COPENHAGEN — Patients with refractory chronic gout who were put on pegloticase had statistically significant and clinically meaningful improvements in their health-related quality of life after 25 weeks of treatment in two placebo-controlled studies with a total of 157 patients.
Refractory chronic gout accounts for a small subset of patients with gout (about 1%-2%) who have significantly lower health-related quality of life scores than do age- and sex-matched norms. Combined results from two similar studies of the investigational drug pegloticase showed that, in addition to significantly cutting disease activity and pain, the pegloticase regimen improved other physical and mental domains and resulted in normal or near-normal values in more than half the domains measured on the SF-36 (Medical Outcomes Study 36-Item Short Form Health Survey), Dr. Vibeke Strand said at the annual European Congress of Rheumatology. About 50,000 Americans have treatment-resistant gout, she estimated.
“We never before had gout patients report feeling better by function, global assessment, pain, and health-related quality of life, so it's a very clinically meaningful result,” Dr. Strand said in an interview. “Treatment-failure gout affects not just the physical domains, but the mental domains, too.”
Savient Pharmaceuticals Inc. announced on Aug. 2 that the Food and Drug Administration had notified the company that its intravenous drug pegloticase, under review for treating chronic gout in refractory patients, could not be approved at this time, partly because of manufacturing issues. The company plans to meet with the agency to address these issues, according to the statement.
Without pegloticase treatment, patients with refractory chronic gout have an average health-related quality of life (QOL) that's worse than that of patients with osteoarthritis and hypertension, and worse than that of patients with angina and hypertension, said Dr. Strand, a rheumatologist at Stanford (Calif.) University. The severity of their health-related quality of life is comparable to that of patients with long-standing rheumatoid arthritis and patients with active systemic lupus erythematosus, she added.
Dr. Strand and her associates measured improvements in quality of life in 157 of the 212 total patients enrolled in two similar trials, the GOUT (Gout Outcomes and Uric Acid Treatment) 1 and GOUT 2 studies. Both studies randomized patients with treatment-resistant gout to treatment with 8 mg pegloticase administered by a 2-hour IV infusion every 2 weeks, 8 mg pegloticase infused once every 4 weeks, or placebo. Treatment continued for 25 weeks.
Pegloticase is a pegylated form of a modified, mammalian urate oxidase. The study was funded by Savient Pharmaceuticals, which is developing pegloticase (Krystexxa). Dr. Strand reported receiving research support from and serving as a consultant to Savient.
The primary outcome of the pivotal GOUT 1 and GOUT 2 studies was the proportion of patients with normalization of their plasma uric acid level during the final 3 months on treatment. Data in prior reports showed that this was significantly boosted by pegloticase treatment in these two studies.
The new analysis examined data collected at baseline and after 25 weeks on treatment from the SF-36 (with eight domains) and the HAQ-DI (Health Assessment Questionnaire–Disability Index). Baseline levels showed SF-36 domain scores that were 15-30 points (on a 0-100 scale) below U.S. normative levels. The HAQ-DI scores reflected moderate to severe levels of disability, Dr. N. Lawrence Edwards, Dr. Strand, and their associates reported in a poster presented at the congress.
For example, scores in the physical function domain averaged 45 in the 212 patients with refractory chronic gout, compared with 60 in age- and sex-matched norms. Average mental health domain scores were 68 in patients vs. 79 in age- and sex-matched norms.
The average domain scores in the gout patients who were enrolled in the two pegloticase studies were similar to the average SF-36 domain scores in a longitudinal study of 110 patients with refractory chronic gout, and in a third study of about 1,500 Veterans Affairs patients with gout, according to a second report at the meeting by Dr. Strand.
The 85 patients in GOUT 1 and GOUT 2 who received pegloticase every 2 weeks had “clinically-meaningful” improvements in their average SF-36 scores for all eight domains, reported Dr. Edwards, professor of rheumatology at the University of Florida in Gainesville, and his associates in their poster. Improvements, compared with baseline, were greatest for bodily pain, physical functioning, physical role, and social functioning. Pegloticase every 2 weeks for 25 weeks led to normal or near-normal average scores for five domains: bodily pain, mental health, emotional role, social functioning, and vitality. Pegloticase also produced significant improvements in HAQ-disability index scores.