John K Botson1, John R P Tesser2, Ralph Bennett2, Howard M Kenney3, Paul M Peloso4, Katie Obermeyer4, Brian LaMoreaux4, Michael E Weinblatt5, Jeff Peterson6. 1. J.K. Botson, MD, RPh, Orthopedic Physicians Alaska, Anchorage, Alaska; jbotson@opaak.com. 2. J.R. Tesser, MD, R. Bennett, MD, Arizona Arthritis & Rheumatology Associates, P.C., Phoenix, Arizona. 3. H.M. Kenney, MD, Arthritis Northwest, PLLC, Spokane, Washington. 4. P.M. Peloso, MD, MSc, K. Obermeyer, MS, B. LaMoreaux, MD, MS, Horizon Therapeutics, Lake Forest, Illinois. 5. M.E. Weinblatt, MD, Brigham and Women's Hospital, Boston, Massachusetts. 6. J. Peterson, MD, Western Washington Arthritis Clinic, Bothell, Washington, USA.
Abstract
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.
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.
Authors: John K Botson; Herbert S B Baraf; Robert T Keenan; John Albert; Karim R Masri; Jeff Peterson; Christianne Yung; Brigid Freyne; Mona Amin; Abdul Abdellatif; Nehad Soloman; N Lawrence Edwards; Vibeke Strand Journal: Curr Rheumatol Rep Date: 2022-02-15 Impact factor: 4.592
Authors: John K Botson; John R P Tesser; Ralph Bennett; Howard M Kenney; Paul M Peloso; Katie Obermeyer; Yang Song; Brian LaMoreaux; Lin Zhao; Yan Xin; Jason Chamberlain; Srini Ramanathan; Michael E Weinblatt; Jeff Peterson Journal: Arthritis Res Ther Date: 2022-08-25 Impact factor: 5.606
Authors: Christopher Jenkins; Jennifer H Hwang; Jeffrey B Kopp; Cheryl A Winkler; Sung Kweon Cho Journal: Front Pharmacol Date: 2022-08-23 Impact factor: 5.988