Incidence of Antiseizure Medication–Induced Severe Cutaneous Adverse Reactions in Malaysia

Abstract

Antiseizure medication can potentially cause severe cutaneous adverse reactions, and certain antiseizure medication‐induced severe cutaneous adverse reactions are associated with specific human leukocyte antigen alleles. This caused a change in antiseizure medication prescribing patterns, which may influence the incidence of antiseizure medication‐induced severe cutaneous adverse reactions. Thus, we aimed to determine the incidence of antiseizure medication‐induced severe cutaneous adverse reactions and its change over 15 years (2006‐2019) in Malaysia. This retrospective analysis combined antiseizure medication‐induced SCAR cases from the national adverse drug reaction database in the National Pharmaceutical Regulatory Agency, antiseizure medication usage data from the Malaysian Statistics of Medicine, and prescribing data from University Malaya Medical Centre, a national‐level tertiary hospital to calculate antiseizure medication‐induced SCAR incidence in Malaysia. We observed an upward trend in reported antiseizure medication‐induced SCAR cases from 28 cases in 2006 to 92 in 2016. The incidence of carbamazepine (CBZ)‐induced severe cutaneous adverse reactions increased from 7.5 per 1000 person‐years (2006) to 17.8 per 1000 person‐years (2016) but dropped to 7.2 per 1000 person‐years subsequently (2019). Concurrently, there was an increase in the incidence of severe cutaneous adverse reactions secondary to phenytoin and lamotrigine. The prevalent users of CBZ had reduced from 22.8% (2006) to 14.1% (2016), whereas the levetiracetam and sodium valproate users increased by 5.5% and 4.8%, respectively. The incidence of CBZ‐induced severe cutaneous adverse reactions had reduced since 2016, probably related to the implementation of human leukocyte antigen‐B*1502 screening in Malaysia or substitution of CBZ with other antiseizure medications. However, this was accompanied by an increase in SCAR incidence related to phenytoin and lamotrigine.

Integrating real‐world data in cost‐effectiveness analysis of universal HLA‐B*15:02 screening in Malaysia

“…However, this change did not reduce the overall ASM‐induced SCAR burden in Malaysia. On the contrary, we observed a worrisome upward trend of CBZ‐induced SCAR incidence over the years, from 0.75% in 2006 to 1.29% in 2018 (average incidence of 1.1%) 18 . Following the compelling success of HLA‐B*15:02 screening in an academic institute in reducing the CBZ‐induced SJS/TEN significantly (unpublished data), there is an apparent need to revisit the cost‐effectiveness of universal HLA‐B*15:02 screening prior to CBZ use with the latest RWE and a more realistic economic model reflecting the real‐world practice.…”

“…The current practice was modelled to reflect the change in ASM prescribing patterns owing to the increased awareness among clinicians on the association between HLA‐B*15:02 and CBZ‐induced SJS/TEN, however no routine HLA‐B*15:02 screening prior CBZ initiation was available in practice nationwide. Based on the published national prevalent ASM users in 2016, 18 the relative percentages of the 3 real‐world ASM prescriptions are 60% CBZ, 27% LEV and 13% LTG.…”

“…A threshold analysis was performed to determine the critical value of the proportion of patients prescribed with CBZ in current practice, which drove the base‐case findings to the opposite direction. In addition, sensitivity analyses to examine the impact of uncertainty on the incidence of SJS/TEN using a national estimate 18 and the utility of recurrent SJS/TEN were undertaken.…”

Carbamazepine‐Induced Severe Cutaneous Adverse Drug Reactions: A 21‐Year Comparison Between Children and Adults in Malaysia

“…Carbamazepine was also the most common AED causing SCARs in Hong Kong and Taiwan until the national implementation of HLA-B*15:02 screening policy, which significantly reduced the cases of carbamazepine-induced SCARs reported. 23,24 In a paper calculating incidence rate for carbamazepineinduced SCARs in Malaysia, Fong et al 25 showed that there was a downward trend in carbamazepine-induced SCAR incidence from 2017 to 2019. The trend could be due to the HLA-B*15:02 screening or substitution of carbamazepine with other antiseizure medications whenever the screening is not accessible, as HLA-B*15:02 testing has been available only in selected facilities in the capital, Kuala Lumpur, since 2013.…”

“…Although there are several drawbacks of a spontaneous reporting system such as underreporting and the lack of a denominator, the cases identified were sufficient to trigger a quantitative signal in our local and international ADR database for carbamazepine‐induced SCARs. In a previous study conducted by Fong et al, 25 using SCAR data from our database and national drug use data, the incidence rate for carbamazepine‐induced SCARs was calculated as an average of 11 per 1000 person‐years. In addition, this analysis was carried out on the basis of voluntary reports without intervention.…”