Galcanezumab in episodic migraine: subgroup analyses of efficacy by high versus low frequency of migraine headaches in phase 3 studies (EVOLVE-1 & EVOLVE-2)

DOI: https://doi.org/10.1186/s10194-019-1024-x

Abstract-Summary Patients with high-frequency episodic migraine (HFEM) have a greater disease bur- den than those with low- frequency episodic migraine (LFEM).

We investigate whether there are differences in galcanezumab efficacy in patients

with LFEM or with HFEM.

Migraine headaches were tracked via electronic patient-reported outcome sys- tem and randomization was stratified by low (LFEM; 4–7 monthly MHDs) or high (HFEM; 8–14 monthly MHDs) frequency.

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In both the LFEM and HFEM subgroups, the overall (Months 1–6) and monthly changes from baseline in monthly MHDs and monthly MHDs with acute medica- tion use compared with placebo were statistically significantly reduced for galcan- ezumab 120-mg and 240-mg.

Galcanezumab (120-mg and 240-mg) significantly decreased the overall and monthly MHDs with nausea and/or vomiting, and with photophobia and phonopho- bia versus placebo in patients with LFEM or HFEM.

In both subgroups, the mean overall (Months 1–6) and monthly percentages of patients with ≥50%, ≥75%, and 100% reduction in monthly MHDs from baseline were statistically significantly greater in patients receiving either dose of galcane- zumab versus placebo.

Galcanezumab (120-mg and 240-mg) significantly improved the Migraine- Specific Quality of Life Questionnaire role function-restrictive domain score as well as the Migraine Disability Assessment total score versus placebo for patients with LFEM or HFEM.

Galcanezumab was as effective in patients with HFEM as in those with LFEM. Associated symptoms, quality of life, and disability were similarly improved in

patients with HFEM or LFEM.

Background The ICHD-3 defines chronic migraine (CM) as 15 or more headache days per month with at least 8 days meeting ICHD criteria for migraine with or without aura [254].

Although using 15 days per month as a divide between EM and CM appears arbitrary, there are meaningful differences in epidemiology, as CM may be more difficult to treat, associated with more comorbidities, with more severe and longer- lasting migraine headaches, and greater functional impact than EM [281].

Unlike CM, there is no standardized definition of LFEM and HFEM, and differ- ent studies have used frequencies from 8 to 14 and 10 to 14 migraine headache days (MHDs) per month to define HFEM [282–284].

The present investigation was undertaken to compare the effect of galcanezumab to placebo in patients with LFEM and HFEM to assess if the treatment effect of galcanezumab differed in these 2 subgroups of patients categorized by migraine headache frequency.

Methods In order to be included in the study, patients also had to have 4 to 14 MHDs per month and at least 2 migraine episodes during the prospective baseline period, as well as 80% compliance in using the electronic diary.

Patients with a history of persistent daily headache, cluster headache, or migraine subtypes (hemiplegic, ophthalmoplegic, or migraine with brainstem aura, or chronic migraine) as defined by ICHD-3 β [285], as well as those previously failing to respond to ≥3 migraine preventive treatments from different therapeutic classes, or presence of a medical condition that would preclude study participation including

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but not limited to pregnancy, suicidal ideation within the past month, history of substance abuse or dependence in the past year, recent history of acute cardiovascu- lar events, and/or serious cardiovascular risk based on history or electrocardiogram findings were excluded.

Results These reductions represent changes of −1.8 (95% confidence intervals [CI]: −2.35, −1.32) and − 1.4 (95% CI: −1.88, −0.84) in monthly MHDs relative to placebo for 120-mg and 240-mg of galcanezumab, respectively, for patients with LFEM and −2.0 (95% CI: −2.56, −1.52) and − 2.1 (95% CI: −2.58, −1.54) in monthly MHDs relative to placebo for 120-mg and 240-mg of galcanezumab, respectively, for patients with HFEM.

The treatment-by-subgroup interaction was not statistically significant indi- cating that the treatment effect did not differ across the LFEM and HFEM subgroups.

There was a statistically significant pairwise subgroup-by-treatment interaction (p = 0.09) for the ≥50% response rate between galcanezumab 120-mg and placebo for the overall (Months 1–6) time period.

Treatment-by-subgroup interactions were not statistically significant for MSQ- RFR and MIDAS total score confirming consistency of treatment effect across the LFEM and HFEM subgroups.

Discussion Galcanezumab given in monthly doses of 120-mg and 240-mg was effective in reducing the numbers of MHDs in patients with LFEM and with HFEM.

The plots of percentage change in the galcanezumab treatment groups show that for every grouping by baseline number of MHDs, there was a similar set of results, with a few patients in most groups showing worsening from baseline, but a substan- tial number of patients in each group showing clinically significant improvement from baseline (>50% reduction in MHDs relative to baseline) for the episodic migraine studies.

These results suggest that galcanezumab is equally effective in patients with epi-

sodic migraine, regardless of headache frequency.

In a recent phase 3 randomized clinical trial, galcanezumab was effective in patients with chronic migraine, and the most common adverse events were related to injection site adverse events [4].

Conclusions Once-monthly galcanezumab reduces the frequency of migraine headache days in patients with LFEM or HFEM.

Acknowledgement A machine generated summary based on the work of Silberstein, Stephen D.; Stauffer, Virginia L.; Day, Katie A.; Lipsius, Sarah; Wilson, Maria-Carmen. 2019 in The Journal of Headache and Pain.

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Instrumental assessment of physiotherapy and onabolulinumtoxin-A on cervical and headache parameters in chronic migraine