日本人小児部分てんかんに対するレベチラセタム長期継続併用療法—多施設共同非盲検試験

Effects of Long-Term Treatment with Levetiracetam as an Adjunctive Therapy in Japanese Children with Uncontrolled Partial-Onset Seizures: A Multicenter, Open-Label Study

既存の抗てんかん薬で発作が抑制されない日本人小児部分てんかん患者に対する14週間のレベチラセタム（LEV）併用療法の効果を検討した先行期間（第1期）を完了し，長期継続投与期間（第2期）に移行した55例を対象とし，長期安全性と有効性を評価した。有害事象および副作用発現率はそれぞれ98.2%と27.3%で，2%以上に認められた副作用は傾眠のみであった。重篤な有害事象および死亡がそれぞれ8例と1例あったが，LEVによる副作用は嘔吐の1例のみであり，長期投与で問題となる副作用は認められなかった。部分発作回数減少率（中央値）および50%レスポンダー率はそれぞれ43.32%と41.8%で，第1期の効果を維持した。小児部分てんかん患者に対しLEVの長期安全性と有効性が確認された。

Abstract

Following the first period of the multicenter, open-label, single-armed N01223 trial, the second period of the N01223 trial was conducted to evaluate long-term safety, along with the efficacy of adjunctive levetiracetam treatment (individualized dose range, 20-60 mg/kg/day or 1,000-3,000 mg/day) in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). Of the 62 children who completed the first period, 55 children ［age: 10.4±3.4 years (mean±standard deviation)］ were elected to enter the second period for a maximum of 39 months. Twenty children were withdrawn during this second period. Frequencies of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 98.2% (54/55 cases) and 27.3% (15/55 cases), respectively. The most common TEAEs were nasopharyngitis (76.4%), influenza (36.4%) and pyrexia (25.5%). The only frequent ADR (＞2%) was somnolence (3.6%). Although serious TEAEs and death were reported in 8 cases and 1 case (drowning), respectively, a serious ADR was only reported in 1 case (vomiting). The median percentage reduction and 50% response rate for POS were 43.32% and 41.8%, respectively. One child showed a maximum seizure-free period of 163 days. In conclusion, levetiracetam demonstrated long-term safety and good tolerance with beneficial efficacy as an adjunctive therapy in Japanese children with uncontrolled POS.

(Received June 30, 2015; Accepted July 14, 2015: Published November 1, 2015)