Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
Eur J Neurol. 2022 Apr;29(4):1209-1217. doi: 10.1111/ene.15236. Epub 2022 Jan 21.
Erenumab (ERE) is the first anticalcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.
Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio-demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine-related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test-6), and use of abortive medications, during 3 months before and after ERE start were collected. Real-time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50-RESP) and 75% responder patients (75-RESP).
At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50-RESP, and 30/110 (27.3%) were 75-RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008-1.120], p = 0.024), number of failed preventive medications (0.753 [0.600-0.946], p = 0.015), and MIDAS score (1.011 [1.002-1.020], p = 0.017) were associated with 75-RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75-RESP (per G allele OR [95% CI]: 0.53 [0.29-0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28-1.10], p = 0.09]).
In this real-word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.
依瑞奈单抗（ERE）是首个获批用于偏头痛预防的抗降钙素基因相关肽受体单克隆抗体。部分患者对 ERE 反应不佳。
这是一项前瞻性多中心研究，纳入 110 例起始 ERE 70mg 每月 1 次治疗的偏头痛患者。收集患者基线时的社会人口学特征和偏头痛特征，包括平均每月偏头痛天数（MMD）、偏头痛相关负担（MIDAS[偏头痛残疾评估量表]和头痛影响测试-6），以及 ERE 治疗前 3 个月和治疗后使用的偏头痛急性治疗药物。采用实时聚合酶链反应检测降钙素受体样受体和受体活性修饰蛋白-1 基因的多态性变异。采用逻辑回归模型确定 50%应答患者（50-RESP）和 75%应答患者（75-RESP）的独立预测因素。
治疗 3 个月时，MMD 从 17.2 降至 9.2（p<0.0001），59/110（53.6%）例患者为 50-RESP，30/110（27.3%）例患者为 75-RESP。偏头痛发病年龄（比值比[OR] [95%置信区间（95%CI）]：1.062 [1.008-1.120]，p=0.024）、失败预防性药物数量（0.753 [0.600-0.946]，p=0.015）和 MIDAS 评分（1.011 [1.002-1.020]，p=0.017）与 75-RESP 相关。在所研究的遗传变异中，RAMP1 rs7590387 与较低的 75-RESP 可能性相关（每 G 等位基因 OR [95%CI]：0.53 [0.29-0.99]，p=0.048]），但该关联在调整混杂的临床变量后不再具有统计学意义（每 G 等位基因，0.55 [0.28-1.10]，p=0.09）。
在这项真实世界研究中，依瑞奈单抗治疗显著降低了 MMD。失败预防性药物数量、偏头痛负担和偏头痛发病年龄可预测依瑞奈单抗的反应。需要更大规模的研究来证实 RAMP1 rs7590387 作为依瑞奈单抗疗效遗传预测因子的可能作用。
