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A Randomized, <scp>Placebo‐Controlled</scp> Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings

Authors :
John K. Botson
Kenneth Saag
Jeff Peterson
Naval Parikh
Stephen Ong
Dan La
Karon LoCicero
Katie Obermeyer
Yan Xin
Jason Chamberlain
Brian LaMoreaux
Supra Verma
Stephen Sainati
Suneet Grewal
Amar Majjhoo
John R. P. Tesser
Michael E. Weinblatt
Source :
Arthritis & Rheumatology. 75:293-304
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

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.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 rate40 ml/minute/1.73 mA 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.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.

Details

ISSN :
23265205 and 23265191
Volume :
75
Database :
OpenAIRE
Journal :
Arthritis & Rheumatology
Accession number :
edsair.doi.dedup.....de07f758f4a597cfe4ec558774b34646
Full Text :
https://doi.org/10.1002/art.42335