In patients with chronic refractory gout whose serum urate (SU) was not maintained at ≤6 mg/dL, adding an additional tolerizing dose of pegloticase between the first and second biweekly administrations showed an overall response rate of 44%, according to results from TRIPLE, a multi-center, open-label trial. In the trial, background urate lowering therapy was discontinued and patients were treated with three weekly doses of pegloticase 8 mg followed by biweekly administration of pegloticase 8 mg for a total of 10 doses in 17 weeks. SU was measured immediately before each dose and after the first administration, and continued dosing was only permitted if the SU was ≤6 mg/dL. Trough serum pegloticase levels were measured before each dose. Standard infusion prophylaxis and gout flare prophylaxis were required. The primary outcome was the maintenance of SU at ≤6 mg/dL throughout the treatment period. Researchers found that responders had significantly higher trough levels of pegloticase than nonresponders 1 week after the initial infusion that persisted throughout the trial. Fourteen of 19 subjects (73.7%) with trough pegloticase levels >1.22 mg/mL at 1 week were responders to treatment whereas only 6 of 19 patients (31.6%) with trough levels ≤1.22 mg/mL at 1 week were responders (Chi square test with continuity correction). Based on the observation that pegloticase levels predicted responsiveness at 1 week post-infusion, the study team concluded that pegloticase serum levels after the initial dose may predict subsequent persistent responsiveness and provide guidance regarding adjustment/continuation of treatment.
