Methotrexate (MTX) co-therapy effectively increased pegloticase response rates in patients with uncontrolled gout, according to study results presented at the American College of Rheumatology (ACR) Convergence 2022, held from November 10-14, in Philadelphia, Pennsylvania.
In the randomized clinical trial, Methotrexate to Increase Response Rates in Patients with Uncontrolled GOut Receiving Pegloticase (MIRROR RCT), researchers assessed the efficacy and safety of pegloticase with add-on MTX vs placebo. Uncontrolled gout was defined by the following characteristics: serum uric acid (sUA) level ≥7 mg/dL; urate-lowering therapy (ULT) failure or intolerance; and ≥1 current symptom of gout. Over 52 weeks, patients received biweekly 8 mg pegloticase infusions and add-on therapy with either MTX 15 mg/week or placebo.
The primary efficacy endpoint was treatment response at 1 year, defined by a sUA level <6 mg/dl for ≥80% of weeks 42-52. Tophus resolution and time to sUA monitoring discontinuation were also captured. Adverse events and lab values were monitored throughout the trial duration.
The study cohort comprised 152 patients: 100 in the MTX arm and 52 in the placebo arm. At month 12, 60.0% of the MTX group and 30.8% of the placebo group achieved treatment response (P <.001). Of patients with tophi at baseline, 53.8% in the MTX group vs 31.0% in the placebo group experienced resolution of ≥1 tophus at month 12 (P =.048). Rates of tophus resolution increased in patients in both groups between week 24 and week 52, suggesting that the therapeutic benefits of pegloticase and MTX may extend beyond 6 months.
A greater proportion of the placebo group met criteria for sUA monitoring discontinuation (63.3% vs 22.9%; P <.0001) at week 52. The safety profile was comparable between study groups. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels remained stable across the treatment period. Elevated liver enzyme levels were rare, with 2.2% of the MTX and 2.0% of the placebo groups experiencing elevated ALT, respectively, and 4.3% and 2.0% experiencing elevated AST. No injection site reactions were observed after month 6.
“MIRROR RCT 12-month safety and efficacy further support MTX as co-therapy to pegloticase and showed no IRs [infusion reactions] after treatment Month 6,” the researchers stated. Tophus resolution continued after the 6 month mark, suggesting sustained therapeutic benefits.
Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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Botson J, Saag K, Peterson J, et al. 12-month findings of the randomized, double-blind, placebo-controlled, multicenter, efficacy and safety study of Methotrexate to Increase Response Rates in Patients with Uncontrolled GOut Receiving Pegloticase (MIRROR RCT). Presented at: ACR Convergence 2022; November 10-14; Philadelphia, PA. Abstract #0001.