Efficacy of the HLA-B58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency-A Prospective Study.

Background: Thus far, human leukocyte antigen (HLA)-B58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs).

Objective: To determine the usefulness of prospective screening for the HLA-B58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment.

Methods: We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B58:01 allele. Of these, 503 HLA-B58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively.

Results: Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029).

Conclusions: The present study demonstrated the clinical usefulness of the HLA-B58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.