The impact of anti-CGRP monoclonal antibodies in resistant migraine patients: a real-world evidence observational study

DOI: https://doi.org/10.1007/s00415-021-10523-8

Abstract-Summary We included migraine patients with ≥ 8 headache days/month that had failed at least three preventive medications.

Patients completed an electronic headache diary including headache days/month, migraine days/month, headache pain intensity (0–3 numerical scale), use of analge- sics and completed Patient-Reported Outcome questionnaires at baseline and after 12 weeks.

After 12  weeks, headache frequency decreased − 9.1 headache days/month

and − 8.5 migraine days/month from baseline.

A 39.5% had a ≥ 50% headache days/month reduction and a 51.6% ≥ 50%

migraine days/month reduction.

In the ≥ 50% migraine days/month-responders group, frequency reduction was − 13,9 migraine days/month from baseline and showed clear improvements for all patient-reported outcomes.

A 14.2% and 26.5% had a ≥ 75% response in headache and migraine days/

month, respectively, and 11.0% showed a 100% migraine days/month reduction.

Patients who were not on other preventive medications had less severe disability and higher ratio of migraine over headache days/month were more likely of being a ≥ 50% migraine days/month-responder. Introduction Calcitonin gene-related peptide (CGRP)-targeted therapies are promising drugs that are being developed to abort migraine attacks as well as to reduce headache fre- quency, headache-related disability and improve patient’s quality of life.

Although patients fulfill criteria for European Headache Federation definition of resistant migraine [198], the reality of our daily outpatient clinic is that we are treat- ing patients who are refractory to every known migraine preventive treatment.

Phase III clinical trials have proved that nearly half of patients treated with anti- CGRP MAbs reduce headache frequency to half with additional benefits on head- ache pain intensity, analgesic use, headache-related disability and quality of life [199] both in episodic and chronic migraine patients with or without previous pre- ventive treatment failures and medication overuse.

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4 Treatment

The aim of this study is to evaluate the frequency and headache-related impact

response to anti-CGRP MAb in clinical sample of resistant migraine patients.

Methods Following national guidelines [200, 201] and European Headache Federation defi- nition of resistant migraine [198], all recruited patients fulfilled ICHD-3 criteria for CM or EM with a headache frequency ≥8 days/month, with or without analgesic medication overuse that had previously failed at least three preventive medications, being OnabotulinumtoxinA one of them in CM patients.

Migraine-related clinical burden was assessed with the following Patient- Reported Outcomes (PRO) questionnaires: Migraine Disability Assessment (MIDAS) [202], Headache Impact Test 6 (HIT-6) [203], Migraine-Specific Quality- of-life version 2.1 (MSQ) [204], Beck Anxiety Inventory (BAI) [205] and Beck Depression Inventory-II (BDI-II) [206] and subjective cognitive impairment during migraine attacks (Mig-SCog) [207].

One month prior the first dose with anti-CGRP MAbs and during all the treat- ment period, patients were trained to complete an electronic headache diary (eDi- ary) where they recorded presence of headache, pain intensity using a 0–3 numerical scale [0—nopain,1—mild,2—moderate,3—severepain] and use of acute medica- tion to treat headache.

Paired t test or Wilcoxon signed-rank test was computed, according to vari- able distribution, to study outcome variables changes after three months of treatment.

Variables included in this multivariate analysis were either based on statistical significance from bivariate tests or measures that we considered clinically relevant to migraine patients.

Ethics Approval and Patients’ Consent The study was approved by the Vall d’Hebron Ethics Committee.

All patients gave a written informed consent for the analysis of patients’ data

which were collected according to Spanish regulation on clinical trials.

Results In regards to ≥75% MDM RR, we found that responder patients were those who had lower scores in migraine disability (MIDAS, NR: 74.0[79.3] vs. R: 55.0[88.0]; p = 0.009), headache-related impact (HIT-6, NR: 66.8  ±  5.4 vs. R: 64.8  ±  5.2; p = 0.038), QoL-related impact (MSQTOTAL, NR: 70.1 ± 17.8 vs. R: 59.3 ± 18.1; p = 0.001), anxiety (BAI; NR: 20.0[22.5] vs. R: 12.0[18.0]; p = 0.001), depression (BDI-II; NR: 14.0[23.0] vs. R: 8.0[11.5]; p = 0.009) and subjective migraine dis- ability (MigScog, NR: 9.5 ± 4.7 vs. R: 7.2 ± 4.3; p = 0.008).

No statistically significant variables were associated with 100% RR in HDM but responder patients with 100% MDM reduction (11.0%, 17/155) showed in addition to the lower scores in all PRO questionnaire (MIDAS, HIT-6, MSQTOTAL, BAI, BDI-II and MigScog), higher female patients with menopause (NR: 32.6% vs. 52.9%; p = 0.029) and lower failures to ≥4 previous preventive classes (NR: 90.6% vs. R: 76.4%; p = 0.033).

4.2 Preventive Treatment

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Discussion After three months of treatment with anti-CGRP MAb, we observed not only a fre- quency reduction of 9.1 HDM and 8.5 MDM from baseline, but also a decrease in mean pain intensity of nearly 1 point in a 0–3 scale and a reduction of 6.4 analgesic use days.

Regarding headache frequency responder rates, a 39.5% of our cohort have a ≥50% reduction of HDM at month 3, and up to 51.6% of patients had a ≥50% reduction in moderate to severe days (MDM).

The benefit of anti-CGRP MAbs in responders has also been measured using patient-reported outcome scales, showing also clear and meaningful reductions in headache-related disability and quality of life in the responder group.

The quick initial change in headache frequency and the reduction in migraine impact on treatment responders undoubtedly justifies the use of anti-CGRP MAb in real-world clinical practice and raises awareness among neurologists and healthcare providers on the use of migraine-specific preventive therapies in our patients.

Conclusion Anti-CGRP MAb prove to be effective and safe treatments in refractory migraine patients in real-life clinical practice.

Our efficacy is superior to the data from controlled clinical trials showing mean- ingful reductions in headache frequency, pain intensity and impact on daily life in a cohort or highly disabled migraine patients.

Acknowledgement A machine generated summary based on the work of Torres-Ferrús, Marta; Gallardo, Victor J.; Alpuente, Alicia; Caronna, Edoardo; Gine-Cipres, Eulalia; Pozo-Rosich, Patricia. 2021 in Journal of Neurology.

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