Comparative Effectiveness and Tolerability of the Pharmacology of Monoclonal Antibodies Targeting the Calcitonin Gene-Related Peptide and Its Receptor for the Prevention of Chronic Migraine: a Network Meta-analysis of Randomized Controlled Trials.

Monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or on its receptor are new therapeutic biologics to prevent chronic migraine (CM). Four mAbs acting on the CGRP or on its receptor are new therapeutic biologics to prevent CM. The aim of current network meta-analysis (NMA) was to compare the efficacy and acceptability of CGRP mAbs with onabotulinumtoxinA or topiramate for CM. We included randomized controlled trials (RCTs) examining CGRP mAbs and onabotulinumtoxinA or topiramate in patients with CM. All network meta-analytic procedures were conducted using the frequentist model. The primary outcomes were changes in the monthly migraine days and the 50% response rate. The safety was evaluated with acceptability (i.e., drop-out rate) and rate of any adverse event. This NMA of thirteen RCTs, which, in total, consisted of 5634 participants, demonstrated that a single 300 mg of eptinezumab (mean difference =  - 2.60 days, 95% confidence intervals (95% CIs) =  - 4.43 to - 0.77 compared with placebo) demonstrated the best improvement in monthly migraine days among all interventions. In addition, 675 mg fremanezumab in the first month followed by 225 mg in the second and third months (odds ratio (OR) = 2.96, 95% CIs = 2.20 to 3.97 compared to placebo) was associated with the best response rate among all the interventions. Monthly 140 mg erenumab (MD =  - 2.50 days, 95% CIs =  - 3.83 to - 1.17 compared with placebo) was the best choice for reducing the number of acute migraine-specific medication use days. The safety analysis revealed that loading dose of 240 mg galcanezumab and monthly 240 mg (OR = 0.43, 95% CIs = 0.22 to 0.84) was associated with the lowest drop-out rate; loading dose fremanezumab 675 mg and monthly 675 mg (OR = 1.44, 95% CIs = 1.10 to 1.89), loading dose of 240 mg galcanezumab and monthly 120 mg (OR = 1.37, 95% CIs = 1.02 to 1.84), and single dose of fremanezumab 675 mg (OR = 1.35, 95% CIs = 1.00 to 1.83) were associated with significantly higher rates of AEs than the placebo/control groups. Our NMA indicated that all four CGRP mAbs demonstrated excellent safety, acceptability, and efficacy profiles compared to the traditional prophylaxis for CM. However, because there are several limitations, the findings of the current NMA should be taken into consideration with caution.