Azathioprine May Increase Pegloticase Responsiveness in Chronic Refractory Gout

Companion treatment with azathioprine (AZA) is linked to increased responsiveness to pegloticase in chronic refractory gout, according to study results presented at the European League Against Rheumatism (EULAR) 2020 E-Congress, held online from June 3 to 6, 2020. AZA use increased the probably of long-term serum urate lowering with pegloticase.

This open-label, multicenter clinical trial enrolled patients with chronic gout who did not achieve serum urate levels <6 mg/dL with conventional urate-lowering therapy. Researchers tested levels of thiopurine methyl transferase, the enzyme which metabolizes AZA.

Patients with adequate levels of the enzyme were eligible for inclusion. Enrollees were started on daily oral AZA at 1.25 mg/kg for 1 week, then 2.5 mg/kg thereafter.

After 2 weeks of AZA exposure, patients were started on intravenous pegloticase 8 mg, administered biweekly for 24 weeks. The primary end point was persistent lowering of serum urate to <6 mg/dL over the 3 final study visits. Patients who experienced an increase of serum urate to >6 mg/dL did not receive additional pegloticase. Patients who experienced flares received the appropriate prophylaxis.

The study cohort included 12 patients to date, among whom 75% were white and 25% black. All patients were men. At baseline, mean age was 62.4±14.7 years; mean gout duration was 13.8±9.2 years. A total of 57.3% of patients had gout flares; 81.8% had hypertension; 45.5% had dyslipidemia; and 9.0% had coronary artery disease. Overall, 6 patients who completed the treatment course experienced persisted urate lowering.

As of June 2020, 2 patients remain on treatment and have also displayed persistent urate lowering. Two patients lost the urate lowering effect after 2 doses of pegloticase, following which they discontinued treatment. Two patients discontinued the study due to adverse events: 1 experienced an injection site reaction after pegloticase infusion and 1 displayed AZA intolerance. However, no AZA-specific adverse events were reported. Gout flares were observed in 6 patients, for a mean of 1.5 flares per patient.

These data suggest that AZA can be used safely to prevent loss of responsiveness to pegloticase in patients with chronic gout. AZA appeared to increase the frequency of long-term serum urate lowering in patients receiving pegloticase. Further study in a larger cohort is necessary to affirm these findings.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Rainey H, Baraf HSB, Yeo A, Lipsky P. Companion immunosuppression with azathioprine increases the frequency of persistent responsiveness to pegloticase in patients with chronic refractory gout. Presented at: EULAR 2020 E-Congress; June 3-6, 2020. Abstract THU0410.