Israa Alfares1, Muhammad Shahid Javaid2, Zhibin Chen2, Alison Anderson2, Ana Antonic-Baker2, Patrick Kwan3,4. 1. Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia. 2. Department of Neuroscience, Central Clinical School, Monash University, Alfred Hospital, Melbourne, VIC, Australia. 3. Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia. patrick.kwan@monash.edu. 4. Department of Neuroscience, Central Clinical School, Monash University, Alfred Hospital, Melbourne, VIC, Australia. patrick.kwan@monash.edu.
Abstract
BACKGROUND: Cutaneous adverse drug reactions (cADRs) are one of the most common, severe, and life-threatening types of adverse reactions following treatment with antiseizure medications (ASMs). Some studies have reported a higher incidence of ASM-induced cADRs in females than in males. OBJECTIVE: This study sought to perform a systematic review, meta-analysis, and meta-regression to compare the ASM cADR risks between females and males. METHODS: We searched the literature using three databases (EMBASE, PubMed, and Web of Science) between October 1998 and November 2018, later updated to October 2019. Studies were included in the meta-analysis if they met the following criteria: (1) observational studies that estimated the incidence of cADRs related to ASMs; (2) provided the risk or odds ratio (OR) for cADRs among female and male patients exposed to ASMs; and (3) provided information on patients' characteristics. We assessed the impact of study characteristics, publication bias, and measures to reduce bias, and performed a DerSimonian and Laird random effects meta-analysis. RESULTS: We included 28 studies in this review. Of these, seven studies were eligible for inclusion in the meta-analysis, involving a total of 223,209 patients. Overall, females were more likely to develop cADRs to ASMs than males (OR 1.76, 95% confidence interval [CI] 1.55-1.99). The largest differences were observed in patients prescribed lamotrigine (OR 2.17, 95% CI 1.53-3.08, p < 0.001) and carbamazepine (OR 1.63, 95% CI 1.02-2.60, p = 0.042). Also, the OR trended higher for phenytoin (OR 2.46, 95% CI 0.79-7.65, p = 0.12), followed by oxcarbazepine (OR 1.91, 95% CI 0.75-4.85, p = 0.18) and sodium valproate (OR 0.60, 95% CI 0.12-2.99, p = 0.53), but the difference did not reach statistical significance. In the remaining 21 studies, 13 reported numerically higher risk of cADRs among females compared to male patients, and in five of these, the difference was statistically significant. CONCLUSION: Our findings confirmed that females are more susceptible to cADRs induced by ASMs than males. More research is needed to understand the pathophysiological mechanisms for this difference. PROTOCOL REGISTRATION: PROSPERO (CRD42018111943).
BACKGROUND: Cutaneous adverse drug reactions (cADRs) are one of the most common, severe, and life-threatening types of adverse reactions following treatment with antiseizure medications (ASMs). Some studies have reported a higher incidence of ASM-induced cADRs in females than in males. OBJECTIVE: This study sought to perform a systematic review, meta-analysis, and meta-regression to compare the ASM cADR risks between females and males. METHODS: We searched the literature using three databases (EMBASE, PubMed, and Web of Science) between October 1998 and November 2018, later updated to October 2019. Studies were included in the meta-analysis if they met the following criteria: (1) observational studies that estimated the incidence of cADRs related to ASMs; (2) provided the risk or odds ratio (OR) for cADRs among female and male patients exposed to ASMs; and (3) provided information on patients' characteristics. We assessed the impact of study characteristics, publication bias, and measures to reduce bias, and performed a DerSimonian and Laird random effects meta-analysis. RESULTS: We included 28 studies in this review. Of these, seven studies were eligible for inclusion in the meta-analysis, involving a total of 223,209 patients. Overall, females were more likely to develop cADRs to ASMs than males (OR 1.76, 95% confidence interval [CI] 1.55-1.99). The largest differences were observed in patients prescribed lamotrigine (OR 2.17, 95% CI 1.53-3.08, p < 0.001) and carbamazepine (OR 1.63, 95% CI 1.02-2.60, p = 0.042). Also, the OR trended higher for phenytoin (OR 2.46, 95% CI 0.79-7.65, p = 0.12), followed by oxcarbazepine (OR 1.91, 95% CI 0.75-4.85, p = 0.18) and sodium valproate (OR 0.60, 95% CI 0.12-2.99, p = 0.53), but the difference did not reach statistical significance. In the remaining 21 studies, 13 reported numerically higher risk of cADRs among females compared to male patients, and in five of these, the difference was statistically significant. CONCLUSION: Our findings confirmed that females are more susceptible to cADRs induced by ASMs than males. More research is needed to understand the pathophysiological mechanisms for this difference. PROTOCOL REGISTRATION: PROSPERO (CRD42018111943).
Authors: Noel Frey; Michael Bodmer; Andreas Bircher; Stephan Rüegg; Susan S Jick; Christoph R Meier; Julia Spoendlin Journal: Epilepsia Date: 2017-10-13 Impact factor: 5.864
Authors: Lawrence J Hirsch; David B Weintraub; Richard Buchsbaum; Hilary T Spencer; Tara Straka; Melissa Hager; Stanley R Resor Journal: Epilepsia Date: 2006-02 Impact factor: 5.864