Associations of HLA genetic variants with carbamazepine-induced cutaneous adverse drug reactions: An updated meta-analysis.

Abstract

Aggregated risk of carbamazepine (CBZ)-induced cutaneous adverse drug reactions (cADRs) with different HLA variants are unclear and limited in terms of the power of studies. This study aimed to assess the aggregated risk of CBZ-induced cADRs associated with carrying the following HLA variants: HLA-B*15:02, HLA-B*15:11, HLA-B*15:21, HLA-B*38:02, HLA-B*40:01, HLA-B*46:01, HLA-B*58:01, HLA-A*24:02, and HLA-A*31:01. Literature was searched in different databases following PRISMA guidelines. The outcomes were measured as odds ratio (OR) using RevMan software by a random/fixed effects model, where p < 0.05 was set as statistical significance. In total, 46 case-control studies met the inclusion criteria and were included in this analysis consisting of 1817 cases and 6614 controls. It was found that case-patients who carried the HLA-B*15:02 allele were associated with a significantly increased risk of CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) compared to controls (OR 26.01; 95% CI 15.88-42.60; p < 0.00001). The aggregated risk of cADRs was slightly higher in Asian compared to Caucasian patients (Asians: OR 14.84; 95% CI 8.95-24.61; p < 0.00001; Caucasians: OR 11.65; 95% CI 1.68-80.70; p = 0.01). Further, HLA-B*15:11, HLA-B*15:21, or HLA-A*31:01 allele was also associated with significantly increased risk of CBZ-induced cADRs (HLA-B*15:11: OR 6.08; 95% CI 2.28-16.23; p = 0.0003; HLA-B*15:21: OR 5.37; 95% CI 2.02-14.28; p = 0.0008; HLA-A*31:01: OR 5.92; 95% CI 4.35-8.05; p < 0.00001). Other HLA variants were not found to have any significant associations with CBZ-induced cADRs. Strong associations between the HLA-B*15:02, HLA-B*15:11, HLA-B*15:21, or HLA-A*31:01 allele with CBZ-induced cADRs have been established in this analysis. Pharmacogenetic testing of particular HLA alleles before initiation of CBZ therapy may be beneficial to patients and may help to eradicate cADRs substantially.

• Authors: Mohitosh Biswas, Maliheh Ershadian, John Shobana, Ai-Hoc Nguyen, Chonlaphat Sukasem
• Journal: Clinical and translational science (Clin Transl Sci) Vol. 15 Issue 8 Pg. 1887-1905 (08 2022) ISSN: 1752-8062 [Electronic] United States
• PMID: 35599240 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Chemical References

• Anticonvulsants
• HLA-A Antigens
• HLA-B Antigens
• Benzodiazepines
• Carbamazepine

Topics

• Anticonvulsants (adverse effects)
• Benzodiazepines
• Carbamazepine (adverse effects)
• Genetic Predisposition to Disease
• Genotype
• HLA-A Antigens (genetics)
• HLA-B Antigens (genetics)
• Humans