FDA Approves Combination Pegloticase and Methotrexate for Refractory Gout 

Maiya Focht

July 11, 2022

The US Food and Drug Administration (FDA) has approved concomitant use of the biologic pegloticase (Krystexxa) and methotrexate to lower serum uric acid levels (sUA) in patients with chronic gout.

Pegloticase, which has been available for 12 years, is a pegylated uric acid-specific enzyme that lowers sUA by converting it to allantoin.

Though pegloticase is effective in treating chronic gout in patients refractory to conventional treatment, approximately 92% of patients develop antibodies against the drug, resulting in reduced efficacy.

Based on the immunomodulatory effects of methotrexate, researchers of the randomized, placebo-controlled MIRROR trial sought to determine whether combination treatment of pegloticase with methotrexate (multiple brands) would prevent the development of anti-drug antibodies.

Findings from the phase 4 trial found that co-administration of pegloticase and methotrexate reduced the formation of new anti-PEG antibodies. In the group receiving methotrexate and pegloticase, 23.2% (22 out of 95) of patients had an increase in anti-PEG antibodies compared with 50% (24 of 48) in the pegloticase plus placebo group, according to recent company press release.

Nearly three quarters (71%) of participants in the group pretreated with methotrexate, followed by combination pegloticase-methotrexate, had sUA levels that dopped to below 6 mg/dL during the 52-week study. By comparison, 38.5% of participants in the pegloticase and placebo group reached the endpoint. Though gout flare occurred in both groups, methotrexate did not appear to increase the risk for adverse events or gout flare.

The study, led by John Botson, MD, RPh, CCD, a rheumatologist in Anchorage, Alaska, concluded that these measurements demonstrated a significant improvement from traditional pegloticase-only treatment of gout. "This trial confirms not only improved efficacy but improved safety in patients treated with pegloticase in combination with methotrexate 15 mg orally once weekly," Botson said last month in an interview with Medscape.

The study was funded by Horizon. Botson reports receiving research support from Horizon and Radius Health, and speaker fees from AbbVie, Amgen, Aurinia, ChemoCentryx, Horizon, Eli Lilly, and Novartis.


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