RT Journal Article SR Electronic T1 Pegloticase in combination with methotrexate in patients with uncontrolled gout: A multicenter, open-label study (MIRROR) JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP jrheum.200460 DO 10.3899/jrheum.200460 A1 John K. Botson A1 John R.P. Tesser A1 Ralph Bennett A1 Howard M. Kenney A1 Paul M. Peloso A1 Katie Obermeyer A1 Brian LaMoreaux A1 Michael E. Weinblatt A1 Jeff Peterson YR 2020 UL http://www.jrheum.org/content/early/2020/09/10/jrheum.200460.abstract AB Objective To examine the efficacy and safety of pegloticase in combination with methotrexate in patients with uncontrolled gout in an exploratory, open-label clinical trial (NCT03635957) prior to a randomized, controlled trial. Methods A multicenter, open-label, efficacy and safety study of pegloticase with methotrexate cotreatment was conducted in patients with uncontrolled gout. Patients were administered oral methotrexate (15 mg/week) and folic acid (1 mg/day) 4 weeks prior to and throughout pegloticase treatment. The primary study outcome was the proportion of responders, defined as sUA <6 mg/dL for ≥80% of the time during month 6 (weeks 20, 22, and 24). All analyses were performed on a modified intent-to-treat population, defined as patients who received ≥1 pegloticase infusion. Results Seventeen patients were screened and 14 patients (all men, average age: 49.3 ± 8.7 years) were enrolled. On Day 1, mean sUA was 9.2 ± 2.5 mg/dL and 12 of the 14 patients had visible tophi. At the 6 month timepoint, 11/14 (78.6%, 95%CI 49.2-95.3%) met the responder definition, with 3 patients discontinuing after meeting protocol-defined treatment discontinuation rules (pre-infusion sUA values greater than 6 mg/dL at 2 consecutive scheduled visits). All patients tolerated methotrexate. No new safety concerns were identified. Conclusion In this study, an increased proportion of patients maintained therapeutic response at 6 months when treated concomitantly with methotrexate and pegloticase when compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of methotrexate or placebo with pegloticase to validate these open label findings.