Kenneth Saag, MD: Pegloticase and Methotrexate Concomitant Therapy Demonstrates Continued Benefits for Gout Treatment

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At the 12-month mark, response rate in patients with uncontrolled gout was significantly higher in those treated with pegloticase and concomitant methotrexate when compared with placebo.

Findings from the phase 4, randomized, double-blind, parallel-group, placebo-controlled, multicenter MIRROR trial demonstrated pegloticase injection plus methotrexate was an effective and sustainable long-term treatment strategy for patients with uncontrolled gout.1 In an interview with HCPLive Rheumatology, Kenneth Saag, MD, lead investigator of the trial and director of clinical immunology and rheumatology at the University of Alabama at Birmingham, discussed the clinical significance of these results.

Long-term use of pegloticase may result in patients developing immunity to the drug, reducing its effectiveness and potentially leading to adverse reactions. Saag and his team hypothesized that combining pegloticase with methotrexate could prolong the drug's efficacy and improve patient outcomes.

The study was an extension of the original research, aimed at investigating the long-term effects of this combined therapy to further understand its benefits and potential impact on patient care. Ultimately, 152 patients were randomized 2:1 to receive pegloticase (8 mg infusion every 2 weeks) with blinded methotrexate (oral 15 mg/week) or placebo for 52 weeks.

“The team's motivation to assess the long-term outcomes of pegloticase in combination with methotrexate stems from the drug's significant efficacy in treating advanced gout, particularly in patients who have not responded well to other treatments,” said Saag. “Severe gout can lead to the formation of uric acid deposits known as tophi around the joints, causing disability and potential complications like ulcers and infections. For patients with severe gout, conventional treatments are often slow in removing these tophi, making pegloticase a game-changer due to its effectiveness in resolving the condition.”

At the 12-month mark, response rate was significantly higher in patients treated with concomitant methotrexate when compared with placebo. The co-therapy group also reported fewer discontinuations and more complete resolution of ≥1 tophi.

Saag emphasized it is crucial for patients to take the condition seriously, seek appropriate medical care, and be aware of the right treatment and lifestyle adjustments. With these factors in mind, gout can be effectively managed and even reversed, leading to improved health outcomes.

This transcript was edited for clarity.


Pine, L. (2023c, July 6). Study demonstrates increased benefits of pegloticase and methotrexate cotherapy for uncontrolled gout. HCP Live.