Dissociation Between Clinical Benefit and Persistent Urate Lowering in Patients with Chronic Refractory Gout Treated with Pegloticase.

OBJECTIVE: To assess clinical benefit in patients with chronic refractory gout who did not meet the protocol-defined criteria of responders to pegloticase. METHODS: This analysis used results from 2 randomized controlled trials (ClinicalTrials.gov: NCT00325195, NCT01356498) to assess the clinical efficacy in responders and nonresponders to treatment (8 mg of pegloticase every 2 weeks). Serum urate was measured before each infusion and the following were recorded: assessment of gout flares, tophus reduction, patient's global assessment (PtGA), tender and swollen joints (TJC and SJC), pain using a 100-mm visual analog scale, and a variety of patient-reported outcomes [Medical Outcomes Study Short Form-36 questionnaire physical component summary score and arthritis-specific health index (ASHI) score]. RESULTS: The analysis included 36 persistent urate responders, 49 nonresponders, and 43 patients who received placebo. Results for both responders and nonresponders indicated significant reduction in tophi and improvements from baseline in PtGA, TJC, SJC, pain, and ASHI. No significant improvements were observed in the patients who received placebo. CONCLUSION: Chronic refractory gout patients not achieving protocol-defined persistent urate lowering still achieve significant clinical benefits with pegloticase treatment, suggesting that transient reduction in serum urate may result in sustained clinical benefit.