CGRP-mediated trigeminovascular reactivity in migraine patients treated with erenumab

Lentsch, Simone de Vries; Al-Hassany, Linda; Ferrari, Michel; Terwindt, Gisela M.; MaassenVanDenBrink, Antoinette

doi:10.1136/jnnp-2021-327992

Cited by 14 publications

(15 citation statements)

References 5 publications

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“…The present study focused on identifying a possible early predictor for clinical response to treatment with erenumab. We deliberately chose to measure CGRP-LI early (after 2–4 weeks), as we did in another recent study from our group [ 17 ], so we could analyze the association with the clinical response, and at the same time rule out whether changes in CGRP-LI were a secondary effect due to a change in migraine days. Although CGRP-LI levels were not different between T0 and T1, an interaction was found with migraine reduction after three months.…”

Section: Discussionmentioning

confidence: 99%

“…Even though anti-CGRP (receptor) antibodies were specifically developed for the preventive treatment of migraine, it is yet unclear why some patients do not respond and others are responders. Recently, we demonstrated that CGRP-mediated trigeminovascular activity before initiating erenumab partly may explain this clinical response [ 17 ]. However, it is of utmost importance to increase the understanding of response to anti-CGRP treatment even further and to uncover reasons for (non-)response.…”

Section: Discussionmentioning

confidence: 99%

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Serum CGRP in migraine patients using erenumab as preventive treatment

et al. 2022

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Aim Serum levels of Calcitonin Gene-Related Peptide (CGRP)-like immunoreactivity (CGRP-LI) in migraine patients before and after starting treatment with erenumab were measured to evaluate the association with clinical treatment response. Methods Blood samples were collected from the cubital fossa before (T0) and 2–4 weeks after (T1) starting treatment with erenumab. Clinical response was monitored using a daily headache e-diary. Serum levels of CGRP-LI, assessed using radioimmunoassay, were compared between T0 and T1, correcting for migraine reduction. In addition, for both T0 and T1, linear regression models were constructed using migraine reduction as outcome and serum CGRP-LI as independent variable, corrected for age, gender and monthly migraine days (MMD) at baseline. Results Serum CGRP-LI did not differ between T0 and T1 (p = 0.30). However, there was an interaction between time and reduction in MMD (p = 0.01). Absolute reduction in MMD in the third month after treatment with erenumab was associated with serum CGRP-LI at T1, 2–4 weeks after starting treatment with erenumab (p = 0.003), but not with serum CGRP-LI at T0 (p = 0.24). Conclusion Lower serum CGRP-LI 2–4 weeks after starting treatment with erenumab was associated with a higher reduction in migraine days after three months of treatment. Although the underlying mechanisms remain to be determined, this suggests that changes in CGRP levels, shortly after starting erenumab, are important for its clinical effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum CGRP in migraine patients using erenumab as preventive treatment

et al. 2022

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“…While the visual hypersensitivity score in the present study did not decrease in patients with <50% MMD reduction in response to treatment with erenumab, in a different study we demonstrated that the CGRP-mediated trigeminovascular activity is inhibited in these <50% responders. 27 This suggests that the decrease in visual hypersensitivity is not directly related to trigeminal nerve blockage but may be a secondary effect of decrease in migraine days. This would fit the data that mAbs targeting CGRP are large molecules that cannot easily pass the blood-brain barrier, and most likely work via a peripheral site of action.…”

Section: Discussionmentioning

confidence: 99%

Visual hypersensitivity in patients treated with anti‐calcitonin gene–related peptide (receptor) monoclonal antibodies

et al. 2023

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Objective To evaluate the effect of treatment with anti‐calcitonin gene–related peptide (CGRP; receptor) antibodies on visual hypersensitivity in patients with migraine. Background Increased visual sensitivity can be present both during and outside migraine attacks. CGRP has been demonstrated to play a key role in light‐aversive behavior. Methods In this prospective follow‐up study, patients treated for migraine with erenumab (n = 105) or fremanezumab (n = 100) in the Leiden Headache Center were invited to complete a questionnaire on visual sensitivity (the Leiden Visual Sensitivity Scale [L‐VISS]), pertaining to both their ictal and interictal state, before starting treatment (T0) and 3 months after treatment initiation (T1). Using a daily e‐diary, treatment effectiveness was assessed in weeks 9–12 compared to a 4‐week pre‐treatment baseline period. L‐VISS scores were compared between T0 and T1. Subsequently, the association between the reduction in L‐VISS scores and the reduction in monthly migraine days (MMD) was investigated. Results At 3 months, the visual hypersensitivity decreased, with a decrease in mean ± standard deviation (SD) ictal L‐VISS (from 20.1 ± 7.7 to 19.2 ± 8.1, p = 0.042) and a decrease in mean ± SD interictal L‐VISS (from 11.8 ± 6.6 to 11.1 ± 7.0, p = 0.050). We found a positive association between the reduction in MMD and the decrease in interictal L‐VISS (β = 0.2, p = 0.010) and the reduction in ictal L‐VISS (β = 0.3, p = 0.001). Conclusion A decrease in visual hypersensitivity in patients with migraine after treatment with anti‐CGRP (receptor) antibodies is positively associated with clinical response on migraine.

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“…Furthermore, work in mice demonstrated that treatment with small molecule CGRP antagonists led to worsening of cerebral ischemic outcomes (83). A handful of studies have evaluated the effect of erenumab in vivo and while one demonstrated that erenumab did not alter vasomotor reactivity or flow-mediated dilation in migraine patients without aura, another demonstrated that it did affect trigeminovascular reactivity (84,85). Further large in vivo studies are needed to determine in more detail how the vasculature of patients with migraine responds to these drugs.…”

Section: Migraine and Strokementioning

confidence: 99%

Neurological and psychiatric comorbidities of migraine: Concepts and future perspectives

et al. 2023

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Background This narrative review aims to discuss several common neurological and psychiatric disorders that show comorbidity with migraine. Not only can we gain pathophysiological insights by studying these disorders, comorbidities also have important implications for treating migraine patients in clinical practice. Methods A literature search on PubMed and Embase was conducted with the keywords “comorbidity”, “migraine disorders”, “migraine with aura”, “migraine without aura”, “depression”, “depressive disorders”, “epilepsy”, “stroke”, “patent foramen ovale”, “sleep wake disorders”, “restless legs syndrome”, “genetics”, “therapeutics”. Results Several common neurological and psychiatric disorders show comorbidity with migraine. Major depression and migraine show bidirectional causality and have shared genetic factors. Dysregulation of both hypothalamic and thalamic pathways have been implicated as a possibly cause. The increased risk of ischaemic stroke in migraine likely involves spreading depolarizations. Epilepsy is not only bidirectionally related to migraine, but is also co-occurring in monogenic migraine syndromes. Neuronal hyperexcitability is an important overlapping mechanism between these conditions. Hypothalamic dysfunction is suggested as the underlying mechanism for comorbidity between sleep disorders and migraine and might explain altered circadian timing in migraine. Conclusion These comorbid conditions in migraine with distinct pathophysiological mechanisms have important implications for best treatment choices and may provide clues for future approaches.

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CGRP-mediated trigeminovascular reactivity in migraine patients treated with erenumab

Cited by 14 publications

References 5 publications

Serum CGRP in migraine patients using erenumab as preventive treatment

Serum CGRP in migraine patients using erenumab as preventive treatment

Visual hypersensitivity in patients treated with anti‐calcitonin gene–related peptide (receptor) monoclonal antibodies

Neurological and psychiatric comorbidities of migraine: Concepts and future perspectives

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