Long-term data from the MIRROR randomized controlled trial of Krystexxa injection with methotrexate published in ACR Open Rheumatology

“Publication of these 12-month data reinforces key findings shown at Month 6, including the durability of urate-lowering response, reduced infusion reactions and reduced immunogenicity of pegloticase when co-administered with methotrexate,” said Kenneth Saag, M.D., author and Director of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham. “Encouragingly, urate-lowering efficacy with the co-therapy approach was sustained over time with continued treatment in most patients. Further, the number of patients seeing complete resolution of at least one tophus markedly increased between Month 6 and Month 12 of treatment.”

This analysis extends the MIRROR randomized controlled trial body of data through Month 12 of treatment, showing a largely sustained patient response rate and similar safety profile as the Month 6 findings: i. Improvement in the patient response rate remained nearly 30 percentage points higher with methotrexate co-therapy during Month 12 (p<0.001): of patients randomized to receive krystexxa with methotrexate, 60.0% (60 of 100) achieved a serum urate (su) level less than 6 mg dl for at least 80% of the time during month 12 (weeks 49-52) versus 30.8% (16 of 52) of those randomized to receive krystexxa with placebo. ii. a 23 percentage-point increase in the complete resolution of at least one tophus at month 12 (p="0.048):" among patients with tophi at baseline, 53.8% (28 of 52) in the krystexxa with methotrexate group had complete resolution of at least one tophus with no new tophus formation and no single tophus progression at week 52 (month 12), compared with 31.0% (9 of 29) in the krystexxa with placebo group. iii. consistent pharmacokinetic and immunogenicity findings through month 12: data were consistent with month 6 findings, indicating higher krystexxa serum concentrations during treatment that resulted from lower krystexxa immunogenicity in those who received co-administration with methotrexate. iv. all health assessment questionnaire (haq) measures progressively decreased during treatment in a clinically meaningful way: the least-square mean change from baseline in haq disability index was - 0.35 in patients receiving krystexxa with methotrexate and -0.31 in patients receiving krystexxa with placebo at week 52. the improvement in both groups was clinically meaningful (meaningful clinically important difference [mcid]: - 0.22) but was not significantly different between groups (difference: - 0.04 [-0.21, 0.13], p="0.6287)." haq pain and health scores also progressively and meaningfully improved during treatment (mcid: 10). at week 52, the krystexxa with methotrexate group had greater improvement in both haq pain (least-square mean: -31.03 vs. -22.59; treatment difference: -8.43 [-15.88, -0.97], p="0.0272)" and haq health (least-square mean: -28.85 vs. -18.69; treatment difference: -10.16 [-18.84, -.48], p="0.0222)" compared to krystexxa with placebo.

“Given the damage that uncontrolled gout can cause to bones and joints, as well as its significant impact on a person’s daily life, it is crucial to provide data that demonstrate how a co-treatment approach can quickly lower a patient’s serum urate level and sustain it over time,” said Brian LaMoreaux, M.D., M.S., senior medical director, Horizon. “As clinicians, when we commit ourselves to improving the quality of care provided to people who live with uncontrolled gout, we’re also working to improve their quality of life.”