Patient-identified most bothersome symptom in preventive migraine treatment with eptinezumab: A novel patient-centered outcome.
Patient-identified most bothersome symptom in preventive migraine treatment with eptinezumab: A novel patient-centered outcome.
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作者：
Lipton RB;Dodick DW;Ailani J;McGill L;Hirman J;Cady R
描述 3 期、多中心、随机、双盲、安慰剂对照、平行组 PROMISE-2 试验中使用的患者确定的最烦人症状 (PI-MBS) 测量的方法和含义，并评估该测量对评估治疗的预防性偏头痛益处的贡献。尽管摆脱 MBS 是急性偏头痛治疗试验的共同主要终点，但其在预防性偏头痛试验中的评估有限。 PROMISE-2 研究评估了独特的 PI-MBS 测量作为次要终点。这是对 PROMISE-2 研究数据的二次分析。患有慢性偏头痛 (CM) 的成人随机接受静脉注射 (IV) eptinezumab 100 mg、eptinezumab 300 mg 或安慰剂，在第 0 天和每 12 周给药一次。在筛选访视时，患者被要求口头描述与其 CM 相关的 MBS；问题格式是开放式的。在随后的就诊中，患者被要求对从研究开始到该时间点的 MBS 严重程度的总体变化进行评分，使用 7 点顺序量表，范围从“非常糟糕”(-3) 到“非常改善”(+3)。患者在同一次就诊期间使用相同的评分量表和回忆期完成了患者总体变化印象 (PGIC) 评估。对终点进行了描述性总结；使用 Pearson 和 Spearman 方法计算事后相关性，以评估 PGIC 和 PI-MBS 之间以及 PGIC 和平均每月偏头痛天数（MMD；PROMISE-2 中的主要疗效终点）之间的关系。总共有 1072 名患者接受了治疗（依替珠单抗 100 毫克，n = 356；依替珠单抗 300 毫克，n = 350；安慰剂，n = 366）并纳入分析。已确定 23 种独特的 MBS； ≥10名患者报告的症状包括光敏感性（18.7%）、恶心/呕吐（15.1%）、活动疼痛（13.7%）、疼痛（12.4%）、头痛（11.2%）、声音敏感性（7.3%）、搏动/搏动性疼痛（4.7%）、认知障碍（4.1%）、疲劳（2.4%）、情绪变化（1.5%）和嗅觉敏感性（0.9%）。首次给药后 4 周（第 4 周），100 mg (45%) 和 300 mg (57%) 的 PI-MBS 显着或非常显着改善的比率高于安慰剂 (29%)。第二次给药后 4 周（第 16 周），PI-MBS 显着或非常显着改善的比例分别增加至 58%、65% 和 36%。在每个时间点，PGIC 评级显着或非常显着改善的患者百分比与患者报告的 PI-MBS 改善的患者百分比相似。患者对 PI-MBS 和 PGIC 变化的评分在不同时间点之间密切相关（Pearson，r 范围，0.83-0.88；Spearman，r 范围，0.83-0.89）；相关性的绝对值大于 MMD 和 PGIC 变化之间的相关性（Pearson，r 范围，-0.49 至 -0.52；Spearman，r 范围，-0.49 至 -0.52）。在 PROMISE-2 研究中的 CM 患者中，基线时报告了广泛的 PI-MBS。在整个研究过程中，与安慰剂接受者相比，接受 eptinezumab 治疗的患者报告其 PI-MBS 严重程度有更大改善，并且这种改善与 PGIC 研究结果密切相关。总的来说，这些结果表明 PI-MBS 是一种有前途且新颖的 CM 预防性试验结果测量方法，因此可以提供一种以患者为中心的独特方法，用于识别和测量对每个患者最重要的偏头痛症状的负担以及治疗的益处。
To describe the methodology and implications of the patient‐identified most bothersome symptom (PI‐MBS) measure used in the phase 3, multicenter, randomized, double‐blind, placebo‐controlled, and parallel‐group PROMISE‐2 trial and to evaluate the contribution of this measure to the assessment of the preventive migraine benefits of treatment. Although freedom from MBS is a coprimary endpoint in acute migraine treatment trials, its evaluation in preventive migraine trials is limited. The PROMISE‐2 study assessed a unique PI‐MBS measure as a secondary endpoint. This was a secondary analysis of data from the PROMISE‐2 study. Adults with chronic migraine (CM) were randomized to receive intravenous (IV) eptinezumab 100 mg, eptinezumab 300 mg, or placebo, administered on day 0 and every 12 weeks. At the screening visit, patients were asked to verbally describe the MBS associated with their CM; the question format was open ended. At subsequent visits, patients were asked to rate the overall change in severity of their MBS from study inception to that time point, using a 7‐point ordinal scale ranging from “very much worse” (−3) to “very much improved” (+3). Patients completed the Patient Global