{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:43:36Z","timestamp":1790981016804,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019637","name":"Horizon Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo\u2010controlled, double\u2010blind trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included adults with uncontrolled gout, defined as serum urate \u22657 mg\/dl, oral urate\u2010lowering therapy failure or intolerance, and presence of ongoing gout symptoms including \u22651 tophus, \u22652 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 &lt;40 ml\/minute\/1.73 m<jats:sup>2<\/jats:sup>. Patients were randomized 2:1 to 52\u2009weeks 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 &lt;6 mg\/dl for \u226580% of visits during weeks 20\u201324). Efficacy was evaluated in all randomized patients (intent\u2010to\u2010treat population), and safety was evaluated in all patients receiving \u22651 blinded MTX or placebo dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001 for between\u2010group 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 \u22651 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]) (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Antidrug antibody positivity was also lower in the MTX group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42335","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T13:14:47Z","timestamp":1663074887000},"page":"293-304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["A Randomized, <scp>Placebo\u2010Controlled<\/scp> Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings"],"prefix":"10.1002","volume":"75","author":[{"given":"John K.","family":"Botson","sequence":"first","affiliation":[{"name":"Orthopedic Physicians Alaska  Anchorage Alaska"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Saag","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Peterson","sequence":"additional","affiliation":[{"name":"Western Washington Arthritis Clinic  Bothell Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naval","family":"Parikh","sequence":"additional","affiliation":[{"name":"Napa Research Center  Pompano Beach Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Ong","sequence":"additional","affiliation":[{"name":"MD Medical Research  Oxon Hill Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"La","sequence":"additional","affiliation":[{"name":"Keck USC Medical Center  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karon","family":"LoCicero","sequence":"additional","affiliation":[{"name":"GCP Clinical Research, LLC  Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Obermeyer","sequence":"additional","affiliation":[{"name":"Horizon Therapeutics plc  Deerfield Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xin","sequence":"additional","affiliation":[{"name":"Horizon Therapeutics plc  Deerfield Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Chamberlain","sequence":"additional","affiliation":[{"name":"Horizon Therapeutics plc  Deerfield Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7521-241X","authenticated-orcid":false,"given":"Brian","family":"LaMoreaux","sequence":"additional","affiliation":[{"name":"Horizon Therapeutics plc  Deerfield Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supra","family":"Verma","sequence":"additional","affiliation":[{"name":"Horizon Therapeutics plc  Deerfield Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Sainati","sequence":"additional","affiliation":[{"name":"Horizon Therapeutics plc  Deerfield Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suneet","family":"Grewal","sequence":"additional","affiliation":[{"name":"East Bay Rheumatology Medical Group Inc.  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