Safety, efficacy, and compliance of moderate-to-high dose eptinezumab and erenumab in chronic migraine patients with medication-overuse headache: an updated systematic review and meta-analysis

Abstract

Background: The use of monoclonal antibodies targeting Calcitonin Gene-Related Peptide (CGRP) is an established treatment for chronic migraine (CM). However, its efficacy in CM patients with medication overuse headache (MOH) remains underexplored, and data on the safety and patient compliance of standard-to-high doses, especially Eptinezumab and Erenumab, over at least three months are limited.

Objective: This study aims to evaluate the efficacy and safety of anti-CGRP therapy (Eptinezumab and Erenumab) in CM and MOH patients. Specifically, it assesses changes in monthly migraine days (MMDs) after 12 weeks, risk of treatment-emergent adverse events (TEAEs) leading to discontinuation, serious TEAEs, common adverse effects, and MOH remission at 6 months.

Methods: A systematic search of PubMed, Cochrane, and Scopus databases identified randomized controlled trials (RCTs) evaluating standard or high dose anti-CGRP therapy in CM patients strictly with MOH. Studies included were required to report a ≥ 50% reduction in MMDs after ≥ 12 weeks, serious TEAEs, TEAEs leading to discontinuation, common adverse events, and MOH remission at 6 months. Heterogeneity was assessed using I² statistics and a random-effects model.

Results: Three RCTs with 769 patients receiving standard-to-high dose anti-CGRP monoclonal antibodies (Eptinezumab and Erenumab) for ≥ 12 weeks were included. Anti-CGRP therapy significantly increased the likelihood of a ≥ 50% reduction in MMDs compared to placebo (OR: 2.43; 95% CI: 1.68-3.51; p < 0.00001). No substantial differences were found in TEAEs leading to discontinuation, nasopharyngitis, upper respiratory tract infections, or serious TEAEs between the anti-CGRP and placebo groups. The likelihood of MOH remission was approximately double in the anti-CGRP group (OR: 1.97; 95% CI: 1.40-2.78; p = 0.0001).

Conclusion: Standard-to-high dose anti-CGRP therapies (eptinezumab, erenumab) effectively reduce monthly migraine days and improve MOH remission rates with minimal adverse effects, showing good tolerability in CM patients with MOH.

Keywords: CM with MOH; Eptinezumab; Erenumab; MOH remission; Tolerability; ≥ 50% reduction in MMDs.

Fig. 1

PRISMA 2020 flow diagram for updated systematic reviews which included searches of databases and registers only

Fig. 2

Safety and Efficacy Outcomes of Eptinezumab and Erenumab (combined standard and high dose therapy). A: At least a 50% reduction in MMDs from baseline with at least 12 weeks of treatment. B: Remission of MOH with at 6 months of treatment. C: Risk of TESAEs. All analyses used a p value < 0.05, with 95% confidence intervals exclude null value of 1 as statistical significant results

Fig. 3

Safety and Efficacy Outcomes of Anti-CGRP Therapy (Eptinezumab 100 mg and Erenumab 70 mg, standard dose therapy). A: At least a 50% reduction in MMDs from baseline with at least 12 weeks of treatment. B: Remission of MOH with at 6 months of treatment. C: Risk of TESAEs. All analyses used a p value < 0.05, with 95% confidence intervals exclude null value of 1 as statistical significant results

Fig. 4

Safety and Efficacy Outcomes of Anti-CGRP Therapy (Eptinezumab 300 mg, Erenumab 140 mg, high dose therapy). A: At least a 50% reduction in MMDs from baseline with at least 12 weeks of treatment. B: Remission of MOH with at 6 months of treatment. C: Risk of TESAEs. All analyses used a p value < 0.05, with 95% confidence intervals exclude null value of 1 as statistical significant results