Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine – an updated systematic review and meta-analysis

Abstract

Background: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. Methods: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. Results: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = − 1.44, 95% CI = (− 1.68,− 1.19)] and acute migraine-specific medication days [WMD = − 1.28, 95% CI = (− 1.66,− 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. Conclusions: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.

Changing levels of sex hormones and calcitonin gene-related peptide (CGRP) during a woman’s life: Implications for the efficacy and safety of novel antimigraine medications

“…Phase III trials with the antibodies as preventive treatment for migraine have shown a significant improvement in migraine with a favorable tolerability profile when compared to the current prophylactics. Unfortunately, even though they were specifically developed for the treatment of migraine, not all patients benefit from these antibodies [8].…”

“…Due to their long plasma half-life (about a month), the antibodies are only suitable for prophylactic treatment [32] and are administrated monthly or once every three months. This, combined with an excellent tolerability in clinical trials [8], will lead to a higher compliance rate when compared to the current preventive migraine treatments.…”

“…At the moment three antibodies against CGRP (fremanezumab, galcanezumab and eptinezumab), and one against the CGRP receptor (erenumab) have been developed. In recent years multiple phase III trials have been performed [8], which have all shown a statistically significant J o u r n a l P r e -p r o o f advantage compared to placebo. About 40-60% of participants had at least 50% reduction in migraine days.…”

Migraine patients in Germany - Need for Medical Recognition and New Preventive Treatments: Results from the PANORAMA Survey

“…This and the probably increasing frustration of patients mirror the claim for novel migraine therapies, made by the physicians. The development and approval of a new therapeutic approach targeting the CGRP pathway by monoclonal antibodies, as well as the development of novel biological prophylactic migraine treatments [11][12][13][14][15][16][17] with increased e cacy, tolerability and safety hold the promise of overcoming former therapy drawbacks. In this context, a large controlled clinical trial investigating erenumab in patients with episodic migraine showed its e cacy in reducing the number of monthly migraine days and use of acute medication, as well as an improvement in Physical-Impairment-and Everyday-Activities Scores 18 .…”

Fremanezumab: a disease-specific option for the preventive treatment of migraine, including difficult-to-treat migraine

“…Four mAbs, fremanezumab, erenumab, galcanezumab, and eptinezumab, were investigated in clinical trials for CM and EM and are approved for the preventive treatment of migraine in the United States and/or Europe [12][13][14][15][16][17][18]. All 4 of these CGRP pathway-targeted mAbs have effectively reduced the frequency of migraine days with a good tolerability profile [1,11,19,20].…”