【 文献重点摘要 】

Background

OnabotulinumtoxinA is approved for the prevention of headache in those with chronic migraine (CM); however, more clinical data on the risk-benefit profile for treatment beyond one year is desirable.

Methods

The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) Study is an international, multicenter, open-label long-term prospective study. Adults with CM received 155 U of onabotulinumtoxinA (31 sites in a fixed-site, fixed-dose paradigm across 7 head/neck muscles) every 12 weeks (±7 days) for 9 treatment cycles (108 weeks). The primary outcome was headache day reductions at 108 weeks; secondary outcomes were headache day reductions at 60 weeks and change in the 6-item Headache Impact Test (HIT-6) score. Safety and tolerability were assessed by reviewing the frequency and nature of adverse events (AEs). AEs were determined at each visit through patient self-report, general non-directed and, for specific AEs, directed questioning, and physical examination. Subgroup analyses for safety and efficacy included, but were not limited to, patients with/without concomitant oral preventive treatment and acute medication overuse at baseline.

Results

Enrolled patients (N=716) were 18–73 years old and most were female (n= 607, 84.8%). At baseline, patients reported an average 22.0 (SD = 4.8) headache days per month. 52.1% of patients (n= 373) completed the study. By 60 and 108 weeks, a significant reduction in headache days (− 9.2 days and − 10.7 days, respectively, P < 0.0001) was observed. Significant improvements (P < 0.0001) in HIT-6 scores (− 7.1 point change at week 108) were also demonstrated. 131 patients (18.3%) reported ≥1 treatment-emergent adverse events; most frequently reported was neck pain (n= 29, 4.1%). One patient reported a serious treatment-related adverse event (rash). No deaths were reported.

Conclusions

The COMPEL Study provides additional clinical evidence for the consistency of the efficacy and for the long-term safety and tolerability of onabotulinumtoxinA for the prevention of headache in those with CM who have been treated with onabotulinumtoxinA every 12 weeks over 2 years (9 treatments) with the fixed-site, fixed-dose injection paradigm.

Keywords

OnabotulinumtoxinA, Efficacy, Safety, Long-term, Chronic migraine, Prophylaxis

背景

OnabotulinumoxinA被批准用于预防慢性偏头痛(CM)患者的头痛；然而，需要更多关于超过一年的治疗风险-收益情况的临床数据。

方法

慢性偏头痛长效开放标签(COMPEL)研究是一项国际性、多中心、开放标签的长期前瞻性研究。成人CM患者每12周(±7天)接受155U的奥纳布林毒素A(31个部位，涉及7块头颈部肌肉)，共9个治疗周期(108周)。主要结果是108周时头痛天数减少；次要结果是60周时头痛天数减少和6项头痛影响测试(HIT-6)得分的变化。安全性和耐受性通过回顾不良事件(AEs)的频率和性质进行评估。在每次就诊时，通过患者自我报告、一般非直接检查，对于特定的AEs，通过直接提问和体检来确定AES。安全性和有效性的亚组分析包括，但不限于，基线时有/没有同时进行口服预防治疗和急性药物过度使用的患者。

结果

入选患者716例，年龄18~73岁，女性607例，占84.8%。在基线时，患者报告平均每月头痛天数为22.0天(SD=4.8)。52.1%的患者(n=373)完成了研究。治疗60wk和108wk时，头痛天数明显减少(−分别为9.2d和−10.7d，P<0.0001)。HIT-6评分(第108周−变化7.1分)也有明显改善(P<0.0001)。1 31名患者(18.3%)报告了≥-1治疗紧急不良事件；最常见的报告是颈部疼痛(n=29，4.1%)。一名患者报告了与治疗相关的严重不良事件(皮疹)。没有死亡报告。

结论

COMPE研究提供了更多的临床证据，证明了在固定部位、固定剂量注射模式下，每12周接受一次奥巴曲霉毒素A治疗的CM患者头痛的疗效的一致性和长期的安全性和耐受性。

关键词

奥纳博林毒素A，有效性，安全性，长期，慢性偏头痛，预防