A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings.

Autor: Botson JK; Orthopedic Physicians Alaska, Anchorage, Alaska., Saag K; University of Alabama at Birmingham., Peterson J; Western Washington Arthritis Clinic, Bothell, Washington., Parikh N; Napa Research Center, Pompano Beach, Florida., Ong S; MD Medical Research, Oxon Hill, Maryland., La D; Keck USC Medical Center, Los Angeles, California., LoCicero K; GCP Clinical Research, LLC, Tampa, Florida., Obermeyer K; Horizon Therapeutics plc, Deerfield, Illinois., Xin Y; Horizon Therapeutics plc, Deerfield, Illinois., Chamberlain J; Horizon Therapeutics plc, Deerfield, Illinois., LaMoreaux B; Horizon Therapeutics plc, Deerfield, Illinois., Verma S; Horizon Therapeutics plc, Deerfield, Illinois., Sainati S; Horizon Therapeutics plc, Deerfield, Illinois., Grewal S; East Bay Rheumatology Medical Group Inc., San Leandro, California., Majjhoo A; Shores Rheumatology, St. Clair Shores, Michigan., Tesser JRP; Arizona Arthritis & Rheumatology Associates PC, Phoenix., Weinblatt ME; Brigham and Women's Hospital, Boston, Massachusetts.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2023 Feb; Vol. 75 (2), pp. 293-304. Date of Electronic Publication: 2022 Dec 16.
DOI: 10.1002/art.42335
Abstrakt: Objective: To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo-controlled, double-blind trial.
Methods: This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate <40 ml/minute/1.73 m 2 . Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80% of visits during weeks 20-24). Efficacy was evaluated in all randomized patients (intent-to-treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose.
Results: A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between-group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P < 0.0001 for between-group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P < 0.001). Antidrug antibody positivity was also lower in the MTX group.
Conclusion: MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.
(© 2022 Horizon Therapeutics PLC. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Databáze: MEDLINE
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