Effectiveness and Safety of CGRP-mAbs in Menstrual-Related Migraine: A Real-World Experience

DOI: https://doi.org/10.1007/s40122-021-00273-w

Abstract-Summary Evidence strongly suggests that estrogen fluctuations are involved in migraine attacks worsening during the perimenstrual window through several mechanisms directly or indirectly involving the CGRP pathway.

We aimed to evaluate whether mAbs blocking CGRP-ligand or receptor (CGRP- mAbs) could represent an effective and safe preventive treatment for menstrual migraine attacks in patients with menstrual-related migraine (MRM) with previous treatment failures.

At the baseline and after six CGRP-mAbs administrations, patients underwent to extensive interviews to assess frequency, duration, intensity, and responsiveness to painkiller intake of migraine attacks occurring during the perimenstrual window.

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After six administrations of CGRP-mAbs we observed a reduction of median menstrual migraine frequency (from 5 to 2 days per month), pain intensity (from 8/10 to 6/10), and attacks duration (from 24 to 8 h) (p < 0.001).

CGRP-mAbs could represent a safe and effective preventive therapeutic strategy able to reduce the disabling burden of menstrual migraine attack frequency, dura- tion, intensity, and significantly improve the response to painkillers.

These findings could be related to and further indirectly prove the greater influ- ence of CGRP-mediated mechanisms in the pathophysiology of menstrual migraine attacks.

Extended: Further studies with a larger sample size and a longer period of obser- vation are needed to better clarify these preliminary findings as well as to demon- strate the effectiveness and safety of mAbs CGRP also in PMM patients.

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Introduction Data emerging from both randomized controlled trials and real-life experiences strongly supported CGRP-mAbs efficacy and tolerability as preventive treatments for both episodic and chronic migraine [4, 208–210].

To the best of our knowledge, no real-life experiences have specifically demon- strated the efficacy and safety of CGRP-mAbs to treat migraine attacks occurring during the perimenstrual window.

We report the data emerging from our real-life experience using the CGRP-mAbs in patients with MRM and previous treatment failures, focusing on the perimenstrual window (e.g., from 2 days before to 3 days after the menses) and evaluating the attack frequency (migraine days), intensity, and duration as well as response to painkillers.

Methods This is a report of our real-life experience focusing on the effectiveness and safety of mAbs anti-CGRP in the prevention and treatment of migraine attacks occurring during the perimenstrual window in patients with MRM with at least three or more previous preventive treatments.

At the first administration (T0) and after the six administration (T1) of CGRP- mAbs, all patients underwent an extensive interview to examine clinical parameters of disease severity such as migraine days per month (MMD), menstrual migraine days, menstrual migraine average pain intensity (assessed by numerical rating scale [NRS]), menstrual migraine attacks duration, and response to painkillers.

The percentage of MRM patients experiencing ≥50% reduction of menstrual

migraine days and attack duration was evaluated.

We focused on migraine attacks occurring during the perimenstrual window (from 2 days prior to the first 3 days of menstruation) in patients with MRM evaluat- ing the CGRP-mAbs effects on their frequency, pain severity, duration, and respon- siveness to painkillers.

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Results After six CGRP-mAbs administrations, we observed a statistically significant improvement in frequency, duration, average pain severity, and responsiveness to painkillers of migraine attacks occurring during the perimenstrual window (p < 0.001) as well as MMD.

In a post hoc analysis we considered 21 patients who were receiving only CGRP- mAbs, without other preventive treatments, and we found an equally statistically significant reduction in the frequency, intensity, and duration of menstrual migraine episodes.

The frequency of menstrual migraine changed from baseline (T0) median fre- quency of five migraine days per month (IQR: 1) to T1 median frequency of 2 days per month (IQR: 1) (p < 0.001); the duration of menstrual migraine attacks reduced from a baseline (T0) median duration of 24 h (IQR: 24) to T1 median duration of 7 h (IQR: 11.25); finally, the headache severity improved from a baseline (T0) median intensity (evaluated by NRS) of 8/10 (severe pain; IQR: 1), to T1 median intensity of 6/10 (moderate pain; IQR: 1.5) (p < 0.001).

Discussion In the present real-life experience, we observed a significant reduction in the fre- quency, duration, and intensity of migraine attacks occurring during the perimen- strual window as well as in the response to painkiller in a cohort of MRM patients, with previous treatment failures, during the therapy with CGRP-mAbs for a period of 6 months.

Long half-life triptans, NSAIDs, COX2 ibs, magnesium, and estrogen supple- mentation have been suggested as preventive therapies during the time of highest risk of menstrual migraine attacks in PMM patients with regular menses, to reduce the burden associated with long-term daily preventive medications [211].

Since migraine patients belonging to our sample had previously failed at least three long-term daily preventive treatments and considering the involvement of the CGRP pathway in the mechanisms by which hormonal changes impact on the migraine attacks during menstruation, we explored the effectiveness and safety of CGRP- mAbs in MRM.

Conclusions The present findings demonstrate that mAbs anti-CGRP ligand (Fremanezumab and Galcanezumab) or receptor (Erenumab) could represent an effective and safe thera- peutic strategy for menstrual migraine attacks, significantly improving the fre- quency, duration, intensity, and response to painkillers.

Further studies with a larger sample size and a longer period of observation are needed to better clarify these preliminary findings as well as to demonstrate the effectiveness and safety of mAbs CGRP also in PMM patients.

Acknowledgement A machine generated summary based on the work of Silvestro, Marcello; Orologio, Ilaria; Bonavita, Simona; Scotto di Clemente, Fabrizio; Fasano, Carla; Tessitore, Alessandro; Tedeschi, Gioacchino; Russo, Antonio. 2021 in Pain and Therapy.

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Physician and patient preferences for dosing options in migraine prevention