MTX + Pegloticase Combo FDA Approved Save

Horizon has announced that the U.S. Food and Drug Administration (FDA) has approved the expanded labeling of pegloticase (Krystexxa) injection to be co-administered with methotrexate (MTX), to improve response rates in patients with uncontrolled gout.

FDA approval is based on the MIRROR randomized controlled trial, which showed significant improvement and sustained patient response when MTX plus pegloticase (PEG) was compared to PEG alone. The trial showed a >30%increase in efficacy, with a significant reduction in infusion reactions from 31% to 4%, when MTX + PEG was used. 

In the MIRROR study, patients received either PBO or MTX 15 mg/weekfor four weeks, and then PEG was added to each arm for a total of 52 weeks. The primary endpoint was defined as the proportion of serum uric acid (sUA) responders during Month 6 (defined as sUA less than 6 mg/dL at least 80% of the time). At the end of 6 months, the results favored MTX + PEG (71% vs 39%; p<0.0001) achieving a sUA less than 6 mg/dL at least 80% of the time during Month 6).

Complete resolution of at least one tophus also favored the combo group, 54% vs vs 31% (p=0.048) at month 12.

The updated package insert states:

• The recommended dosage is KRYSTEXXA 8 mg every two weeks given as an intravenous infusion, co-administered with weekly methotrexate 15 mg orally.
• KRYSTEXXA alone may be used in patients for whom methotrexate is contraindicated or not clinically appropriate.
• Methotrexate with folic acid or folinic acid supplementation should be initiated at least 4 weeks prior to initiating, and throughout treatment with KRYSTEXXA.
• Discontinue oral urate-lowering agents before starting KRYSTEXXA.
• Monitor serum uric acid levels before each infusion.
• Pre-medicate patients with antihistamines and corticosteroids.
• KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia.