A Randomized, Placebo‐Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings. Issue 2 (16th December 2022)

• Record Type: Journal Article
• Authors: Botson, John K.; Saag, Kenneth; Peterson, Jeff; Parikh, Naval; Ong, Stephen; La, Dan; LoCicero, Karon; Obermeyer, Katie; Xin, Yan; Chamberlain, Jason; LaMoreaux, Brian; Verma, Supra; Sainati, Stephen; Grewal, Suneet; Majjhoo, Amar; Tesser, John R. P.; Weinblatt, Michael E.
• Is Part Of: Arthritis & rheumatology. Volume 75:Issue 2(2023)
• Page Start: 293
• Page End: 304
• Publication Date: 2022-12-16
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.42335
• Languages: English
• ISSNs: 2326-5191

Abstract

Abstract : 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.