PT  - JOURNAL ARTICLE
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
TI  - Pegloticase in Combination With Methotrexate in Patients With Uncontrolled Gout: A Multicenter, Open-label Study (MIRROR)
AID  - 10.3899/jrheum.200460
DP  - 2020 Sep 15
TA  - The Journal of Rheumatology
PG  - jrheum.200460
4099  - http://www.jrheum.org/content/early/2021/02/10/jrheum.200460.short
4100  - http://www.jrheum.org/content/early/2021/02/10/jrheum.200460.full
AB  - Objective To examine the efficacy and safety of pegloticase in combination with methotrexate (MTX) in patients with uncontrolled gout in an exploratory, open-label clinical trial (ClinicalTrials.gov: NCT03635957) prior to a randomized, controlled trial. Methods A multicenter, open-label efficacy and safety study of pegloticase with MTX co-treatment was conducted in patients with uncontrolled gout. Patients were administered oral MTX (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 serum uric acid (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 (preinfusion sUA values > 6 mg/ dL at 2 consecutive scheduled visits). All patients tolerated MTX. 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 MTX and pegloticase as compared to the previously reported 42% using pegloticase alone. These results support the need for a randomized study of MTX or placebo with pegloticase to validate these open-label findings.