Safety and Efficacy of Fremanezumab for the Prevention of Migraine: A Meta-Analysis From Randomized Controlled Trials

Abstract

Background: Fremanezumab (TEV-48125) is a fully-humanized immunoglobulin G isotype 2a selective monoclonal antibody that potently binds to calcitonin gene-related peptide (CGRP). It is one of the novel therapeutic drugs for the prevention of migraine, which is one of the most common neurological diseases worldwide. Several controlled trials have been conducted to investigate the safety and efficacy of fremanezumab, however, there is no systematic review of the existing literature has been performed. Hence, in our study, we performed a meta-analysis to investigate the safety and efficacy of fremanezumab for the prevention of migraine. Method: Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to August 2019 for randomized controlled trials (RCTs). Five RCTs with 3,379 patients were finally included in our study. Result: We pooled 3,379 patients from 5 RCTs; the primary endpoints were mean monthly migraine and headache days, baseline to week 12. We found that fremanezumab led to a significant reduction in migraine days (P < 0.0001) and headache days (P < 0.0001) during 12 weeks compared with placebo. Moreover, after using fremanezumab, the risk of at least one adverse event (AE) (P = 0.001) and AE related to the trial regimen (P = 0.0005) significantly increased compared with the placebo. Conclusions: Fremanezumab showed good efficacy for the prevention of migraine. The administration of fremanezumab can cause some mild adverse events but no serious adverse events.

Pharmacokinetics, Pharmacodynamics and Drug–Drug Interactions of New Anti-Migraine Drugs—Lasmiditan, Gepants, and Calcitonin-Gene-Related Peptide (CGRP) Receptor Monoclonal Antibodies

“…Concomitant use of acute migraine treatments (analgesics, ergots, and triptans) and migraine preventive medicinal products during the clinical studies did not affect pharmacokinetics of fremanezumab [92,93].…”

“…Maximum plasma concentration of fremanezumab after a single administration is reached after 5-7 days (from 3 to 20 days) [16,84,[91][92][93][94][95][96][97], and the absolute bioavailability is 55% and 66% for 225 mg and 900 mg, respectively. A steady-state is achieved within approximately 168 days [91][92][93][94][95][96][97]. There is no need to modify the dosage in the elderly or in patients with mild to moderate renal or hepatic impairment [92,93].…”

“…A steady-state is achieved within approximately 168 days [91][92][93][94][95][96][97]. There is no need to modify the dosage in the elderly or in patients with mild to moderate renal or hepatic impairment [92,93]. Using population pharmacokinetic modeling and simulation of fremanezumab in healthy subjects and patients with migraine, it was shown, however, that higher body weight was associated with a lower exposure of fremanezumab (an increased central clearance and distribution volume) [96].…”

Effects of Anti-CGRP monoclonal antibodies for episodic and chronic migraine on migraine characteristics, disability, impact and quality of life beyond 3 months of treatment: A Systematic review and Meta-analysis

“…Exploratory literature search revealed that there are some systematic reviews and meta-analysis on RCT's that analyze the efficacy, safety and tolerability of anti-CGRP monoclonal antibodies on migraine prophylactic treatment: on episodic migraine (22,23) , chronic migraine (24) , episodic and chronic migraine (25,26) , with galcanezumab (27)(28)(29)(30) , fremanezumab (31) or erenumab (32) but just one systematic review analyzed the migraine related disability, impact and health related quality of life in migraine patients treated with galcanezumab (27) . One systematic review and meta-analysis that present data on anti-CGRP monoclonal antibodies after 3 months but include phase 2 RCT's (26) .…”

Comment on: Gao B, Lu Q, Wan R, Wang Z, Yang Y, Chen Z, Wang Z. “Monthly versus quarterly fremanezumab for the prevention of migraine: a systemic review and meta-analysis from randomized controlled trials”. Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):819–828. Epublished November 2020

“…It is interesting to note that a previously published meta-analysis by the same authors that pooled data from the three phase 3 studies plus two phase 2b studies found no significant differences in mean change in MMD from baseline to week 12 for monthly versus quarterly fremanezumab dosing ( P = 0.86) (Gao et al 2020 ). However, the authors point out in their more recent publication (Gao et al 2021 ) that the results of the prior analysis were based on comparing the two dosage regimens with placebo and did not directly compare the two dosage regimens, hence their rationale for directly comparing quarterly versus monthly dosing in the current analysis.…”