García-Castillo María Clara, Sierra-Mencía Álvaro, Caronna Edoardo, Toledo-Alfocea Daniel, Jaimes Alex, Urtiaga Saray, Casas-Limón Javier, Muñoz-Vendrell Albert, Santos-Lasaosa Sonia, García Martín Valvanuz, Martín Ávila Guillermo, Polanco Marcos, Villar-Martínez Maria Dolores, Trevino-Peinado Cristina, Rubio-Flores Laura, Sánchez-Soblechero Antonio, Portocarrero Sánchez Leonardo, Luque-Buzo Elisa, Lozano-Ros Alberto, Gago-Veiga Ana Beatriz, Díaz-De-Terán Javier, Recio García Andrea, Canales Rodríguez Javiera, Gómez García Andrea, González Salaices Marta, Campoy Sergio, Mínguez-Olaondo Ane, Maniataki Stefania, González-Quintanilla Vicente, Porta-Etessam Jesús, Cuadrado María-Luz, Guerrero Peral Ángel Luis, Pozo-Rosich Patricia, Rodríguez-Vico Jaime, Huerta-Villanueva Mariano, Pascual Julio, Goadsby Peter J, Gonzalez-Martinez Alicia
Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Hospital Universitario de la Princesa, Madrid, Spain.
J Neurol. 2025 Jun 3;272(6):443. doi: 10.1007/s00415-025-13177-y.
Preclinical evidence supports the immunoregulatory role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology. The increasing use of anti-CGRP therapies in patients with migraine and other comorbidities raises the question whether the potential use of anti-CGRP monoclonal antibodies (CGRP-mAbs) therapies in combination with other immunological therapies is effective and safe.
This multicenter study included patients with migraine receiving CGRP-mAbs combined with immunosuppressive and immunomodulatory treatments. Clinical and demographic data, treatment history, laboratory markers and treatment-emergent adverse events (TEAEs) were analyzed. Effectiveness outcomes included the change in monthly migraine days (MMD) and monthly headache days (MHD) at 3, 6, 9 and 12 months, alongside the > 50% response rate. Moreover, autoimmune disease progression was also evaluated. We explored differences between patients with and without autoimmune disease activation.
Among 89 patients, there were 80 (90%) females with a mean age of 50 years (SD: 11), who had a high prevalence of psychiatric comorbidities (anxiety 44%, depression 49%) and medication overuse (68%). Patients receiving immunological treatments experienced significant reductions in MMD and MHD, with MMD decreasing from 16 (SD: 7) at baseline to 9 (SD: 8) at 6 months, and MHD dropping from 23 (SD: 8) to 17 (SD: 11). A 50% response in MMD was achieved by 46% at 6 months. TEAEs were reported in 28%, most commonly constipation (16%) and dizziness (9%).
CGRP-mAbs therapies combined with immunological treatments appear effective and safe in patients with autoimmune diseases. Larger prospective studies are necessary to confirm these findings and optimize management strategies.
临床前证据支持降钙素基因相关肽（CGRP）在偏头痛病理生理学中的免疫调节作用。偏头痛及其他合并症患者中抗CGRP疗法的使用日益增加，这引发了一个问题，即抗CGRP单克隆抗体（CGRP - mAbs）疗法与其他免疫疗法联合使用是否有效且安全。
这项多中心研究纳入了接受CGRP - mAbs联合免疫抑制和免疫调节治疗的偏头痛患者。分析了临床和人口统计学数据、治疗史、实验室指标以及治疗中出现的不良事件（TEAE）。有效性指标包括3、6、9和12个月时每月偏头痛天数（MMD）和每月头痛天数（MHD）的变化，以及>50%的缓解率。此外，还评估了自身免疫性疾病的进展情况。我们探讨了自身免疫性疾病激活患者与未激活患者之间的差异。
89例患者中，有80例（90%）为女性，平均年龄50岁（标准差：11），精神合并症（焦虑44%，抑郁49%）和药物过度使用（68%）的患病率较高。接受免疫治疗的患者MMD和MHD显著降低，MMD从基线时的16天（标准差：7）降至6个月时的9天（标准差：8），MHD从23天（标准差：8）降至17天（标准差：11）。6个月时，46%的患者MMD有50%的缓解。28%的患者报告了TEAE，最常见的是便秘（16%）和头晕（9%）。
CGRP - mAbs疗法与免疫治疗联合使用对自身免疫性疾病患者似乎有效且安全。需要更大规模的前瞻性研究来证实这些发现并优化管理策略。
