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

DOI: https://doi.org/10.1186/s10194-019-1018-8

Abstract-Summary This retrospective pooled analysis included completers of the open-label extension study phase for the preventive treatment of chronic migraine with galcanezumab (NCT02614261; 9 months) and erenumab (NCT02174861; 12 months) in a single headache center.

We compare migraine data until week 12 after open-label treatment completion, when patients did not have any pharmacological preventive medication, to study baseline values of the double-blind trial period, and to the last 4 weeks of the open- label extension.

The mean number of monthly migraine days was 18.38 ± 3.74 at baseline, and

12.19 ± 4.53 in the last 4 weeks of the open-label extension (p < 0.001).

Monthly migraine days remained significantly reduced compared to baseline during the entire 12-week observation period after open-label termination (p = 0.002), with a reduction of 5.38 ± 4.92 in weeks 1–4 (p = 0.001), 4.75 ± 4.15 in weeks 5–8 (p = 0.001), and 3.93 ± 5.45 in weeks 9–12 (p = 0.014).

There was no significant difference in monthly migraine days between the 12 weeks after open-label termination and the last 4 weeks of the open-label phase (p = 0.228).

In this small, self-selected cohort, the results indicate a therapeutic effect of monoclonal antibodies targeting the CRGP pathway in chronic migraine prevention after treatment termination up to 12 weeks.

Extended: Monthly migraine days remained significantly lower during the entire

observation period compared to baseline with a small increase over time.

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4 Treatment

Background Erenumab (NCT02174861) and galcanezumab (REGAIN, NCT02614261) showed a significant reduction of monthly migraine days in chronic migraine during the 3-month double-blind placebo-controlled treatment phase [4, 226].

We assessed the course of chronic migraine following the termination of preven- tive open-label therapy with erenumab and galcanezumab, when patients were with- out any preventative medication.

Methods Completers of the 12-week double-blind phase could switch to a 52-week open- label extension and received initially a monthly dose of 70 mg erenumab s.c.

This analysis included data from patients who recorded routine headache data for at least 12 weeks after termination of the open-label study phase, and also did not receive any migraine prophylactic medication during this period.

We collected data for galcanezumab using the patients’ electronic trial diary dur- ing baseline (4  weeks before randomization), the last 4 weeks of the open-label extension, and up to week 12 after open-label termination (i.e. weeks 5–16 after last study drug injection).

For erenumab, we analyzed electronic records for the 4-week baseline period prior to randomization and the last 4 weeks of the open-label extension, whereas data from week 1 to week 12 after open-label termination (i.e. weeks 5–16 after last study drug injection) were collected from standardized paper headache diaries.

Results Patients recorded 18.38 (±3.74) monthly migraine days.

Four chronic migraine patients recorded ≤15 monthly migraine days during the entire observation period, while only two patients had an increase of ≥2 migraine days in weeks 9–12 vs. baseline.

Discussion Termination of preventive treatment with galcanezumab and erenumab in patients with chronic migraine did not lead to headache return to baseline levels within a period of 12 weeks.

In the phase II trial for galcanezumab in the prevention of episodic migraine, the 50-mg dose did not meet the primary endpoint, defined as reduction of monthly migraine days in the third treatment month vs. baseline [270].

The number of migraine days increased over time, beginning within the first 4 weeks on placebo and was significantly higher than in patients who continued topi- ramate prophylactic treatment [271].

Real-life data on the use of mAbs as migraine preventive medication revealed a relevant decrease in monthly migraine days after only 1 month of treatment: In an Italian cohort, 65 patients with chronic migraine treated with erenumab reported a reduction of 12.2 monthly migraine days after 4 weeks, along with a decrease in medication use, pain intensity, and disability [227].

4.3 Results

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Conclusions Our results suggest continuous efficacy of mAbs against CGRP/CGRP receptor in the prevention of chronic migraine up to 12 weeks after treatment discontinuation.

Acknowledgement A machine generated summary based on the work of Raffaelli, Bianca; Mussetto, Valeria; Israel, Heike; Neeb, Lars; Reuter, Uwe. 2019 in The Journal of Headache and Pain.

A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine