Real-world study of Asian population: incidence of severe skin adverse reactions caused by anti-epileptic drugs

Research background and purpose Patients receiving anti-epileptic drug therapy often have skin-related adverse reactions.
Severe skin reactions (SCARs) are rare adverse reactions that can lead to multiple organ failure, prolong hospitalization, and increase the risk of death.
Few studies have reported the incidence of serious skin adverse reactions to antiepileptic drugs.

Therefore, this study evaluated the incidence of serious skin adverse reactions in seven commonly used antiepileptic drugs, including carbamazepine, phenytoin, oxcarbazepine, lamotrigine, zonisamide, levetiracetam, and topiramate.
And compare the related risks of different drugs.

Research method This study collected 7 kinds of first prescriptions of carbamazepine, phenytoin, oxcarbazepine, lamotrigine, zonisamide, levetiracetam and topiramate in the Korean medical insurance database from January 2012 to December 2018 All patient data of antiepileptic drugs are used for correlation analysis of the incidence of serious skin adverse reactions.

Among them, severe skin adverse reactions are defined as the appearance of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) in ICD-10 Any kind of.

 Results of the study The incidence of severe skin adverse reactions of different antiepileptic drugs were 302,104 patients respectively.
Topiramate had the lowest incidence of severe skin adverse reactions (400/1,000,000 person-years) and the highest incidence of severe skin adverse reactions of phenytoin (5750).
/1,000,000 person-years) (see Table 1).Table 1 The incidence of severe skin adverse reactions of different anti-epileptic drugs At the same time, in order to compare the difference in the incidence of severe skin adverse reactions of different anti-epileptic drugs, this study chose carbamazepine and levetiracetam as the benchmarks to conduct with other anti-epileptic drugs.
Comparison, the results show: ➤ The incidence of severe skin adverse reactions in patients treated with topiramate was significantly lower than that of carbamazepine (P<0.
05), and the incidence of severe skin adverse reactions in patients treated with phenytoin and lamotrigine was significantly higher than that of carbamazepine.
Carbamazepine (all P＜0.
05); ➤The incidence of severe skin adverse reactions in patients treated with topiramate was significantly lower than that of levetiracetam (P＜0.
05), and other antiepileptic drugs other than carbamazepine had serious adverse skin reactions The incidence was significantly higher than that of Levetiracetam (all P＜0.
05).

Risk factors related to severe skin adverse reactions of different antiepileptic drugs ➤Gender: Male epilepsy patients using zonisamide are significantly associated with an increased risk of severe skin adverse reactions, but do not include antiepileptic drugs such as topiramate and levetiracetam.

➤Common skin diseases: Comorbid skin diseases will significantly increase the incidence of serious skin adverse reactions related to the use of antiepileptic drugs such as carbamazepine, phenytoin, oxcarbazepine, lamotrigine or levetiracetam, but not Increase the risk of serious skin reactions when using topiramate.

➤Comorbid liver disease: Comorbid liver disease will significantly increase the risk of serious skin reactions to drugs such as carbamazepine or phenytoin, but will not increase the risk of serious skin reactions to antiepileptic drugs such as topiramate and levetiracetam .

➤Comorbid allergic diseases: Comorbid allergic diseases will not significantly increase the risk of serious skin adverse reactions caused by the use of topiramate and other 7 anti-epileptic drugs.

Discussion This study compared the incidence of severe skin adverse reactions to 7 antiepileptic drugs.
It is the largest database study in this field in Asia.

Compared with a large-scale database study in the United Kingdom, the results of this study show that the incidence of serious skin reactions is generally higher, which indicates that there are certain differences in the genetic susceptibility of antiepileptic drugs to the risk of serious skin reactions in different countries.

It is worth mentioning that the UK database study did not observe that topiramate and levetiracetam caused Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).
This study also showed that treatment with topiramate Of patients have the relatively lowest risk of serious skin adverse reactions.

Topiramate is a new type of non-aromatic anti-epileptic drug, and the risk of serious adverse skin reactions is relatively low.

In addition, comorbid diseases and concomitant medications can also affect the risk of serious adverse skin reactions.

In addition to patients receiving topiramate treatment, patients with skin diseases are more likely to have serious adverse skin reactions.
For patients with skin diseases, topiramate is a better medication choice.

Literature index: Chung SJ, Ahn K ,Ji HO, et al.
Incidence rates of severe cutaneous adverse reactions due to antiseizure medication: A nationwide study using health claims data inKorea[J].
Epilepsia, 2020.