort had had gout for a mean of 15 years.
Allopurinol treatment was contraindicated or had failed to reduce serum urate to below 6 mg/dL in these patients.
Treatment in the study was considered successful if a patient's uric acid readings were within the normal range (less than 6 mg/dL) at least 80% of the time in months 3 and 6 of the studies.
None of the patients in the placebo groups of either the 104-patient GOUT1 study or the 108-patient GOUT2 study achieved this goal in the intent-to-treat analysis, according to Dr. Sundy.
However, on a regimen of pegloticase every 2 weeks, 47% of the patients in GOUT1 and 38% of patients in GOUT2 were treated successfully.
On a treatment regimen of pegloticase every 4 weeks, 20% of GOUT1 patients and 48% of GOUT2 patients achieved successful improvements, reported Dr. Sundy, who is a rheumatologist at Duke University, Durham, N.C., and his associates.
The serum urate improvements that were seen with both of the pegloticase regimens were significant compared with placebo, he commented.
Dr. Sundy disclosed that the company that makes pegloticase, Savient Pharmaceuticals, both funded the study and has given research funds or other payments to Dr. Sundy and many of the other investigators on this study, some of whom are Savient employees.
Additionally, Duke University and one of its employees who was not involved in the study hold patents on pegloticase.
A total of eight serious cardiovascular events occurred in patients getting pegloticase: two cardiac arrests, two exacerbations of heart failure leading to death in one patient, two dysrhythmias, one myocardial infection, and one case of angina.
Among other side effects, infusion reactions led to discontinuation of treatment in 11%–13% of patients on pegloticase and none on placebo.
Dr. Sundy said the cardiovascular events “may reflect underlying comorbidity.”
A physician in the audience challenged this assumption, saying the events should occur in the placebo group, too, if that were the case.
A current, ongoing 12-month open-label extension of the study might soon shed some light on this, Dr. Sundy said.
Secondary measures of efficacy in the double-blinded studies found clinically and statistically significant improvements in the pegloticase groups compared with placebo.
Among patients with at least one tophus who were evaluated by computer-assisted photographic analysis, a tophus resolved completely in 21 (40%) of 52 patients getting pegloticase every 2 weeks and 11 (21%) of 52 patients getting pegloticase every 4 weeks, compared with 1 (4%) of 27 patients on placebo.
The number of tender joints decreased by seven in the 2-week pegloticase group and by six in the 4-week group compared with an average decrease of one tender joint on placebo. The number of swollen joints did not differ significantly between groups.
Both pegloticase groups, but not the placebo group, showed significant improvements in the Short Form-36 Health Survey physical component summary score and the physical functioning subscale of the Health Assessment Questionnaire-Disability Index.
The study cohort was 82% male, with a mean age of 55 years and a high degree of comorbidity.
Hypertension was present in 72% of patients, chronic kidney disease in 30%, diabetes in 22%, hypercholesterolemia in 21%, and coronary artery disease in 11% of the patients.
Pegloticase is a recombinant mammalian urate oxidase modified with polyethylene glycol that converts urate to allantoin.