Long-term safety of pegloticase in chronic gout refractory to conventional treatment
- Michael A Becker1,
- Herbert S B Baraf2,
- Robert A Yood3,
- Aileen Dillon4,
- Janitzia Vázquez-Mellado5,
- Faith D Ottery6,
- Dinesh Khanna7,
- John S Sundy8
- 1Rheumatology Section, The University of Chicago, Chicago, Illinois, USA
- 2Center for Rheumatology and Bone Research, Wheaton, Maryland, USA
- 3Reliant Medical Group, Worcester, Massachusetts, USA
- 4Rheumatology Section, Kaiser Permanente Medical Center, San Francisco, California, USA
- 5Department of Rheumatology, Hospital General de Mexico, Mexico City, Mexico
- 6Savient Pharmaceuticals, Inc., East Brunswick, New Jersey, USA
- 7Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA
- 8Duke Clinical Research Unit, Duke University Medical Center, Durham, North Carolina, USA
- Correspondence to Dr Michael A Becker, 237 East Delaware Pl, Chicago, IL 60611-1713, USA;
- Accepted 9 August 2012
- Published Online First 10 November 2012
Objective To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout.
Methods This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy.
Results Patients (n=149) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained <6 mg/dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence.
Conclusions The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment.
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