Efficacy and safety of anti-calcitonin gene-related peptide monoclonal antibodies for treatment of chronic migraine: A systematic review and network meta-analysis

Background & Objective: To conduct a systematic review and network meta-analysis of all randomized trials investigating effects of anti-calcitonin gene related peptide monoclonal antibodies (anti-CGRP mAbs) on adult patients with chronic migraine. Methods: MEDLINE, Embase and Cochrane Central Register of Controlled Trials searched from inception to July 2020; and clinical trial registries. The network meta-analysis was conducted in Bayesian framework using OpenBUGS and R, with the random effects model selected to allow for apparent heterogeneity between studies in the treatment comparison effects. Results: Overall 38 studies (5164 chronic migraineurs in seven randomized trials) were included with treatment course of at least 12 weeks. Fremanezumab 675 + 225 + 225 mg QM (SC) injections were numerically more effective in lowering migraine days with lower MDs compared to eptinezumab 10 mg (IV) (MD:-1.52, 95% CrIs: -4.24, 0.99), eptinezumab 30 mg (IV) (MD:-0.33, 95% CrIs:-3.02, 2.16), eptinezumab 100 mg (IV) (MD: -0.59, 95% CrIs:-2.80, 1.42), eptinezumab 300 mg (IV) (MD:-0.02, 95% CrIs:-2.29, 1.98), erenumab 70 mg QM (SC) (MD:-0.17, 95% CrIs:-2.84, 2.25), erenumab 140 mg QM (SC) (MD:-0.18, 95% CrIs:-2.87, 2.26), fremanezumab 675 mg (SC) (MD:-0.30, 95% CrIs:-1.81, 1.14), galcanezumab 120 mg QM (SC) (MD:-0.71, 95% CrIs:-3.44, 1.55) and galcanezumab 240 mg QM (SC) (MD:-0.58, 95% CrIs:-3.09, 1.89), however the results were non-significant. Similarly, the anti-CGRP mAbs were also observed to have comparable safety and immunogenicity with no significant differences. Conclusions: Although all doses of anti-CGRP mAbs have comparable efficacy, safety and tolerability based on uncertainties in indirect comparisons for all outcomes, the calculated effect estimates numerically favored high doses of subcutaneous fremanezumab and intravenous eptinezumab as the effective therapy with acceptable safety and tolerability for short term prevention of chronic migraine.