Investigator Dr. John Botson spoke on the phase 4 MIRROR study that supported the FDA approval for pegloticase combined with methotrexate for patients with uncontrolled gout.
One of the lead investigators on the phase 4 MIRROR study that supported the US Food and Drug Administration (FDA) approval for pegloticase (Krystexxa) combined with methotrexate (MTX) spoke about how the treatment can help patients with uncontrolled gout.
Results from the clinical trial showed that 71% of patients who received the combination therapy of pegloticase and methotrexate achieved a complete response over 6 months. This was compared with 38.5% in the group of patients who received pegloticase plus placebo.
John Botson, MD, RPh, Director of Rheumatology, Orthopedic Physicians Alaska, was excited to discuss the long road of research that led to the success of the combination therapy.
Pegloticase has been used for years to treat gout, but patients who receive the infusions always have the potential to develop antibodies against the drug, rendering it less or ineffective. They also experience infusion reactions.
"If we use methotrexate, which is a medicine we use for other rheumatologic diseases, that actually stops the body from making these antibodies against the drug," he explained, "and then it allows it to work better or work longer, so that the person can actually finish the course."
The investigators administered a low dose of methotrexate through an IV every 2 weeks for a month prior to the patients' pegloticase infusions.
"It works to drop the serum uric acid down, which we know is related to gout, to essentially undetectable, and it's working," Botson said. "So, really a way to get the person better control their gout and get rid of this tuffaceous material and uric acid buildup that they've had in their bodies."
The primary endpoint was the proportion of treatment responders at month 6. This included serum uric acid (sUA) of less than 6 mg/dL for at least 80% of the time when patients were evaluated at weeks 20-24.
A very low dose of methotrexate was used to achieve these results. According to Botson, patients didn't experience the adverse events that are generally thought to be associated with drug.
"Even in those patients that may be at higher risk for liver toxicities or other problems from the methotrexate, we really don't see it in this study," Botson explained. "And one of the secondary endpoints we looked at was, you didn't see any increased risk from being on methotrexate or not. So, none of these methotrexate-related potential side effects showed up with this course of treatment."