A prospective real-world analysis of erenumab in refractory chronic migraine

DOI: https://doi.org/10.1186/s10194-020-01127-0

Abstract-Summary This is a prospective single centre real-world audit conducted in patients with CM with and without medication overuse, refractory to established preventive medica- tions, who received monthly erenumab for 6 months.

4.2 Preventive Treatment

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The mean reduction in monthly migraine days was 6.0 days at month 3 (P = 0.002)

and 7.5 days at month 6 (P < 0.001) compared to baseline.

At month 3, 49%, 35% and 13% and at month 6, 60%, 38% and 22% of patients

obtained at least a 30%, 50% and 75% reduction in migraine days, respectively.

The percentage of patients with medication overuse was reduced from 54% at

baseline to 20% at month 3 and to 25% at month 6.

Compared to baseline, the mean reduction of Headache Impact Test-6 score was 7.7 points at month 3 (from 67.6 ± 0.4 to 59.9 ± 0.9) (P < 0.001) and of 7.5 points at month 6 (60.1 ± 1.3) (P = 0.01).

The percentage of patients with severe headache-related disability (HIT-6: 60–78) was reduced from 96% at baseline to 68% after three monthly treatments and to 59% after six treatments.

At least one side effect was reported by 48% of patients at month 1, 22% at

month 3 and 15% at month 6.

Erenumab may be an effective and well tolerated therapy for medically refrac-

tory CM patients with and without medication overuse.

Extended: This is a registered prospective clinical audit evaluating the effective-

ness, safety and tolerability of erenumab in adults with refractory CM.

The mean reduction in abortive treatment days was statistically significant at

month 3 (3.3 ± 0.7, P = 0.01) but not at month 6 (4.0 ± 3.1, P = 1.1).

At month 3, 49%, 35% and 13% out of the 100 patients obtained at least a 30%,

50% and 75% reduction MMD, respectively.

The percentage of patients with MOH was reduced from 54% at baseline to 20%

after three treatment and to 25% after 6 treatments.

The percentage of patients with severe headache-related disability was reduced from 96% at baseline to 68% after three monthly treatments and to 59% after six treatments.

Introduction The cornerstone strategy to reduce symptoms in CM includes preventive treatments, however a significant minority of CM patients fails to respond or tolerate numerous preventive treatments [263].

Refractory CM is still a debated definition, but it essentially refers to the group of difficult-to-treat CM patients who fail to respond/tolerate at least two or three classes/medications amongst the ones considered effective in migraine prevention [264, 265].

A recent consensus of the European Headache Federation (EHF) has proposed a distinction of the difficult-to-treat migraine patients into resistant, for those who fail to respond or tolerate three drug classes with established evidence in migraine; and refractory, for those patients who fail all drug classes with established evidence in migraine [266].

In September 2018 Erenumab (Aimovig™), a CGRP receptor monoclonal anti- body, was made available free-of-charge in the United Kingdom (UK) for the pre- vention of CM in patients who failed at least three preventive treatments, as part of an agreement between Novartis and the National Health System (NHS) Trusts across the UK.

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4 Treatment

Methods For patients who underwent a trial with botulinum toxin type A (BoNT/A), failure to obtain at least 30% reduction in headache days after two sets of injections was considered treatment failure as per NICE UK guidance [267].

Patients were required to produce a baseline headache diary and HIT-6 score for at least one month prior to treatment initiation and to continue filling the headache diary on a daily basis along with HIT-6 scores every month for the duration of the trial.

Secondary efficacy outcomes included: changes from baseline in mean monthly headache days (MHD), change in mean monthly headache-free days, 30%–50%–75% responders (patients who reported respectively a 30%–50%–75% reduction in mean MMD).

An “abortive treatment intake day” was considered any day where patients con-

sumed abortive treatments for attempted headache relief.

The efficacy of erenumab in treated patients was assessed by our specialised

headache team every three months for the duration of the trial.

4.3

Results

The proportion of patients with a daily headache pattern was reduced from 41% at baseline, to 22% after three and to 21% after six treatments with erenumab.

At month 6, 60% of patients (N = 44/73) achieved at least 30% reduction in mean

MMD and therefore continued the treatment.

Compared to baseline, 16/43 patients obtained > 30% but < 50% reduction in mean MMD and 27/43 patients obtained < 30% reduction in mean MMD at month 3. Of the 27 patients who did not achieve a 30% reduction in mean MMD after three monthly injections with erenumab 70 mg, five patients (19%) achieved at least a 30% reduction in mean MMD at month 6, after increasing the dose to 140 mg for three consecutive months and hence continued the treatment further.

The percentage of patients with severe headache-related disability was reduced from 96% at baseline to 68% after three monthly treatments and to 59% after six treatments.

Discussion The month-3 reduction in MMD with erenumab 70 mg reported in our analysis was similar to the main endpoint of the pivotal phase 2 CM clinical trial both when the whole study population was considered but also when the subgroup of patients who failed at least two preventive treatments was analysed [3, 268].

Our data were similar to the outcome of the subgroup analysis of 274 CM patients with MOH treated with erenumab or placebo, showing no significant difference in treatment effect between the group with MOH and non-MOH [269].

In the subgroup analysis of the pivotal phase 2 clinical trial, patients with prior preventive treatment failure treated with erenumab reported a higher proportion of AEs compared to placebo (42–58% depending upon the different doses) [268].

4.3 Results

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Conclusion Erenumab was effective in the prevention of migraine symptoms in our highly refractory CM patients with and without MOH.

Erenumab’s beneficial effect seems to be sustained, progressive overtime and not

influenced by the level of patients’ refractoriness.

Treatment-related AEs reduced overtime, confirming its favourable tolerability

profile.

Acknowledgement A machine generated summary based on the work of Lambru, Giorgio; Hill, Bethany; Murphy, Madeleine; Tylova, Ivona; Andreou, Anna P. 2020 in The Journal of Headache and Pain.

Erenumab and galcanezumab in chronic migraine prevention: effects after treatment termination