Pegloticase, Methotrexate Co-Therapy Has Similar Safety, Efficacy for Uncontrolled Gout Regardless of CKD Status

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Results showed co-administration of methotrexate with pegloticase led to similar rates of urate-lowering response and adverse events in patients with and without CKD.

Despite tolerability and toxicity concerns when using methotrexate in patients with renal impairment, a recent study found its co-administration with pegloticase in patients with uncontrolled gout with and without chronic kidney disease (CKD) was associated with similar efficacy and safety profiles.1

The pooled case series leveraged real-world data from previous studies of patients with uncontrolled gout and found pegloticase and methotrexate co-therapy was associated with sustained urate-lowering response, manageable adverse events, and potential improvements in renal function, regardless of patients’ CKD status.1

The bidirectional relationship between gout and CKD often means patients are affected by both diseases. The prevalence of renal impairment in patients with gout suggests the need for additional consideration when prescribing medications, including adjusted dosing or overall avoidance, due to their potential negative impact on kidney function. Methotrexate, an immunomodulating disease-modifying anti-rheumatic drug (DMARD), has been shown to improve urate-lowering response rate when given with pegloticase, although there are concerns about its use in patients with gout and kidney disease.2,3

“Though randomized clinical trials examining pegloticase plus immunomodulation co-therapy included some patients with an eGFR between 40 and 60 mL/min/1.73 m2, data in patients with comorbid gout and advanced CKD is limited,” John Albert, MD, MBA, physician/partner at Rheumatic Disease Center, and colleagues.1

Investigators retrospectively examined de-identified real-world case data for patients who underwent pegloticase and methotrexate co-therapy and categorized them as CKD, defined as baseline estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, or non-CKD, defined as baseline eGFR ≥ 60 mL/min/1.73 m2. Patient characteristics, pegloticase treatment parameters, the proportion of treatment responders, renal function changes, and adverse events were examined and compared between groups.1

Investigators identified and retrospectively enrolled 42 patients with uncontrolled gout who were treated with pegloticase and methotrexate co-therapy. Among the cohort, the mean age was 59.3 years, 83.3% of patients were male, and 81.0% were Caucasian. On average, patients had a 15.2 ± 13.1 year gout history and a pre-therapy serum urate of 9.2 ± 1.9 mg/dL.1

Investigators classified 15 (35.7%) patients as having CKD and the remaining 27 (64.3%) as non-CKD. They noted patient characteristics and comorbidity profiles were similar between the groups but pointed out those with CKD were older (72.0 vs 52.3 years; P <.001) and more often female (33.3% vs 7.4%; P = .003).1

Timing of methotrexate initiation prior to the first pegloticase infusion was similar in both groups, although the mean overall methotrexate dose was significantly lower in CKD patients (14.8 vs 19.3 mg/week; P = .019). On average, the number of pegloticase infusions and duration of pegloticase treatment were also similar, as was the proportion of CKD and non-CKD patients who had a sustained urate-lowering response through at least infusion 12.1

Whereas eGFR did not significantly differ before and after therapy in the non-CKD group (84.1 vs 88.3 mL/min/1.73 m2; P = .177), post-therapy eGFR tended to be higher than pre-therapy values in the CKD group (43.2 vs 54.7 mL/min/1.73 m2; P = .052). Investigators noted eGFR increased during treatment in 60% of CKD and 44% of non-CKD patients.1

They also pointed out patients who had a decrease in eGFR during treatment tended to have a lower baseline renal function (62.0 vs 71.7 mL/min/1.73 m2) and longer gout duration (20.8 vs 13.1 years). Univariate linear regression showed the relationship between change in eGFR and baseline eGFR was not significant (R2 = .0047, P = .674), although the relationship between change in eGFR and gout duration was (R2 = .1253, P = .043).1

Investigators divided patients by gout duration and observed those with a disease duration > 11 years had a significantly lower eGFR change (+0.7 vs +14.5 mL/min/1.73 m2; P = .032) and were more likely to have a decrease in eGFR (46.7% vs 11.1%; Odds ratio, 7.00; 95% CI, 1.17–41.76; P = .033) during therapy than those with gout duration ≤11 years.1

Adverse events were similar between patients with and without baseline CKD, with ≥ 1 adverse event reported in 53.3% and 66.7% of patients, respectively. Gout flare was the most common adverse event in both groups.1

Investigators outlined several potential limitations to these findings, including the small study sample, lack of standardization for treatment duration and monitoring timepoints, and the potential for selection bias.1

Nonetheless, they concluded: “Overall study findings provide much needed insight into renal function changes during pegloticase and methotrexate co-therapy in uncontrolled gout patients with and without CKD.”


  1. Albert J, Broadwell A, Padnick-Silver L, et al. Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series. Medicine (Baltimore). 2024;103(10):e37424. doi:10.1097/MD.0000000000037424
  2. Children’s Hospital at Montefiore. Chronic Kidney Disease: Medicines to Be Careful With. October 11, 2023. Accessed March 22, 2024.
  3. Versus Arthritis. Methotrexate. Accessed March 22, 2024.