(205) Role of Human Leukocyte Antigen in Anti-Epileptic Drugs Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Meta-Analysis

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1250

Presenting Author(s)

Girish Thunga
– Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Manipal, Karnataka, India

Co-Author(s)

Asha K. Rajan, PharmD
– Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education , CHENNAI, Tamil Nadu, India
Muhammed Rashid, MPharm, BPharm
– Research Scholar, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Manipal, Udupi, Karnataka, India
Manik Chhabra
– Manipal College of Pharmacuetical Sciences, Manipal Academy of Higher Education, Manipal, India
Viji Chandran
– Research scholar, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
Sreedharan Nair, MPharm, PhD, PhD
– Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India
Ananth Kashyap, PharmD
– Manipal College of Pharmacuetical Sciences, Manipal Academy of Higher Education, Manipal, Mysuru, Karnataka, India
Rajesh Venkataraman
– Professor & HOD, Sri Adichunchanagiri College of Pharmacy, Nagamangala, Karnataka, India

Background: Antiepileptic drugs (AEDs) are chronically used in the management of epilepsy and other co-morbidities associated with seizures. Severe cutaneous adverse drug reactions are strongly associated with adverse drug reactions of AEDs.

Objectives: We aimed to perform a systematic review and meta-analysis to identify, critically evaluate and synthesize the best possible evidence on HLA and its association with AED induced SJS/TEN in light of case-control studies.

Methods: Our study followed a PICOS framework for the inclusion of studies. MEDLINE/PubMed, Scopus, Embase, and the Cochrane Library were searched from inception to October 2021. A bibliographic search of selected articles and random searches of Google Scholar and Research Gate were also performed. Case-control studies on the association between HLA and any AEDs induced SJS/TEN were eligible for inclusion. The quality of included studies was assessed using the Quality of genetic studies (Q genie) tool.

Results: A total of 223 studies out of 1245 non-duplicate records were included in the systematic review, with 26 studies (6753 cases and 32,125 controls) included in the meta-analysis. The majority (n=7) of studies were from Thailand followed by China (n=5). CBZ (HLA-B, C, and DRB-1); LTG (HLA-A, B); PHY (A, B, C), and PB (A, C) had the significant association of increased risk with alleles. The funnel plot did not show any obvious asymmetry suggesting the absence of publication bias. All the studies were graded >46 with a mean score of 56 out of 77.

Conclusions: Our study showed a significant association between HLA alleles and AED-induced SJS/TEN. Further research is needed to confirm the exact role of genetic factors in the pathophysiology of severe cutaneous reactions.