Pegloticase and Methotrexate cotherapy scores over Pegloticase monotherapy inTreatment of gout

A recent study published in the ACR Open Rheumatology assessed the 12-month outcomes of pegloticase combined with methotrexate (MTX) versus pegloticase with a placebo (PBO) in a double-blind trial and found the novel treatment regimen to show remarkable safety and efficacy.

The trial enrolled patients with uncontrolled gout, characterized by a serum urate level (SU) of ≥7 mg/dl, a history of oral urate-lowering therapy failure or intolerance, and the presence of one or more gout symptoms (such as tophi or gouty arthropathy). Participants were randomized 2:1 to receive either pegloticase (administered via an 8-mg infusion every two weeks) alongside blinded MTX (oral 15 mg/week) or a placebo for 52 weeks. Efficacy was gauged by several endpoints, including the proportion of responders, resolution of tophi, mean SU reduction, and the duration of pegloticase therapy. Safety was closely monitored through adverse event reporting and laboratory assessments.

The most striking finding of the study was the significantly higher response rate at month 12 in patients treated with the pegloticase and MTX combination (60.0% vs. 30.8% in the placebo group). Moreover, the pegloticase plus MTX group experienced substantially fewer SU discontinuations (22.9% vs. 63.3% in the placebo group). Tophi resolution was also notably more pronounced in the MTX group, with 53.8% achieving complete resolution at week 52 compared to 31.0% in the placebo group. Importantly, the therapeutic benefits of this combined treatment persisted beyond month 6.

The study also demonstrated that pegloticase's exposure and immunogenicity were enhanced when administered alongside MTX, with a comparable safety profile. Notably, no infusion reactions were observed after the 24-week mark.

This breakthrough could significantly improve the quality of life for countless individuals battling this painful condition, heralding a new era in gout management. Further research and clinical trials will likely build upon these exciting results, paving the way for more effective treatments for gout patients in the future.

Reference:

Botson, J. K., Saag, K., Peterson, J., Obermeyer, K., Xin, Y., LaMoreaux, B., Padnick‐Silver, L., Verma, S., Grewal, S., Majjhoo, A., Tesser, J. R. P., & Weinblatt, M. E. (2023). A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12‐Month Findings. In ACR Open Rheumatology (Vol. 5, Issue 8, pp. 407–418). Wiley. https://doi.org/10.1002/acr2.11578