Gout is a painful and chronic form of arthritis that affects millions of people worldwide. While there are medications available to manage gout symptoms, some patients experience uncontrolled gout, where conventional treatments fail to provide adequate relief. “Pegloticase (PEGylated uricase) is often the last remaining treatment option for patients with refractory or uncontrolled gout, which can markedly impact patient health and quality of life,” researchers from the MIRROR RCT study wrote, which was published in ACR Open Rheumatology. In their study, they aimed to evaluate the safety and efficacy of combining methotrexate (MTX) with pegloticase to further enhance treatment outcomes.
MIRROR RCT was a randomized, double-blind, placebo-controlled, multicenter trial that spanned over 12 months. The study included patients with uncontrolled gout who had a serum urate (SU) level of at least 7 mg/dL, had failed or were intolerant to oral urate-lowering therapy, and presented with 1 or more gout symptoms such as tophi (uric acid deposits), frequent flares, or gouty arthropathy (joint damage due to gout).
The participants were randomly assigned to 1 of 2 groups: one receiving pegloticase infusions every 2 weeks along with oral MTX (15 mg/week), and the other receiving pegloticase infusions with a placebo. The primary endpoint of the study was the proportion of responders, defined as patients achieving an SU level below 6 mg/dL for at least 80% of the examined month, at month 6. Secondary endpoints included response rates at months 9 and 12, resolution of tophi, mean SU reduction, and the duration of pegloticase treatment.
The results of the study revealed significant benefits of combining MTX with pegloticase. At month 12, the response rate among patients receiving the combination therapy was 60.0% compared with 30.8% in the placebo group, representing a substantial difference of 29.1%. Moreover, the rate of discontinuation of pegloticase due to elevated SU levels was much lower in the MTX group (22.9%) compared with the placebo group (63.3%). Additionally, the combination therapy demonstrated improved resolution of tophi, with 53.8% of patients in the MTX group achieving complete resolution compared with 31.0% in the placebo group at week 52.
The findings also indicated that the benefits of the combination therapy continued to increase beyond the sixth month, suggesting a sustained therapeutic effect. The pharmacokinetic and immunogenicity data showed that the exposure to pegloticase was higher, and the development of antibodies against the drug was lower when administered with MTX . Importantly, the safety profile of the combination therapy was comparable to that of pegloticase alone, with no infusion reactions reported after 24 weeks.
Per the researchers, “In conclusion, the 12-month results from the MIRROR RCT trial confirm increased urate-lowering response rate durability through month 12 of pegloticase [plus] MTX cotherapy versus pegloticase monotherapy.”
Source: ACR Open Rheumatology
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