Patients who have not had successful treatment for their gout may find new hope in pegloticase, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

Gout is a painful and potentially disabling form of arthritis that has been recognized since ancient times. Initial symptoms usually consist of intense episodes of painful swelling in single joints, most often in the feet (especially the big toe). Treatments are available to control most cases of gout, but diagnosing this disorder can be difficult and treatment plans often have to be tailored for each person.

Researchers recently studied 212 patients with gout who were either treated intravenously with pegloticase (Puricase®) or placebo in duplicate six-month, double-blind, randomized studies. Researchers recently studied 212 patients with gout who were either treated intravenously with pegloticase (Puricase®) or placebo in duplicate six-month, double-blind, randomized studies. Participants were eligible to participate if they had been unsuccessfully treated – experiencing three or more gout arthritis flares in the previous 18 months, had one or more joints affected by chronic gout, or had tophi; a serum urate level greater than 8mg/dL; and either intolerance of allopurinol or no success taking the highest medically appropriate dose of allopurinol.

Participants in both studies were divided into three groups, and received 8mg of pegloticase every two weeks, 8mg of pegloticase every four weeks, or placebo. Researchers considered the treatment successful for a participant if he or she had uric acid readings within the normal range at least 80 percent of the time in months three and six of the studies. In addition to reviewing plasma uric acid levels, researchers looked at the size of tophi, which are chalky deposits of uric acid often found in gout patients, the incidence of gout flares, the tenderness and swelling of joints, quality of life, safety and disability.

Participants—mostly men with an average age of 55 years and many who had additional medical conditions including high blood pressure, chronic kidney disease, heart disease and diabetes—were found to have a significantly better response to pegloticase over placebo in both studies. The number of gout flares did not significantly differ between the two groups; however, complete resolution of tophi was noted in more patients taking pegloticase over placebo. These patients noticed improved physical function as well. Serious adverse reactions were more common with pegloticase than with placebo.

Overall, pegloticase was successful in treating 40 percent of the participants, with significant improvement in clinical outcomes.

“Patients with treatment failure gout suffer from severe pain, increased disability and reduced quality of life, explains John S. Sundy, MD, PhD; associate professor of medicine; Duke University Medical Center, Durham, N.C., and lead investigator in the study “Therefore, these findings are exciting because they show that pegloticase was able to reduce urate levels and improve clinical outcomes in subjects with gout who had exhausted all available treatment options.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.

Editor’s Notes: Dr. Sundy will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 11:15 – 11:30 AM on Sunday, October 26, in the Moscone Center. Dr. Sundy will be available for media questions and briefing at 1:30 PM on Sunday, October 26 in the on-site press conference room, 114.

Presentation Number: 635

Efficacy and Safety of Intravenous (IV) Pegloticase (PGL) in Subjects with Treatment Failure Gout (TFG): Phase 3 Results from GOUT1 and GOUT2

J. S. Sundy1, H. S. Baraf2, M. A. Becker3, N. L. Edwards4, S. R. Gutierrez-Urena5, E. L. Treadwell6, J. Vázquez-Mellado7, R. A. Yood8, Z. Horowitz9, B. Huang9, A. Maroli9, R. Waltrip9. 1Duke University Medical Center, Durham, NC; 2Center for Rheumatology & Bone Research, Wheaton, MD; 3University of Chicago, Chicago, IL; 4University of Florida, Gainesville, FL; 5Hospital Civil de Guadalajara, Guadalajara, Mexico; 6East Carolina University, Greenville, NC; 7Hospital General de México, Mexico City, Mexico; 8Fallon Clinic, Worcester, MA; 9Savient Pharmaceuticals, Inc., East Brunswick, NJ

Purpose: To assess the efficacy and safety of PGL (PEGylated recombinant mammalian uricase) in the management of TFG.

Methods: TFG subjects (212) were treated with IV PGL or placebo (PBO) in replicate 6 month randomized, double blind, studies, Gout Outcome and Urate Therapy (GOUT1 and GOUT2). Subjects were randomized to PGL 8 mg q2w (n=85), 8 mg q4w (n=84), or PBO (n=43). TFG was defined as: ≥3 flares in the previous 18 months, or ≥1 tophus, or gouty arthropathy; serum urate >8.0 mg/dL; and prior failure of maximum medically appropriate dose of allopurinol or contraindication to allopurinol. Subjects with plasma uric acid (PUA)

<6.0 mg/dL 80% of the time in months 3 and 6 met the primary endpoint in the ITT analysis. Data were pooled for secondary endpoints: reduction of tophus size, gout flare incidence, swollen joints (SJ), tender joints (TJ), quality of life by SF-36, disability by HAQ-DI, and safety.

Results: Subjects at baseline were: 82% male; mean age 55 yrs; and with a high degree of comorbidity: hypertension (71%), chronic kidney disease (43%), cardiovascular disease (31%), and diabetes (22%). Both PGL groups were significantly superior to PBO for the primary efficacy endpoint in both studies.

Complete resolution of ≥1 tophus occurred in 21/52 q2w, 11/52 q4w, and 2/29 PBO subjects (P=0.002 q2w vs PBO). SF-36 physical component summary score and HAQ-DI for physical functioning improved significantly in both PGL groups. Subjects on PGL had significantly greater reductions in TJs, but not SJs, vs PBO [q2w: -7.4±12.0 (P=0.008), q4w: -6.1±10.6 (P=0.024), PBO: -1.2±12.3). Gout flares and infusion reactions (IRs) were the most common adverse events (AEs). The number of gout flares in the PGL groups did not differ significantly from PBO. IRs occurred in 26% q2w, 40% q4w, and 5% PBO subjects and were the most common reason for study withdrawal. Serious AEs occurred in 24% q2w, 23% q4w, and 12% PBO subjects.

Conclusion: In subjects who have failed available treatment, PGL achieved the primary endpoint for reduction in PUA in ~ 40% of subjects. Improvement in clinical outcomes was observed in a significant proportion of subjects. The most frequent AEs were gout flares and IRs.

Disclosure Block: J.S. Sundy, Savient Pharmaceuticals, Inc, 2; H.S. Baraf, Savient Pharmaceuticals, Inc., 2; Savient Pharmaceuticals, Inc, 5; M.A. Becker, Savient Pharmaceuticals, Inc., 5; N.L. Edwards, Savient Pharmaceuticals, Inc., 2; Savient Pharmaceuticals, Inc., 5; S.R. Gutierrez-Urena, Savient Pharmaceuticals, Inc., 2; E.L. Treadwell, Savient Pharmaceuticals, Inc., 2; J. Vázquez-Mellado, Savient Pharmaceuticals Inc., 2; R.A. Yood, Savient Pharmaceuticals, Inc., 2; Z. Horowitz, Savient Pharmaceuticals, Inc., 1; Savient Pharmaceuticals, Inc, 3; B. Huang, Savient Pharmaceuticals, Inc., 3; Savient Pharmaceuticals, Inc., 1; A. Maroli, Savient Pharmaceuticals, Inc., 1; Savient Pharmaceuticals, Inc., 3; R. Waltrip, Savient Pharmaceuticals, Inc., 1; Savient Pharmaceuticals, Inc., 3.

Source: American College of Rheumatology (ACR)