Galcanezumab for the Management of Migraine: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

Introduction Migraine is a frequent neurological condition manifested by several episodes of headache. Calcitonin gene-related peptide (CGRP) has been shown to play a key role in the pathophysiology of migraine. Galcanezumab is a monoclonal antibody that binds CGRP and inhibits its action, without affecting the CGRP receptor. The aim of this study is to carry out a systematic review and meta-analysis of all randomized placebo-controlled trials that evaluated the efficacy of galcanezumab (120 mg or 240 mg) for the management of migraine. Methods We screened four databases (PubMed, SCOPUS, Embase, and Cochrane Central) from inception to October 10, 2020. Studies meeting the following criteria were included: (i) Patients: individuals with migraine, (ii) Intervention: galcanezumab at a dose of 120 mg or 240 mg, (iii) Comparator: placebo, (iv) Outcomes: prespecified efficacy and safety outcomes, and (v) Study design: randomized placebo-controlled trials. Efficacy outcomes included change in migraine headache days (MHDs), change in MHDs with acute medication use, patient global impression of severity (PGI-S) score, migraine-specific quality of life role function-restrictive domain (MSQ RF-R) score, and migraine disability assessment (MIDAS) score. Safety outcomes included frequency of injection-site pain, nasopharyngitis, and upper respiratory tract infection (URTI). Moreover, we used the Cochrane Collaboration's risk of bias tool to assess the risk of bias of the included studies. Review Manager Software, version 5.4.1, was used for statistical analysis. Mean difference and risk ratio with 95% confidence interval were used to analyze continuous and dichotomous outcomes, respectively. We used the fixed-effects and random-effects models to analyze homogeneous and heterogeneous data, respectively. Results A total of six studies comprising 4,023 patients were included in this systematic review and meta-analysis. When compared to placebo, both doses of galcanezumab were highly effective in decreasing MHDs (p<0.001), reducing MHDs with acute medication use (p<0.001), and improving the PGI-S score (p<0.001). On the other hand, MSQ RF-R and MIDAS scores were significantly enhanced only in the 240-mg dose group (p<0.001). With regard to side effects, the rates of injection-site pain and nasopharyngitis did not substantially differ between galcanezumab (inclusive of 120 mg and 240 mg) and placebo groups. Nonetheless, when compared to placebo, galcanezumab 120 mg, but not galcanezumab 240 mg, substantially correlated with a higher rate of URTI. Conclusions Galcanezumab is clinically safe and efficient for the management of migraine, and the use of a higher dose increases its efficacy. Future research directions should be geared toward determining the optimal dose of galcanezumab in the management of patients with migraine. Moreover, head-to-head comparative studies between galcanezumab and other related anti-CGRP receptor monoclonal antibodies are warranted.