TY - JOUR 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 DO - 10.3899/jrheum.200460 SP - jrheum.200460 AU - John K. Botson AU - John R.P. Tesser AU - Ralph Bennett AU - Howard M. Kenney AU - Paul M. Peloso AU - Katie Obermeyer AU - Brian LaMoreaux AU - Michael E. Weinblatt AU - Jeff Peterson Y1 - 2020/09/15 UR - http://www.jrheum.org/content/early/2020/09/10/jrheum.200460.abstract N2 - 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. ER -