HLA-B 15:21 carrier status is a susceptibility factor of carbamazepine-induced nonimmediate cutaneous adverse reactions in HLA-B 15:02-negative patients: A retrospective cohort study.

Risk HLA allele: carbamazepine presentation by HLA-B 15:21, accounting for residual cutaneous risk in patients negative for HLA-B 15:02.

Pre-prescription HLA-B 15:02 screening is standard practice to prevent carbamazepine-induced nonimmediate cutaneous adverse reactions (cADR) in Asian populations, but the residual risk after a negative screen remained poorly quantified. This single-centre retrospective Thai cohort reviewed 560 HLA-B 15:02-negative cases, 288 of whom actually received carbamazepine, with re-genotyping of the 15:11 and 15:21 alleles by quantitative PCR, Sanger sequencing and HLA typing. Carrier frequency for 15:11 or 15:21 was 6.9% (20/288) and 17 nonimmediate cADRs were confirmed, giving a residual risk of 0.059. cADRs occurred in 20.0% (4/20) of 15:11 or 15:21 carriers — all four cases carried 15:21 — versus 4.85% (13/268) of non-carriers, with an odds ratio of 5.84 (95% CI 1.58-19.07; p = 0.010) using Firth penalised logistic regression. The authors conclude that broader screening could further improve drug safety in populations with high HLA-B diversity.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value of this work is that it quantifies, in a real-world setting, what HLA-B 15:02 screening misses: close to 5% of cADRs persist in screen-negative patients. The 15:21 signal rests on only four events, hence a very wide confidence interval, in a single centre and without independent replication — not enough to broaden the screened allele panel today. The question remains relevant for Southeast Asian populations with high HLA diversity, where screening limited to 15:02 clearly leaves uncovered risk.

Analysis by Dr Thibaut Benquey