Department of Neurology, Mayo Clinic, Phoenix, AZ, USA.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Phoenix, AZ, USA.
Cephalalgia. 2023 Feb;43(2):3331024221144783. doi: 10.1177/03331024221144783.
The objective of this longitudinal study was to determine whether brain iron accumulation, measured using magnetic resonance imaging magnetic transverse relaxation rates (T2*), is associated with response to erenumab for the treatment of migraine.
Participants (n = 28) with migraine, diagnosed using international classification of headache disorders 3rd edition criteria, were eligible if they had six to 25 migraine days during a four-week headache diary run-in phase. Participants received two treatments with 140 mg erenumab, one immediately following the pre-treatment run-in phase and a second treatment four weeks later. T2* data were collected immediately following the pre-treatment phase, and at two weeks and eight weeks following the first erenumab treatment. Patients were classified as erenumab responders if their migraine-day frequency at five-to-eight weeks post-initial treatment was reduced by at least 50% compared to the pre-treatment run-in phase. A longitudinal Sandwich estimator approach was used to compare longitudinal group differences (responders vs non-responders) in T2* values, associated with iron accumulation. Group visit effects were calculated with a significance threshold of p = 0.005 and cluster forming threshold of 250 voxels. T2* values of 19 healthy controls were used for a reference. The average of each significant region was compared between groups and visits with Bonferroni corrections for multiple comparisons with significance defined as p < 0.05.
Pre- and post-treatment longitudinal imaging data were available from 28 participants with migraine for a total of 79 quantitative T2* images. Average subject age was 42 ± 13 years (25 female, three male). Of the 28 subjects studied, 53.6% were erenumab responders. Comparing longitudinal T2* between erenumab responders vs non-responders yielded two comparisons which survived the significance threshold of p < 0.05 after correction for multiple comparisons: the difference at eight weeks between the erenumab-responders and non-responders in the periaqueductal gray (mean ± standard error; responders 43 ± 1 ms vs non-responders 32.5 ± 1 ms, p = 0.002) and the anterior cingulate cortex (mean ± standard error; responders 50 ± 1 ms vs non-responders 40 ± 1 ms, p = 0.01).
Erenumab response is associated with higher T2* in the periaqueductal gray and anterior cingulate cortex, regions that participate in pain processing and modulation. T2* differences between erenumab responders vs non-responders, a measure of brain iron accumulation, are seen at eight weeks post-treatment. Less iron accumulation in the periaqueductal gray and anterior cingulate cortex might play a role in the therapeutic mechanisms of migraine reduction associated with erenumab.
本纵向研究旨在确定使用磁共振成像磁横向弛豫率（T2*）测量的脑铁积累是否与依瑞奈单抗治疗偏头痛的反应有关。
符合国际头痛疾病分类第 3 版标准诊断的偏头痛患者（n=28），如果在为期四周的头痛日记预治疗阶段有 6 至 25 天偏头痛发作，则有资格参加。参与者接受两次 140mg 依瑞奈单抗治疗，一次在预治疗阶段后立即进行，另一次在四周后进行。T2数据在预治疗阶段后立即采集，并在第一次依瑞奈单抗治疗后两周和八周采集。如果患者在初始治疗后五至八周的偏头痛天数与预治疗阶段相比减少了至少 50%，则将其分类为依瑞奈单抗应答者。使用纵向 Sandwich 估计器方法比较 T2值的纵向组间差异（应答者与无应答者），这些差异与铁积累有关。使用 Bonferroni 校正进行多重比较，组间效应计算的显著性阈值为 p=0.005，聚类形成阈值为 250 体素。使用 19 名健康对照者的 T2*值作为参考。比较两组和各次就诊之间每个显著区域的平均值，并对多重比较进行 Bonferroni 校正，将 p<0.05 定义为有统计学意义。
共有 28 名偏头痛患者提供了治疗前后的纵向影像学数据，共 79 张定量 T2图像。受试者的平均年龄为 42±13 岁（25 名女性，3 名男性）。在 28 名研究的受试者中，53.6%为依瑞奈单抗应答者。将依瑞奈单抗应答者与无应答者之间的纵向 T2进行比较，有两个比较在经过多重比较校正后的显著性阈值 p<0.05 后仍然存在：在依瑞奈单抗应答者和无应答者之间，在 8 周时，脑导水管周围灰质的差异（均值±标准误差；应答者 43±1ms 比无应答者 32.5±1ms，p=0.002）和前扣带回皮质的差异（均值±标准误差；应答者 50±1ms 比无应答者 40±1ms，p=0.01）。
依瑞奈单抗的反应与脑导水管周围灰质和前扣带回皮质的 T2升高有关，这些区域参与疼痛处理和调节。在治疗后 8 周，依瑞奈单抗应答者和无应答者之间的 T2差异（脑铁积累的测量值）可见。脑导水管周围灰质和前扣带回皮质的铁积累减少可能在依瑞奈单抗治疗偏头痛相关的治疗机制中发挥作用。
