A型ボツリヌス毒素製剤（Botulinum Toxin Type A）の脳卒中後の下肢痙縮に対する臨床評価―プラセボ対照二重盲検群間比較試験ならびにオープンラベル反復投与試験

Efficacy and Safety of Botulinum Toxin Type A in treating Lower Limb Spasticity in Post-stroke Patients : A Multicenter, Double-blind, Placebo-controlled Trial followed by an Open-label Trial

要旨　【目的】脳卒中後の下肢痙縮患者を対象にA型ボツリヌス毒素製剤（botulinum toxin type A：BTXA）単回投与時の有効性をプラセボを対照として検証し，反復投与した際の有効性および安全性を評価した．【方法】下肢痙縮患者120例にBTXA300単位またはプラセボを対象筋に1回筋注し，投与12週以降は再投与基準を満たした被験者にBTXA300単位を最大3回反復投与し，48週まで観察を行った．【結果】足関節のModified Ashworth Scale（MAS）の投与前からの変化量に基づく曲線下面積の平均値の差は，BTXA群とプラセボ群間で-3.428であり，BTXA群で有意な減少が認められた（p＝0.006，t検定）．反復投与によりMASは更なる改善を示した．副作用発現頻度はBTXA群，プラセボ群間で著明な差は認められず，反復投与において副作用発現率の増加は認められなかった．【結論】BTXAは初回投与から下肢痙縮を改善し，長期的に有効で安全な治療法に成り得ると考えられた．

Abstract　Objective : To evaluate the efficacy and safety of botulinum toxin type A (BTXA) in Japanese patients with post-stroke lower limb spasticity in a multicenter, randomized, double-blind, single dose, placebo-controlled study (double-blind phase) followed by an open-label, multiple dose extension (open-label phase). Methods : One hundred and twenty patients with lower limb spasticity were randomized to receive a single treatment with BTXA 300 Units (U) or placebo into lower limb muscles in the double-blind phase. Patients who met the re-injection criteria received up to 3 repeated treatments of BTXA into lower limb muscles with at least 12 weeks between treatments in the open-label phase through 48 weeks. Results : In the double-blind phase there was significant improvement from baseline spasticity in the Modified Ashworth Scale (MAS) ankle score between the BTXA 300U and placebo groups, with a mean difference in the area under the curve (AUC) of -3.428 (p＝0.006, t test). The MAS ankle score further decreased from baseline in all repeat treatment cycles of BTXA in the open-label phase. No clinically relevant difference was noted in the frequency of treatment-related adverse events between BTXA-treated and placebo-treated patients during the study period. Conclusions : BTXA reduced spasticity in lower limb muscles from the first treatment with continued long-term efficacy. BTXA is safe and effective for the long-term treatment of post-stroke lower limb spasticity.