PSS2 - Risk of Severe Adverse Reactions Related to Allopurinol and Febuxostat in Asians

Abstract

Allopurinol, an anti-hyperuricaemic agent, is one of the common causes of life-threatening cutaneous adverse reactions. Febuxostat is a newer urate-lowering drug. The safety of these two drugs remain unclear. This study aimed to compare the incidence and mortality associated with allopurinol or febuxostat related hypersensitivity in Asians. We conducted a cohort study and collected data of patients receiving allopurinol or febuxostat from the electronic medical records from January, 2012, through June, 2015, of the Chang Gung Memorial Hospital Health System in Taiwan. Among 51,505 and 10,034 patients receiving allopurinol and febuxostat prescriptions, 12,007 and 5,680 patients were identified as new users who had not previously exposed to these two drugs The incidence of hypersensitivity reactions, including maculopapular exanthema (MPE), drug reaction with eosinophilia and systemic symptom (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) related to allopurinol or febuxostat were analyzed. Proportion t-test performed, and P < .05 was considered statistically significant. There were 33 patients with allopurinol-induced hypersensitivity reactions (10 SJS/TEN, 8 DRESS, and 15 MPE) and only 1 case of febuxostat-induced MPE were indentified in this study. The overall incidence of hypersensitivity reactions induced by febuxostat was significantly lower than that induced by allopurinol (0.2 v.s. 2.7 per 1000 new users, P< 0.001). There were 4 deceased patients identified in patients with allopurinol-induced SJS/TEN but none in febuxostat users. Fourteen patients with allopurinol-induced hypersensitivity reactionsshifted to further febuxostat therapy were all well tolerant without any adverse reactions, even in patients with chronic kidney diseases or carried the risk HLA-B*58:01 allele. The incidence and severity of hypersensitivity reactions related to febuxostat are less than that of allopurinol in Asians. There was no risk of cross hypersensitivity between allopurinol and febuxostat of patients with allopurinol hypersensitivity.