Decline in renal function is associated with hyperuricemia and gout. Independent of chronic kidney disease (CKD) stage, pegloticase has been shown to lower uric acid in patients with CKD and uncontrolled gout. Data from recent trials and case data support use of an immunomodulator with pegloticase to limit formation of antidrug antibody, increase urate-lowering response rate, and decrease the risk of infusion reaction.
CKD may limit immunomodulator use. Patients with estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m2 were excluded from clinical trials of pegloticase plus immunomodulator (methotrexate [MTX]). However, according to Brad A. Marder, MD, and colleagues, gout is common in patients with CKD and use of pegloticase plus immunomodulator has been reported.
The researchers performed an analysis of case data to examine changes in eGFR during cotherapy with pegloticase + MTX in patients with and without CKD. Results were reported during a poster session at the American Society of Nephrology Kidney Week 2022 in a poster titled eGFR Changes in Uncontrolled Gout Patients Undergoing Pegloticase Plus Methotrexate Co-Therapy
The retrospective analysis included pooled deidentified case data of pegloticase + MTX cotherapy. Patients were labeled as CKD (defined as baseline eGFR <60 mL/min/1.73 m2) or non-CKD (baseline eGFR ≥60 mL/min/1.73 m2). Serum uric acid, eGFR, blood cell counts, and liver function tests were monitored. Patient characteristics, treatment parameters, response rate (≥12 infusions, preinfusion 12 serum uric acid <6 mg/dL), eGFR, and adverse events were assessed. Response analyses excluded patients with <12 infusions who remained on therapy at time of data collection.
The analysis included data on 42 patients with uncontrolled gout. Of those, 15 were in the CKD group (13 stage 3 and 2 stage 4) and 27 were categorized as non-CKD. The comorbidity profiles of the two groups were similar; more patients in the CKD group were female (33% vs 7%) and ≥65 years of age (60% vs 19%).
In both groups, MTX was initiated approximately 4 weeks prior to pegloticase; the patients with CKD had a lower dose (15 vs 19 mg/week). The pegloticase response rates were similar in both groups (CKD, 92% vs non-CKD, 86%). In patients without CKD, 44% had an increase in eGFR (mean increase, +4.2 mL/min/1.73 m2). In patients with CKD, 60% had an increase in eGFR (mean increase, +11.5 mL/min/1.73 m2).
A total of 13 patients in the CKD group had stability/improvement in CKD stage (87%, both stage 4 improved to stage 3a and two stage 3a improved to stage 3b). There were no new safety signals identified. Seven patients in the CKD group (47%) and 13 in the non-CKD group (48%) had one or more adverse events (most commonly gout flare, 47 % and 41%, respectively). Pancytopenia (n=1) and mild immune response (n=1) were reported in the non-CKD group.
“These limited data show similar pegloticase + MTX urate-lowering efficacy in CKD and non-CKD patients. Most CKD patients had renal stability/improvement during therapy, but further study is needed,” the researchers said.
Source: Marder BA, Albert JA, Broadwell A, Padnick-Silver L, LaMoreaux B. eGFR changes in uncontrolled gout patients undergoing pegloticase plus methotrexate co-therapy. SA-PO897. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2022; November 5, 2022; Orlando, Florida. Funding for this study was provided by Horizon Therapeutics.