Only one study reported the pharmacists were aware of group assignment

Only one study reported the pharmacists were aware of group assignment. CGRP-mAbs vs. placebo (weeks 1C4: SMD ?0.49, 95% CI ?0.61 to ?0.36; weeks 5C8: SMD ?0.43, 95% CI ?0.56 to ?0.30; weeks 9C12: SMD ?0.37, 95% CI ?0.49 to ?0.24). 50% and 75% responder rates (OR 2.59, 95% CI 1.99 to 3.37; and OR 2.91, 95% CI 2.06 to 4.10) were significantly increased compared with placebo. There was no significant difference in total adverse events (OR 1.17, 95% CI 0.91 to 1 1.51), and the main adverse events including upper respiratory tract infection (OR 1.44, 95% CI 0.82 to 2.55), nasopharyngitis (OR 0.59, 95% CI 0.30 to 1 1.16), nausea (OR 0.61, 95% CI 0.29 to 1 1.32), injection-site pain (OR 1.73, 95% CI 0.95 to 3.16) and back pain (OR 0.97, 95% CI 0.49 to 1 1.90) were not obviously changed compared with placebo control, but the results showed significant increase of Istaroxime dizziness in CGRP-mAbs vs. placebo (OR 3.22, 95% CI 1.09 to 9.45). Conclusions This meta-analysis suggests that CGRP-mAbs are effective in anti-migraine therapy with few adverse reactions, but more and larger sample-size RCTs are required to verify the current findings. Keywords: Migraine, Monoclonal antibodies to calcitonin gene-related peptide, CGRP-mAb, Meta-analysis Background Migraine is a common, chronic neurovascular disorder with a female prevalence of 17% and a male prevalence of 9%, typically characterized by disabling attacks of severe headache and autonomic nervous system dysfunction [1, 2]. Different pathological and genetic mechanisms may be related to a variety of clinical manifestations. The etiology and pathogenesis of migraine are not yet completely understood. Although studies on molecular players involved in the disease are incomplete, recent preclinical and clinical findings indicate that there is a clear correlation between migraine and the release of the neurotransmitters and vasoactive substances, such as 5-hydroxytryptamine (5-HT) [3C5], calcitonin gene-related peptide (CGRP) [6C8], and dopamine (DA) [9C11]. Over the past decades, ergotamine and the triptans, both of which are serotonin 5-HT agonists, have been proved effective for treating acute migraine, and are widely used in clinical practice [12, 13]. However, a significant number of migraine cases do not respond to these therapies. In addition, adverse effects such as cardiovascular concerns limit their use [14]. Calcitonin gene-related peptide (CGRP), is recognized as a crucial peptide in the pathophysiology of migraine, and has been increasingly investigated. CGRP receptor antagonists (CGRP-RAs), including olcegepant (BIBN4096BS), telcagepant, MK-3207 and MK-0974, have Istaroxime shown considerable efficacy in the treatment of migraine. However, several were discontinued due to concerns for hepatotoxicity Istaroxime with daily use [15C20], others were discontinued for other (or unknown) reasons. Recently developed CGRP-mAbs were triggered much interest Istaroxime in the migraine community [21C24]. LY2951742 (Arteus Therapeutics), ALD403 (Alder Biopharmaceuticals), TEV-48125 (previously named as LBR-101) (Labrys Biologics-TEVA) and AMG 334 (Amgen) have completed Phase II and Tmem26 are undergoing III clinical trials [24]. These drugs have show anti-migraine activity with few adverse events. However, their clinical efficacy and safety lack systematic evaluation. Therefore, we performed a systematic review Istaroxime and meta-analysis on the overall efficacy and safety of CGRP-mAbs for migraine based on recent clinical findings. Methods Literature search and inclusion criteria Two reviewers (MH and HYX) independently searched PubMed, Cochrane Library and Baidu Scholar for articles by entering headache or migraine and monoclonal anti-CGRP antibody or monoclonal antibody to calcitonin gene-related peptide as search terms. We then examined all articles and their reference lists to expand potentially relevant articles. The searches were limited to human studies published in English from inception of the databases to Nov 1, 2016. The articles were included in the meta-analysis if they met the following criteria: (1) randomized controlled trials (RCTs) evaluating the efficacy and safety of CGRP-mAbs for migraine; (2) no restrictions on population characteristics, blind.