Allopurinol Noninferior to Febuxostat in the Treatment of Gout

Allopurinol demonstrates noninferiority and comparable safety to febuxostat in the treatment of gout, according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021.

The current double-blind, multicenter, randomized, 72-week trial included patients with gout (serum urate [SU] ≥6.8 mg/dL). Patients were randomly assigned 1:1 to receive allopurinol or febuxostat. All study participants had hyperuricemia that persisted despite treatment with allopurinol, and at least one-thirds had chronic kidney disease (CKD) stage 3. The 3 phases of the trial were urate-lowering therapy (ULT) titration (weeks 0-24), a maintenance phase (weeks 25-48), and an observation phase with continued ULT (weeks 49-72).

Daily doses of allopurinol and febuxostat were 100 mg (max 800 mg) and 40 mg (max 120 mg, reduced to 80 mg), respectively. Anti-inflammatory prophylaxis was administered at the discretion of the site investigator.

Primary endpoint was the number of participants who experienced at least 1 flare in the observation phase, with noninferiority indicated by a less than 8% difference. Secondary endpoints included serious adverse events, the number achieving SU less than 6 mg/dL by the end of maintenance, and the tolerability and efficacy in CKD stage 3.

A total of 940 patients with gout were included in the study; 20% of participants withdrew before study completion. During the observation phase, 35% of patients receiving allopurinol compared with 42% of those receiving febuxostat had at least 1 flare (P <.001 for noninferiority). A total of 80% of participants achieved SU less than 6.0 mg/dL, with 92% achieving serum urate less than 6.8 mg/dL.

Serious adverse events did not differ between those with and without CKD.

Researchers concluded that “allopurinol, when dosed appropriately as part of a treat-to-target strategy, is noninferior to febuxostat in the treatment of gout.” They indicated that both therapies demonstrated efficacy, with “80% of patients achieving and maintaining SU goals after 1 year and more than 90% achieving SU [less than] 6.8 mg/dL.” Researchers also noted that “no evidence of increased cardiovascular toxicity with febuxostat compared [with] allopurinol.” Furthermore, researchers indicated that “the comparative efficacy and safety of these [2] agents extended to patients with CKD stage 3.”

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

Reference

O’Dell J, Neogi T, Pillinger M, et al. Urate lowering therapy in the treatment of gout: a multicenter, randomized, double-blind comparison of allopurinol and febuxostat using a treat-to-target strategy. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 1900.