[Integrating new migraine treatments into clinical practice. Part 2 : preventive treatment]. / Intégration des nouveaux anti-migraineux dans notre pratique clinique . Partie 2 : traitement préventif.

Migraine is the most common neurological disorder and can be very debilitating. While traditional (and older) oral preventive treatments have helped numerous patients to date, their therapeutic efficacy is often low, and adverse event profiles are troublesome. However, the coupled progress of biochemistry and molecular biology as well as the application of advanced drug design methods have led to a therapeutic renewal with, in particular, the advent of monoclonal antibodies blocking CGRP («Calcitonin Gene- Related-Peptide¼) transmission. We provide an overview of the preventive pharmacologic options with both older oral treatments and new ones such as botulinum toxin and the newly marketed CGRP monoclonal antibodies. The latter seem particularly interesting because they have an effectiveness at least equivalent to most oral treatments with much better tolerance and compliance. Unfortunately, their very high cost confines them to a fourth line of therapy in Belgium, a disappointment for both specialists in migraine therapy and patients who suffer from frequent migraine crisis. We finally propose a rational (and Belgian) pharmacological approach of migraine preventive treatment.

La migraine est la maladie neurologique la plus fréquemment rencontrée et elle peut être très handicapante. Si les traitements préventifs oraux traditionnels (et anciens) ont déjà aidé de nombreux patients à ce jour, il faut bien reconnaître que leur efficacité s'est souvent avérée faible et avec un profil d'effets indésirables peu favorable. Heureusement, les progrès couplés de la biochimie et de la biologie moléculaire de même que l'application de méthodes avancées de conception de médicaments ont entraîné un renouveau thérapeutique avec, notamment, l'avènement des anticorps monoclonaux anti-CGRP («Calcitonin Gene-Related-Peptide¼). Nous présentons les différentes options pharmacologiques de traitement préventif, que ce soient les traitements oraux anciens, mais aussi les nouveaux traitements récemment remboursés en Belgique que sont la toxine botulinique et surtout les anticorps monoclonaux anti-CGRP. Ces derniers semblent particulièrement intéressants car ils ont une efficacité au minimum équivalente à la plupart des traitements oraux, avec une bien meilleure tolérance et observance thérapeutique. Malheureusement, leur prix très élevé les cantonne actuellement à une quatrième ligne thérapeutique en Belgique, une déception pour les médecins spécialistes de la migraine et les patients invalidés par de fréquentes crises de migraine. Nous clôturons par une proposition d'algorithme thérapeutique adapté à la Belgique (et à ses critères de remboursement).

Erenumab for Migraine Prevention in a 1-Year Compassionate Use Program: Efficacy, Tolerability, and Differences Between Clinical Phenotypes.

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) (n = 80) to chronic migraine (CM) (n = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) (p = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment (p < 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) (p < 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) (p < 0.05). There was no significant efficacy difference between low (4-7 migraine days/month, n = 22) and high frequency (8-14 days, n = 59) EM nor between patients with CM with (n = 50) or without (n = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies.

Cosmetic Injection of Botulinum Toxin Unmasking Subclinical Myasthenia Gravis: A Case Report and Literature Review.

Cosmetic or therapeutic use of botulinum toxin type A (BoNT-A) is usually safe but can rarely cause iatrogenic botulism. Iatrogenic botulism and myasthenia gravis (MG) share similar clinical features, because both BoNT-A and anti-acetylcholine receptorantibodies impair neuromuscular transmission. We report a patient who underwent cosmetic BoNT-A injection and later developed serious local and systemic adverse reactions. The peculiarity of this case is that a latent seropositive MG was eventually discovered, suggesting that both iatrogenic botulism and MG contributed to the clinical picture. This patient is one of the less than 10 reported cases worldwide in whom MG was unmasked by BoNT-A injection. He is the first to be assessed in detail by single-fiber electromyography. This case emphasizes the risk associated with BoNT-A injection in patients with subclinical impairment of neuromuscular transmission and prompts the search for MG in case of exaggerated response.