Pegloticase plus methotrexate increases response rates in uncontrolled gout cases
Presenter: John Botson, MD, Orthopedic Physicians Alaska, Anchorage, AK
A summary of 12-Month Findings of the Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled GOut Receiving Pegloticase (MIRROR RCT). Abstract No. 0001. Presented November 12, 2022.
A combination of pegloticase and methotrexate continues to sustain high rates of urate-lowering response in patients with uncontrolled gout at 12 months.
Pegloticase (pegylated uricase) has been shown to lower serum uric acid in patients with gout, but anti-drug antibodies develop in the vast majority of patients, limiting urate-lowering response and leading to high infusion-reaction risks, according to John Botson, MD, Orthopedic Physicians Alaska, Anchorage, AK. However, adding methotrexate can prevent anti-drug antibodies development against biologics while maintaining efficacy, he said.
The MIRROR randomized controlled trial examined the safety and efficacy of pegloticase combined with methotrexate versus placebo. During month 6, the sustained urate-lowering rate, the primary endpoint, was significantly higher in the methotrexate group (71%) compared with the placebo group (38.5%), with a lower infusion reaction rate (4.2% vs 30.6%, respectively). The safety profile was similar in both groups. These findings were related to higher pegloticase exposure and lower anti-pegloticase antibody incidence in the methotrexate group, he said.
Botson reported MIRROR findings through treatment month 12. The efficacy, safety, pharmacoki-netics, and immunogenicity were compared for pegloticase (8 mg biweekly infusion) administered as cotherapy with methotrexate (oral 15 mg/wk) versus placebo for 52 weeks in 152 patients with uncontrolled gout.
After a 2-week tolerance test, patients were randomized to either methotrexate (100 patients) or placebo (52 patients), initiating blinded cotherapy with methotrexate or placebo 4 weeks before pegloticase infusion. The urate-lowering response rate during month 12 was 60% in the metho-trexate group versus 30.8% in the placebo group (P < .001). Also, 22.9% of the methotrexate group and 63.3% of the placebo group met serum uric acid discontinuation criteria. Median time to dis-continuation was not estimable in methotrexate recipients (too few to estimate) and 69 days in placebo recipients. At week 52, for patients with tophi at baseline, 53.8% (28/52) versus vs 31% (9/29), respectively, had complete resolution of at least 1 tophus (P = .048) which was higher than at week 24 (34.6% vs 13.8%).
Key immunogenicity findings show “the methotrexate group developed new anti-pegloticase anti-bodies at a lower rate, and had higher rates of urate-lowering efficacy and a lower rate of infusion reactions in the absence and presence of new anti-pegloticase antibodies,” Botson said. The infu-sion reaction rate was 32.1% with methotrexate versus 13.3% with placebo with no infusion reac-tions occurring after week 24.
The safety profile was similar between the treatment groups, with all immune responses occurring within 24 weeks. The most common adverse event was gout flares, occurring in about 70% of pa-tients. The serious adverse event rate was similar in both arms (13.5% for methotrexate vs 10.2% for placebo).
In conclusion, Botson said, “The MIRROR trial demonstrated a significantly higher rate of sustained urate-lowering response through month 12 in patients cotreated with pegloticase and methotrex-ate. Tophi continued to resolve through week 52, indicating continued therapeutic benefit beyond month 6. No new safety concerns were identified.”
“The trial confirms the improved efficacy and safety of pegloticase therapy when coadministered with methotrexate.”
References
Botson J, Saag K, Peterson J, et al. OP0171 a randomized, double blind, placebo controlled, multi-center, study of methotrexate combined with pegloticase in patients with uncontrolled gout. Ann Rheum Dis 2022; 81(suppl 1):112—113.doi.org/10.1136/annrheumdis-2022-eular.2949
Xin Y, Song Y, Weinblatt ME, et al. Pharmacokinetics of pegloticase and methotrexate polygluta-mate(s) in patients with uncontrolled gout receiving pegloticase and co-treatment with methotrex-ate. Ann Rheum Dis 2022; 81(suppl 1):910. doi:10.1136/annrheumdis-2022-eular.2757
Botson J, Saag K, Peterson J, et al. 12-month findings of the randomized, double-blind, placebo-controlled, multicenter, efficacy and safety study of methotrexate to Increase response rates in patients with uncontrolled gout receiving pegloticase (MIRROR RCT). [abstract 0001]. Arthritis Rheumatol 2022; 74(suppl 9):11. doi:10.1136/annrheumdis-2022-eular.568
Disclosures
John Botson: Horizon Therapeutics, AbbVie, Amgen, Allena Pharma, Radius Health, Aurinia Pharma-ceuticals, ChemoCentryx, Eli Lilly and Company, Novartis.