Little Difference in eGFR With or Without Cotherapy with Methotrexate in Gout Treated with Pegloticase

John Botson, MD, RPh
Credit: Orthopedic Physicians Alaska

New data presented at the National Kidney Foundation (NKF) 2023 Spring Clinical Meeting is offering clinicians with insight into the effects of pegloticase with or without concomitant methotrexate on estimated glomerular filtration rate (eGFR).

An analysis of data from within the phase 3 MIRROR trial, results of the study demonstrate eGFR remained stable in a majority of patients treated with pegloticase, both with and without cotherapy with methotrexate, among all patients with an eGFR of 40 or greater.

“These data suggest that renal function was not negatively impacted during up to 52 weeks of pegloticase plus methotrexate co-therapy in uncontrolled gout patients,” wrote investigators. “Further study is needed to better understand the long-term effects of sustained urate-lowering on eGFR, particularly in patients with and without gout and advanced [chronic kidney disease].”

With initial approval from the US Food and Drug Administration in 2010, pegloticase (Krystexxa) offered patients with gout a new potential treatment option with proven ability to reduce uric acid in this patient population.² In 2022, the FDA approved an expanded indication for the agent, with approval for uncontrolled gout. This most recent approval was based on data from the phase 3 MIRROR trial, which examined use of pegloticase with methotrexate for treatment of chronic gout refractory to conventional therapies.³

A multicenter, open-label, efficacy and safety study, the MIRROR trial enrolled 152 patients. For inclusion in the trial, patients needed to be at least 18 years of age, be less than 352 pounds at screening, and have an eGFR greater than 40 ml/min/1.73 m2. Of note, women of childbearing potential were required to have negative serum/urine pregnancy tests during Screening and Week 6 while men who were not vasectomized had to agree to use appropriate contraception during the study.¹

The primary outcome of interest for the study was the percentage of serum uric acid responders during month 6. The trial included a secondary outcome of interest, which was defined as the percentage of serum uric acid responders during month 12.¹

Results of the trial suggested 71% of patients randomized to pegloticase with methotrexate compared to 40% of those randomized to pegloticase with placebo. Investigators of the trial pointed out there were no new safety concerns identified during the trial.⁴

In the current study, which was presented at NKF 2023 Spring Clinical Meeting, investigators sought to develop a more comprehensive understanding of the effects of the agent on kidney function, with and without methotrexate. To do so, investigators designed the study as an analysis of eGFR changes during pegloticase treatment up to 12 months within the trial.¹

From the trial, investigators identified 100 patients randomized to pegloticase plus methotrexate and 52 who were randomized to pegloticase plus placebo therapy. Per trial protocol, after a 2-week open-label methotrexate tolerability period and a 4-week blinded methotrexate and placebo run-in, patients began receiving pegloticase plus methotrexate or placebo.¹

Initial analysis of data from MIRROR indicated the mean eGFR was 69.8±17.5 ml/min/1.73 m2 in the methotrexate arm, which is a 4.6±1.5 ml/min/1.73 m2 change from baseline, and 69.7±22.5 ml/min/1.73 m2 in the placebo arm, which is a 1.7±2.7 ml/min/1.73 m2 change from baseline.¹

When assessing changes in eGFR classification, results indicated eGFR remained stable through the run-in and treatment periods in patients with baseline eGFR less than 60 ml/min/1.73 m2 in both treatment groups. Additional analysis indicated CKD stage was unchanged or had improved in the majority of patients.¹

References:

1. Marder B, Abdellatif A, Botson J. 230 EGFR changes during pegloticase treatment with and without methotrexate co-therapy: 12-month findings of Mirror RCT. American Journal of Kidney Diseases. 2023;81(4). doi:10.1053/j.ajkd.2023.01.232
2. Drug approval package. Krystexxa (Pegloticase) Injection. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125293s0000TOC.cfm. Accessed April 12, 2023.
3. FDA approves KRYSTEXXA® (pegloticase) injection co-administered with methotrexate, expanding the labeling to help more people with uncontrolled gout achieve a complete response to therapy. Horizon Therapeutics plc. https://ir.horizontherapeutics.com/news-releases/news-release-details/fda-approves-krystexxar-pegloticase-injection-co-administered. Published July 8, 2022. Accessed April 12, 2023.
4. Mirror randomized controlled trial meets primary endpoint and shows 71% of patients achieved a complete response rate using KRYSTEXXA® (Pegloticase Injection) with Methotrexate. Horizon Therapeutics plc. https://ir.horizontherapeutics.com/news-releases/news-release-details/mirror-randomized-controlled-trial-meets-primary-endpoint-and. Published October 25, 2021. Accessed April 12, 2023.