Adding methotrexate to pegloticase for gout increases response rate through 52 weeks
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Key takeaways:
- Combination therapy with methotrexate and pegloticase was more impactful at resolving gout symptoms than pegloticase alone through 52 weeks.
- Tophi resolution continued to increase with combination therapy through 12 months, suggesting continued benefit, the researchers wrote.
Patients who receive pegloticase alongside methotrexate for gout demonstrate higher response rates and fewer discontinuations, and were more likely to achieve tophi resolution, vs. those treated with pegloticase alone, according to data.
“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,” John K. Botson, MD, of Orthopedic Physicians Alaska, in Anchorage, and colleagues wrote in ACR Open Rheumatology. “Therefore, maximizing the number of patients who have sustained lowering of urate levels during pegloticase therapy is important.
“The MIRROR randomized controlled trial (a 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]) was the first large-scale double-blind, placebo (PBO)-controlled trial to compare pegloticase efficacy and safety in the presence and absence of immunomodulation head-to-head,” they added. “As previously reported, the study met its primary end point; pegloticase administered with oral methotrexate (MTX) (15 mg/week) versus PBO as co-therapy resulted in a significantly higher rate of sustained urate-lowering response during treatment month 6 (71.0% vs. 38.5%).”
To investigate the long-term safety and efficacy of combination therapy with pegloticase plus methotrexate for gout, vs. pegloticase monotherapy, Botson and colleagues analyzed 12-month data from the MIRROR trial. Patients were excluded from the trial if they had a serious bacterial infection, an intolerance or contraindication to methotrextae, or one of several viral infections, including HIV or hepatitis B or C. Patients were also excluded for less-than-satisfactory glomerular filtration rates, elevated liver tests, low blood cell numbers, serious hypertension and an intolerance for gout flare prophylaxis medications.
Patients with uncontrolled gout were randomized 2:1 to receive an infusion of pegloticase 8 mg every 2 weeks alongside either 15 mg of methotrexate or placebo every week. The primary efficacy endpoint was the proportion of patients who responded to therapy at 6 months. Secondary endpoints, meanwhile, included the proportion of patients who responded to therapy at 12 months as well as the proportion of patients achieving total resolution of any tophi present at baseline.
The study included a total of 152 patients, 100 of whom received methotrexate in combination with pegloticase. Among the patients receiving combination therapy, 60% achieved treatment response at 12 months, compared with 30.8% in the monotherapy group (difference = 29.1%; 95% CI, 13.2% to 44.9%), according to the researchers. In addition, the complete resolution of one or more tophi occurred in 53.8% of patients who received combination therapy, compared with 31% of those who received pegloticase alone (difference = 22.8%; 95% CI, 1.2% to 44.4%). Safety profiles were similar across groups.
“The 12-month results from the MIRROR RCT trial confirm increased urate-lowering response rate durability through month 12 of pegloticase plus MTX co-therapy versus pegloticase monotherapy,” they wrote. “Additionally, resolution of visible tophi continued to occur past week 24 of pegloticase treatment, indicating that many patients may benefit from a treatment course longer than 6 months.
“As previously reported, the [infusion reaction (IR)] rate was substantially lower in patients cotreated with MTX (4.2% vs. 30.6%) during the first 6 months of therapy, with an otherwise similar safety profile,” they added. “Of note, no IRs occurred in either treatment group following week 24, and the safety profile remained similar between the MTX and PBO co-therapy groups through week 52.”
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