Pegloticase Plus Methotrexate Co-Therapy did not Impact Renal Function in Gout

Although pegloticase (KRYSTEXXA) can be highly effective in reducing urate burden in patients with refractory or uncontrolled gout, the risk of infusion reactions is high. Further, chronic kidney disease (CKD) is common patients with gout and methotrexate (MTX) is used with caution in this patient population. In the MIRROR RCT trial, investigators evaluated the impact of pegloticase plus MTX co-therapy on renal function in this patient population via changes in estimated glomerular filtration rate (eGFR) during the trial period. Results indicated that eGFR did not decrease after initiating MTX as co-therapy, suggesting the combination did not negatively impact renal function in this patient population.

Abdul Abdellatif, MD

After a brief run-in period, patients with uncontrolled gout were randomized to receive either pegloticase (biweekly 8mg infusion) plus oral MTX (15mg/week) co-therapy or pegloticase plus placebo co-therapy. Investigators measured eGFR at baseline prior to MTX exposure and any changes were reported and evaluated. Mean eGFR was stable during the run-in period across treatment arms. At month 6, a subgroup analysis based on pre-therapy eGFR showed that eGFR was comparable between both eGFR <60 and ≥60 groups.

Rheumatology Network interviewed co-investigator, Abdul Abdellatif, MD, FASN, to discuss the trial in more detail. Abdellatif is an adjunct assistant professor at Baylor College of Medicine Nephrology Division and the Kidney Hypertension Transplant Clinic of Clearlake Specialties.

Rheumatology Network: What first sparked your team's interest in analyzing pegloticase and methotrexate combination therapy in terms of kidney function?

Abdul Abdellatif, MD, FASN: Nine to 10 million adults in the United States are diagnosed with gout and 1 in 4 patients with moderate to severe chronic kidney disease is impacted by gout. This means in our patients with advanced kidney disease, gout is 8 to 10 times greater than the general population. The nephrologist in general is not as familiar with methotrexate as much as rheumatologists are. So, we wanted to test the efficacy and safety of using methotrexate for the treatment of gout, but we also wanted to study it in patients with kidney disease, looking for any potential benefit or side effect.

RN: In your opinion, what is the clinical significance of these results?

AA: Treating patients with pegloticase gave us more opportunity to treat patients better. In the pivotal trials, when we tested pegloticase, we had approximately 42% of patients with what we call complete response. However, when we combine it with methotrexate, we were able to get 70% of these patients to respond to the drug with less infusion reaction. The other factor we should note is that we did not see signs of kidney injury from methotrexate, bone marrow, liver injury, or muscle injury, meaning the drug was considered safe.

RN: What are the next steps for your team?

AA: This disease is unfortunately underdiagnosed, undertreated, and a lot of patients suffer from this condition and may be not on the appropriate therapies. Having the opportunity to control a disease with pegloticase is a breakthrough for my patients, but using it with methotrexate gives me even more confidence, allowing the patient to have a better chance of responding to treatment. When you add methotrexate, you improve the patient response to the medication, and you also decrease the risk for infusion reactions with or no significant negative change in kidney function.