Adding methotrexate to pegylated enzyme for gout treatment improves remission rate over 52 weeks

Key points:

• Combination therapy with methotrexate and pegase was more effective than pegase alone in relieving gout symptoms over 52 weeks.
• The researchers wrote that tophi regression rates continued to improve with the combination treatment over a 12-month period, indicating continued benefit.

Patients treated with pegase and methotrexate demonstrated higher response rates and fewer discontinuations and were more likely to achieve tophi resolution than patients treated with methotrexate in combination for gout .Data show that patients who received only pegylated enzyme.

“PEGylated enzyme (PEGylated uricase) is often the last remaining treatment option for patients with refractory or uncontrolled gout, which can significantly impact patients’ health and quality of life,” John K. Botson, MD, Alaska Orthopedic Surgeons of Anchorage and colleagues at ACR Open Rheumatology. “Therefore, it is important to maximize the number of patients with sustained reductions in uric acid levels during PEGylation enzyme therapy.

“The MIRROR Randomized Controlled Trial (a randomized, double-blind, placebo-controlled, multicenter, study of the efficacy and safety of methotrexate to improve relief in patients with uncontrolled gout treated with pegylated enzyme (MIRROR RCT)) is the first large-scale double-blind, placebo (PBO)-controlled trial to compare the efficacy and safety of pegylated enzyme in the presence and absence of immune modulation,” they added . “As previously reported, the study met its primary endpoint; pegylated enzyme combined with oral methotrexate (MTX) (15 mg/week) resulted in sustained reductions in PBO combination therapy through month 6 of treatment. The uric acid response rate was significantly higher (71.0% vs. 38.5%).

The aim was to study the long-term safety and effectiveness of pegylated enzyme combined with methotrexate in the treatment of gout, and to compare the long-term safety and effectiveness of gout treatment alone. Botson and colleagues analyzed 12-month data from the MIRROR trial of pegylated enzyme monotherapy. Patients were excluded from the trial if they had a severe bacterial infection, intolerance or contraindications to methotrexate, or one of several viral infections, including HIV or hepatitis B or C. Patients were also excluded due to suboptimal glomerular filtration rate. Elevated liver tests, low blood cell counts, severe high blood pressure, and intolerance to gout attack prevention medications.

Patients with uncontrolled gout were randomly assigned in a 2:1 ratio to receive 8 mg of pegolase infusion every two weeks along with weekly infusions of 15 mg of methotrexate or placebo. The primary efficacy endpoint was the proportion of patients responding to treatment at 6 months. Meanwhile, secondary endpoints include the proportion of patients who respond to treatment at 12 months and the proportion of patients who have complete resolution of any tophi present at baseline.

A total of 152 patients were included in the study, 100 of whom received methotrexate plus PEGylation. According to the researchers, 60% of patients who received the combination therapy achieved treatment response at 12 months compared with 30.8% in the single-therapy group (difference = 29.1%; 95% CI, 13.2% to 44.9 %). Additionally, 53.8% of patients who received the combination therapy had complete resolution of one or more tophi compared with 31% of patients who received pegase alone (difference = 22.8%; 95% CI, 1.2% to 44.4%). Safety was similar across groups.

They write: “Twelve-month results from the MIRROR RCT trial confirm that combination therapy with pegase plus MTX is more durable in reducing uric acid response rates through 12 months compared with pegase monotherapy. “Additionally, visible tophi continued to resolve after week 24 of PEGase treatment, suggesting that many patients may benefit from treatment beyond 6 months.”

“As previously reported, the incidence of (infusion reactions (IR)) was significantly lower in patients treated with MTX during the first 6 months of treatment (4.2% vs. 30.6%), but the safety profile was otherwise Similar,” they added. “Notably, no IR occurred in either treatment group after week 24, and the safety profile remained similar between the MTX and PBO combination groups through week 52.”