Impression of Change (PGIC) assessment during the same visits, using an identical rating scale and recall period. Endpoints were summarized descriptively; post hoc correlations using the methodologies of Pearson and Spearman were calculated to evaluate relationships between PGIC and PI‐MBS and between PGIC and mean monthly migraine days (MMDs; primary efficacy endpoint in PROMISE‐2). Altogether, 1072 patients received treatment (eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366) and were included in the analysis. There were 23 unique MBS identified; those reported by ≥10 patients included light sensitivity (18.7%), nausea/vomiting (15.1%), pain with activity (13.7%), pain (12.4%), headache (11.2%), sound sensitivity (7.3%), throbbing/pulsating pain (4.7%), cognitive disruption (4.1%), fatigue (2.4%), mood changes (1.5%), and sensitivity to smell (0.9%). Four weeks after the first dose (week 4), the rates of much or very much improvement in PI‐MBS were higher with eptinezumab 100 mg (45%) and 300 mg (57%) than with placebo (29%). Four weeks after the second dose (week 16), the proportions with much or very much improvement in PI‐MBS had increased to 58%, 65%, and 36%, respectively. At each time point, the percentages of patients with PGIC ratings of much or very much improved were similar to those for patient‐reported improvement in PI‐MBS. Patient ratings of changes in PI‐MBS and PGIC correlated strongly across time points (Pearson, r range, 0.83–0.88; Spearman, r range, 0.83–0.89); the absolute value of the correlations was greater than the correlation among changes in MMDs and PGIC (Pearson, r range, −0.49 to −0.52; Spearman, r range, −0.49 to −0.52). Among patients with CM in the PROMISE‐2 study, a broad range of PI‐MBS was reported at baseline. Throughout the study, patients treated with eptinezumab reported greater improvement in their PI‐MBS severity compared with placebo recipients, and this improvement correlated strongly with PGIC findings. Collectively, these results indicate that PI‐MBS is a promising and novel outcome measure for preventive trials of CM and thus may provide a unique patient‐centered approach for identifying and measuring the burden of migraine symptoms that matter most to each patient, as well as the benefits of treatment.
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影响因子：
7.4
作者：
Nir RR;Lee AJ;Huntington S;Noseda R;Bernstein CA;Fulton AB;Bertisch SM;Hovaguimian A;Buettner C;Borsook D;Burstein R
通讯作者：
Burstein R
影响因子：
7.4
作者：
Lampl, Christian;Thomas, Hallie;Steiner, Timothy J.
通讯作者：
Steiner, Timothy J.
DOI：
10.1016/b978-0-12-398270-4.00042-2
发表时间：
2015-01-01
期刊：
NEUROBIOLOGY OF BRAIN DISORDERS: BIOLOGICAL BASIS OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS
影响因子：
--
作者：
Borsook, David;Maleki, Nasim;Burstein, Rami
通讯作者：
Burstein, Rami
影响因子：
168.9
作者：
Reuter, Uwe;Goadsby, Peter J.;Klatt, Jan
通讯作者：
Klatt, Jan
影响因子：
4.9
作者：
Kelman, L;Tanis, D
通讯作者：
Tanis, D