Recent Advances in Pharmacotherapy for Episodic Migraine

DOI: https://doi.org/10.1007/s40263-019-00665-9

Abstract-Summary In 2018, three calcitonin gene-related peptide (CGRP) pathway monoclonal anti- bodies, erenumab, fremanezumab and galcanezumab, were approved in various parts of the world, including Europe and the US, and another, eptinezumab, is pend- ing, for the prevention of migraine.

Episodic migraine treatment is reviewed, although these medicines are approved

and are just as effective for chronic migraine.

These new medicines usher a new phase in the preventive management of

migraine with migraine-specific treatments.

Data from phase III trials of CGRP pathway monoclonal antibodies have shown

they are efficacious, with adverse effect rates comparable to placebo.

Beyond this, gepants will see the most disruptive development in migraine man- agement in generations with medicines that can have both acute and preventive effects, the latter evidenced by data from the discontinued drug telcagepant and the early-phase drug atogepant.

One can expect no risk of medication overuse syndromes with gepants since the

more patients take, the less migraines they have.

During the next years, as experience with monoclonal antibodies grows in clini-

cal practice, we can expect an evolution in migraine management to take shape.

Introduction Prior to 2018, no migraine-specific, mechanism-targeted preventives entered clini- cal practice.

CGRP pathway monoclonal antibodies have recently become available for the

prevention of both episodic and chronic migraine.

Four CGRP pathway monoclonal antibodies have recently completed phase III

trials in the prevention of both episodic and chronic migraine [1–11].

In 2018, erenumab, galcanezumab and fremanezumab were approved by a num- ber of regulators, including the FDA and the European Medicines Agency, for the prevention of both episodic and chronic migraine; eptinezumab is undergoing evaluation. We focus our review on the newly approved CGRP monoclonal antibodies in epi- sodic migraine, and also outline the results of the phase III trials of eptinezumab, rimegepant and ubrogepant.

The Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies For patients in the HALO-EM study who had previously failed at least one preven- tive and were treated with either 225 mg monthly or 675 mg quarterly, there was a change in MMD of −3.7 (p = 0.0015) and −3.3 (p < 0.001), respectively, compared with −1.3 in the placebo arm [12].

4.1 Acute Treatment

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Pooled subgroup analysis of patients within the EVOLVE 1 and EVOLVE 2 studies who had previously tried two or more preventives unsuccessfully, showed they also reported a reduction in MMD with galcanezumab 120 mg of −3.45 days (p < 0.001) and −3.85  days (p < 0.001), compared with −0.81  in the placebo group [13].

The LIBERTY study was a phase IIIb trial with a erenumab 140 mg treatment

arm, where, to be eligible, patients had to have failed two to four preventives.

Acute Therapies on the Horizon An orally dissolving 75  mg tablet has also been assessed, with similar findings, where pain freedom 2 h postdose was achieved in 21.2% of patients compared with 10.9% in the placebo arm (p < 0.0001), and relief of the most bothersome symptom (MBS) after 2 h was achieved in 35.1% of patients compared with 26.8% in the placebo group (p = 0.0009) [14].

In ACHIEVE I, the proportion of patients achieving pain freedom at 2  h was 19.2% of the 50 mg group (p = 0.0023) and 21.2% in the 100 mg (p = 0.0003) com- pared with 11.8% in the placebo group.

The proportion of patients achieving freedom of MBS at 2 h was 38.9% in the

50 mg group (p = 0.0129) compared with 27.8% in the placebo group.

Conclusions The approval of new preventive therapies with proven efficacy and without the adverse effect profile of existing nonspecific preventives represents the beginning of an exciting change in clinical practice in the management of episodic migraine.

Of interest is the day 1 results for eptinezumab, suggesting that it could be used

in an acute setting with rapid preventive effect.

Current evidence of the described preventives and acute therapies have the poten-

tial to address the unmet need in migraine management.

The evidence suggests these therapies are more tolerable than their predecessors, however they will require ongoing surveillance as they move from the regulated populations of clinical trials to our heterogeneous patient populations.

Acknowledgement A machine generated summary based on the work of Chan, Calvin; Goadsby, Peter J. 2019 in CNS Drugs.

Improving Medication Adherence in Migraine Treatment