Botulinum toxin as an effective rescue treatment after failure of anti-CGRP monoclonal antibodies in chronic migraine patients

IF 2.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon Pub Date : 2025-10-01 DOI:10.1016/j.toxicon.2025.108605

Giovanni Ermanis , Yan Tereshko , Enrico Belgrado , Christian Lettieri , Gian Luigi Gigli , Mariarosaria Valente

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Abstract

anti-CGRP monoclonal antibodies (anti-CGRP mAbs) represent a highly effective prophylactic treatment for chronic migraineurs, but for some subjects they are ineffective. We aimed to determine if OnabotulinumtoxinA (BoNT/A) treatment may be helpful in these cases. We collected data from fourteen chronic migraineurs who attended our Headache Center and who did not benefit from anti-CGRP mAbs treatment. After anti-CGRP mAbs failure, these patients underwent at least one BoNT/A treatment according to the PREEMPT protocol. We then compared the variation in headache days (DOH), pain intensity (NRS), and symptomatic medication intake (ADI) before and after anti-CGRP mAbs therapy and before and after BoNT/A treatment: we confirmed that the interruption of anti-CGRP mAbs treatment had actually been due to a lack of benefit in terms of DOH (19.21 ± 7.58 days and 20.29 ± 8.32 days; p = 0.74), NRS (7.64 ± 0.75 vs 7.57 ± 1.01; p = 0.85) and ADI (42.86 ± 52.74 vs 45.64 ± 52.82; p = 0.79). All patients started BoNT/A therapy after discontinuing anti-CGRP mAbs. After a period without treatment, therapy with BoNT/A caused a significant reduction in DOH (23.86 ± 6.97 vs. 11.36 ± 10.10, p = 0.010), ADI (47.07 ± 51.19 vs. 20.50 ± 21.42, p = 0.010) and NRS (8.07 ± 1.00 vs. 6.64 ± 1.60, p = 0.014), improving clinical conditions in patients non-responders to anti-CGRP mAbs. It is not well established on which basis pharmacological resistance to anti-CGRP mAbs develops in such refractory patients. Still, these data may point towards a mechanism of pain relief that could not be solely related to CGRP pathways activity, thus being a good rescue therapy in resistant headache management, although further data are needed. Our preliminary results suggest that BoNT/A may be a promising salvage therapy option when anti-CGRP mAbs are ineffective, but evidence requires confirmation from basic research and in larger, uncontrolled, prospective studies in chronic migraineurs.

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肉毒杆菌毒素作为慢性偏头痛患者抗cgrp单克隆抗体失败后的有效抢救治疗

抗cgrp单克隆抗体（anti-CGRP mab）是一种非常有效的慢性偏头痛预防治疗方法，但对某些受试者无效。我们的目的是确定onabotulintoxina （BoNT/A）治疗是否对这些病例有帮助。我们收集了14例慢性偏头痛患者的数据，这些患者在我们的头痛中心就诊，并且没有从抗cgrp单克隆抗体治疗中获益。在抗cgrp单克隆抗体失败后，这些患者根据PREEMPT方案接受了至少一次BoNT/A治疗。然后我们头痛天(度)的变化相比,疼痛强度(NRS),和有症状的药物摄入量(ADI)之前和之后anti-CGRP马伯疗法和肉毒毒素/治疗:之前和之后我们确认中断anti-CGRP马伯治疗是由于缺乏效益的度(19.21±7.58天,20.29±8.32天;p = 0.74),评分量表(7.64±0.75 vs 7.57±1.01;p = 0.85)和ADI(42.86±52.74 vs 45.64±52.82;p = 0.79)。所有患者在停用抗cgrp单克隆抗体后开始BoNT/A治疗。在一段时间未治疗后，BoNT/ a治疗导致DOH（23.86±6.97比11.36±10.10,p = 0.010）、ADI（47.07±51.19比20.50±21.42,p = 0.010）和NRS（8.07±1.00比6.64±1.60,p = 0.014）显著降低，改善了抗cgrp单抗无反应患者的临床状况。这类难治性患者对抗cgrp单克隆抗体产生药理学耐药的基础尚不清楚。尽管还需要进一步的数据，但这些数据可能指向一种疼痛缓解机制，这种机制可能不仅仅与CGRP通路的活性有关，因此在难治性头痛管理中是一种很好的救援疗法。我们的初步结果表明，当抗cgrp单克隆抗体无效时，BoNT/A可能是一种有希望的挽救性治疗选择，但证据需要基础研究和更大规模的、无对照的、前瞻性的慢性偏头痛研究来证实。

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来源期刊

Toxicon 医学-毒理学

CiteScore

4.80

自引率

10.70%

发文量

358

审稿时长

68 days

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