Progress in the Treatment of Migraine Attacks: From Traditional Approaches to Eptinezumab

Abstract

Migraine is the second cause of disability and of lost years of healthy life worldwide. Migraine is characterized by recurrent headache attacks and accompanying disabling symptoms lasting 4–48 h. In episodic migraine, attacks occur in less than 15 days per month and in chronic migraine, in more than 15 monthly days. Whilst successful translation of pharmacological discoveries into efficacious therapeutics has been achieved in the preventative therapy of chronic migraine, treatment of acute migraine suffers the lack of effective advancements. An effective treatment affords complete freedom from pain two hours after therapy and provides the absence of the most bothersome symptom (MBS) associated with migraine after 2 h. However, available anti-migraine abortive treatments for acute attacks do not represent an effective and safe treatment for all the populations treated. In particular, the most used specific treatment is represented by triptans that offer 2-h sustained freedom from pain achieved in 18–50% of patients but they are contraindicated in coronary artery disease, stroke and peripheral vascular disease due to the vasoconstriction at the basis of their pharmacologic action. The most novel therapies, i.e., gepants and ditans, are without sufficient post-marketing data for secure use. Here, an attempt is proposed to analyse the rational basis and evidence in favour of investigating the efficacy and safety in acute migraine attacks of eptinezumab, i.e., monoclonal antibody (mAb) directed towards calcitonin gene-related peptide (CGRP) unique for intravenous infusion administration.

Estresa, migraina eta hirugarren belaunaldiko terapiak

“…Diagnostikoa gauzatu ondoren, askotan, tratamendu sintomatiko ez-espezifikoak errezetatzen dira, hau da, migraina-krisi larriei aurre egiteko tratamenduak. Horretarako, parazetamola eta antiinflamatorio ez esteroideoak (AINE), bereziki aspirina, diklofenakoa eta ibuprofenoa, erabiltzen dira [30]. Bestalde, krisiak oso larriak direnean edota AINEak ez badute inolako eraginik, farmako triziklikoak erabiltzen dira.…”

“…Beraz, TRP kanalen aktibazioak CGRP askatzea bultzatuko luke, meningeen kapilarrak dilatatuz, proteina plasmatikoak gehituz eta hantura sustatuz [23]. Horregatik, 5-HT eta CRGP sistemen erregulaziora zuzenduta dauden terapia farmakologikoak, mina zabaltzea eragozten dute, nerbio-sistema zentraleko minaren mekanismoak inhibituz eta garun-azaleko odolhodietako inflamazioa murriztuz [30,33].…”

Pooled Analysis of Real-World Evidence Supports Anti-CGRP mAbs and OnabotulinumtoxinA Combined Trial in Chronic Migraine

“…In fact, botulinum toxin is a multipurpose drug able to provide long-lasting relief in several forms of pain, migraine and primary headache [24,25]. More recently, specific monoclonal antibodies (mAbs) directed towards CGRP ligand (fremanezumab, galcanezumab and eptinezumab, the only administered intravenously and with potential for acute onset of action in attacks [26][27][28][29]) or its receptor complex (erenumab) were developed and approved between 2018 and 2020 by the FDA and the European Medicines Agency (EMA) for the preventive treatment of episodic and chronic migraine [30] to be added to ≥1 established preventive treatment [31]. Unfortunately, even if the anti-CGRP mAbs provide pain relief to difficult-to-treat patients [32], some 40% of nonresponders is present [33].…”

Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety

“…The discovery of the involvement of the calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine ( Scuteri et al, 2019a ) fostered the advance of novel specific small molecules ( Scuteri et al, 2022b ; Scuteri et al, 2022c ) and biotechnological drugs ( Scuteri et al, 2019b ; Scuteri and Bagetta, 2021 ) targeting this peptide ( Scuteri et al, 2020 ). Onabotulinumtoxin A has been approved since 2010 for the treatment of chronic migraine relying on data from the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program ( Diener et al, 2010 ; Aurora et al, 2011 ; Aurora et al, 2014 ).…”