Background

This randomized phase 3 study with double-blind main period (MP) and open-label extension (OLEX; NCT02002884) assessed incobotulinumtoxinA safety and efficacy for pediatric upper-limb spasticity treatment in ambulant/nonambulant (Gross Motor Function Classification System [GMFCS] I-V) patients, with the option of combined upper- and lower-limb treatment.

Methods

Patients were aged two to 17 years with unilateral or bilateral spastic cerebral palsy (CP) and Ashworth Scale (AS) score ≥2 in treatment-selected clinical patterns. In the MP, patients were randomized (2:1:1) to incobotulinumtoxinA 8, 6, or 2 U/kg body weight (maximum 200, 150, 50 U/upper limb), with optional lower-limb injections in one of five topographical distributions (total body dose ≤16 to 20 U/kg, maximum 400 to 500 U, depending on body weight and GMFCS level). In the OLEX, patients received three further treatment cycles, at the highest MP doses (8 U/kg/upper limb group). Outcomes included AS, Global Impression of Change Scale (GICS), and adverse events (AEs).

Results

AS scores improved from baseline to week 4 in all MP dose groups (n = 350); patients in the incobotulinumtoxinA 8 U/kg group had significantly greater spasticity improvements versus the 2 U/kg group (least-squares mean [standard error] for upper-limb main clinical target pattern −1.15 [0.06] versus −0.93 [0.08]; P = 0.017). Investigator's, child/adolescent's, and parent/caregiver's GICS scores showed improvements in all groups. Treatment benefits were sustained over further treatment cycles. AE incidence did not increase with dose or repeated treatment across GMFCS levels.

Conclusions

Data provide evidence for sustained efficacy and safety of multipattern incobotulinumtoxinA treatment in children and adolescents with upper-limb spasticity.

中文翻译：

---

IncobotulinumtoxinA 对小儿脑瘫上肢痉挛的疗效/安全性：随机对照试验

背景

这项具有双盲主期 (MP) 和开放标签扩展 (OLEX; NCT02002884) 的随机 3 期研究评估了 incobotulinumtoxinA 在步行/非步行中治疗儿科上肢痉挛的安全性和有效性（大运动功能分类系统 [GMFCS] IV ) 患者，可选择上肢和下肢联合治疗。

方法

在治疗选择的临床模式中，患者年龄在 2 至 17 岁之间，患有单侧或双侧痉挛性脑瘫 (CP) 和 Ashworth 量表 (AS) 评分≥2。在 MP 中，患者被随机分配 (2:1:1) 接受 incobotulinumtoxinA 8、6 或 2 U/kg 体重（最大 200、150、50 U/上肢），可选的下肢注射在五种之一地形分布（全身剂量≤16 至 20 U/kg，最大 400 至 500 U，取决于体重和 GMFCS 水平）。在 OLEX 中，患者接受了三个进一步的治疗周期，以最高的 MP 剂量（8 U/kg/上肢组）。结果包括 AS、全球变化印象量表 (GICS) 和不良事件 (AE)。

结果

在所有 MP 剂量组（n = 350）中，AS 评分从基线到第 4 周都有所提高；与 2 U/kg 组相比，incobotulinumtoxinA 8 U/kg 组的患者痉挛改善显着更大（上肢主要临床目标模式的最小二乘平均值 [标准误差] -1.15 [0.06] 与 -0.93 [0.08]；P  = 0.017）。调查员、儿童/青少年和父母/看护人的 GICS 评分显示所有组都有改善。在进一步的治疗周期中，治疗益处得以持续。AE 发生率并未随着 GMFCS 水平的剂量或重复治疗而增加。

结论

数据为上肢痉挛的儿童和青少年多模式肉毒杆菌毒素A治疗的持续有效性和安全性提供了证据。