Efficacy and Safety of Clobazam Adjunctive Therapy in Pediatric Patients with Drug-Resistant Epilepsy

Lingyan Yu,1,2,* Shunan Chen,1,3,* Zhou Zhang,4,* Yani Hu,1 Yuting Fang,5 Fengqian Mao,1,3 Suhong Wang,1,3 Zhenwei Yu,2,6 Xuejuan Li,4 Haibin Dai1– 3 1Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 2Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, 310058, People’s Republic of China; 3School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 4Shenzhen Children’s Hospital, Shenzhen, 518026, People’s Republic of China; 5First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, 230001, People’s Republic of China; 6Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haibin Dai, Email [email protected] Xuejuan Li, Email [email protected]: To determine the efficacy and safety of clobazam, a benzodiazepine derivative endorsed for adjunctive therapy in drug-resistant epilepsy due to its broad-spectrum efficacy and tolerability profile, as an adjunctive treatment for pediatric patients with drug-resistant epilepsy.Methods: This was a multicenter, real-world, self-controlled study. Pediatric drug-resistant epilepsy patients receiving clobazam adjunctive treatment at three centers were retrospectively included. The primary outcomes were response rates and seizure-free rates at 6 and 12 months of treatment. The secondary outcomes included retention rates at months 6 and 12 of treatment and adverse events that occurred during the addition of clobazam therapy.Results: A total of 146 patients were included. The retention rates were 87.67% (128/146) and 81.51% (119/146) at 6 and 12 months, respectively. The response rates were 58.99% (82/139) and 62.41% (83/133), and the seizure-free rates were 36.69% (51/139) and 35.34% (47/133) at 6 and 12 month, respectively. Clobazam has shown good efficacy in patients with epilepsy due to genetic variants (60.42%, 29/48) and its significantly better efficacy for the SCN1A genotype than for other genotypes (P=0.048). The independent factor associated with clinical response was a lower baseline seizure frequency (seizure frequency < 1 seizure/day). Adverse reactions occurred in 24 (24/146, 16.64%) patients, with excessive salivation/hypersalivation (4/146, 2.74%) and loss of appetite (4/146, 2.74%) being the most common.Conclusion: Clobazam adjunctive therapy is effective, safe and well tolerated in pediatric patients with drug-resistant epilepsy.Keywords: clobazam, drug-resistant epilepsy, adjunctive therapy, pediatric patient