Abstract：
OBJECTIVE: To characterize the long-term (56-week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment.
BACKGROUND: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy.
METHODS: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24-week, randomized, double-blind, placebo-controlled phase and a 32-week open-label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double-blind phase (Weeks 21-24; any 12 consecutive weeks; Weeks 13-24) and the entire study (Weeks 53-56; any 12 consecutive weeks; any 4-week period). We assessed the long-term impact on mean monthly headache days and changes from baseline on the six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2.1).
RESULTS: We analyzed 1384 participants with chronic migraine (double-blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open-label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56-week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13-24 of the double-blind phase, significantly more onabotulinumtoxinA-treated (386/688 [56.1%]) than placebo-treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25-56, 81.1% (558/688) at Weeks 53-56, and 79.4% (546/688) during any consecutive 12-week period. Mean changes from baseline on the HIT-6 and MSQv2.1 questionnaire surpassed within-group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA-treated participants who achieved <15 monthly headache days during Weeks 21-24 had a greater mean HIT-6 score reduction (-6.5 vs. -1.4) and greater mean MSQv2.1 Role-Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period.
CONCLUSIONS: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache-related disability and migraine-specific quality of life compared with those who remained at or above the 15-monthly headache days threshold. Sustained benefits observed over 56 weeks support long-term onabotulinumtoxinA use for the prevention of CM.
BACKGROUND: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy.
METHODS: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24-week, randomized, double-blind, placebo-controlled phase and a 32-week open-label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double-blind phase (Weeks 21-24; any 12 consecutive weeks; Weeks 13-24) and the entire study (Weeks 53-56; any 12 consecutive weeks; any 4-week period). We assessed the long-term impact on mean monthly headache days and changes from baseline on the six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2.1).
RESULTS: We analyzed 1384 participants with chronic migraine (double-blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open-label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56-week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13-24 of the double-blind phase, significantly more onabotulinumtoxinA-treated (386/688 [56.1%]) than placebo-treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25-56, 81.1% (558/688) at Weeks 53-56, and 79.4% (546/688) during any consecutive 12-week period. Mean changes from baseline on the HIT-6 and MSQv2.1 questionnaire surpassed within-group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA-treated participants who achieved <15 monthly headache days during Weeks 21-24 had a greater mean HIT-6 score reduction (-6.5 vs. -1.4) and greater mean MSQv2.1 Role-Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period.
CONCLUSIONS: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache-related disability and migraine-specific quality of life compared with those who remained at or above the 15-monthly headache days threshold. Sustained benefits observed over 56 weeks support long-term onabotulinumtoxinA use for the prevention of CM.
摘要：
目的：研究慢性偏头痛（CM）患者在治疗后头痛天数/月减少至<15天/月时，持续的单曲霉素A治疗反应的长期（56周）益处。
背景：在经历CM的患者中，关于每月头痛天数减少至与发作性偏头痛一致的水平的数据有限。了解CM中持续预防性治疗反应的影响可以提供有关成功治疗影响的重要信息。
方法：两个3期研究评估偏头痛预防治疗成人中的onabotulinumtoxinA治疗试验包括24周，随机化，双盲,安慰剂对照阶段和32周开放标签阶段。合并数据以确定在双盲期(第21-24周;任何连续12周;第13-24周)和整个研究(第53-56周;任何连续12周;任何4周期间)的几个时间段期间在治疗期间具有<15天/月头痛的个体的比例。我们评估了六项头痛影响测试（HIT-6）和偏头痛特定生活质量问卷2.1版（MSQv2.1）对平均每月头痛天数和基线变化的长期影响。
结果：我们分析了1384名患有慢性偏头痛的参与者n=688；安慰剂，n=696；开放标签：n=688[单糖霉素A]）。在完成完整的56周治疗期之前，对onabotulinumtoxinA和安慰剂的停药率为25.4%（n=175）和29.3%（n=204），分别。在双盲阶段的第13-24周，与安慰剂治疗（342/696[49.1%]）相比，接受单苯磺胺毒素A治疗（386/688[56.1%]）的患者头痛天数<15天/月（p=0.010），与安慰剂反应者相比，onabotulinumtoxinA每月头痛天数更少。在第25-56周，使用onabotulinumtoxinA达到<15个月头痛日的参与者比例为60.9％（419/688），在第53-56周，为81.1％（558/688），在任何连续12周内为79.4％（546/688）周。HIT-6和MSQv2.1问卷相对于基线的平均变化在所有时期都超过了组内最小重要差异阈值。在第24周，在第21-24周期间达到<15个月头痛日的接受过奥溴霉素A治疗的参与者的平均HIT-6评分降低幅度更大（-6.5vs.-1.4)和更大的平均MSQv2.1角色-功能限制性得分改善(21.3vs.6.4）比同期未达到<15个月头痛日的人。
结论：与保持在或高于15个月头痛天数阈值的参与者相比，使用onabotulinumtoxinA治疗达到<15个月头痛天数的参与者在头痛相关残疾和偏头痛特异性生活质量方面取得了有意义的益处。在56周内观察到的持续益处支持长期使用抗菌药毒素A预防CM。
背景：在经历CM的患者中，关于每月头痛天数减少至与发作性偏头痛一致的水平的数据有限。了解CM中持续预防性治疗反应的影响可以提供有关成功治疗影响的重要信息。
方法：两个3期研究评估偏头痛预防治疗成人中的onabotulinumtoxinA治疗试验包括24周，随机化，双盲,安慰剂对照阶段和32周开放标签阶段。合并数据以确定在双盲期(第21-24周;任何连续12周;第13-24周)和整个研究(第53-56周;任何连续12周;任何4周期间)的几个时间段期间在治疗期间具有<15天/月头痛的个体的比例。我们评估了六项头痛影响测试（HIT-6）和偏头痛特定生活质量问卷2.1版（MSQv2.1）对平均每月头痛天数和基线变化的长期影响。
结果：我们分析了1384名患有慢性偏头痛的参与者n=688；安慰剂，n=696；开放标签：n=688[单糖霉素A]）。在完成完整的56周治疗期之前，对onabotulinumtoxinA和安慰剂的停药率为25.4%（n=175）和29.3%（n=204），分别。在双盲阶段的第13-24周，与安慰剂治疗（342/696[49.1%]）相比，接受单苯磺胺毒素A治疗（386/688[56.1%]）的患者头痛天数<15天/月（p=0.010），与安慰剂反应者相比，onabotulinumtoxinA每月头痛天数更少。在第25-56周，使用onabotulinumtoxinA达到<15个月头痛日的参与者比例为60.9％（419/688），在第53-56周，为81.1％（558/688），在任何连续12周内为79.4％（546/688）周。HIT-6和MSQv2.1问卷相对于基线的平均变化在所有时期都超过了组内最小重要差异阈值。在第24周，在第21-24周期间达到<15个月头痛日的接受过奥溴霉素A治疗的参与者的平均HIT-6评分降低幅度更大（-6.5vs.-1.4)和更大的平均MSQv2.1角色-功能限制性得分改善(21.3vs.6.4）比同期未达到<15个月头痛日的人。
结论：与保持在或高于15个月头痛天数阈值的参与者相比，使用onabotulinumtoxinA治疗达到<15个月头痛天数的参与者在头痛相关残疾和偏头痛特异性生活质量方面取得了有意义的益处。在56周内观察到的持续益处支持长期使用抗菌药毒素A预防CM。
