Review: Biologic Migraine Therapies Demonstrate Safety, Tolerability

The relatively new biologic therapies for migraine demonstrated low immunogenicity rates and rare adverse events, according to the results of a new review.

“Taken together, these results add to the growing body of evidence for the safety and tolerability of this class of migraine medications,” wrote the authors of a recent review published in the Journal of Headache and Pain.¹

Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been shown to be effective in migraine prevention. Specifically, the authors reviewed safety data on eptinezumab (Vyepti), erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality).

Among clinical studies of eptinezumab, erenumab, fremanezumab, and galcanezumab, reported rates of patients developing anti-drug antibodies (ADAs) and neutralizing ADAs (NAbs) were lowest in the fremanezumab studies, whereas eptinezumab had the highest reported rates of ADAs and NAbs.

“This observation is noteworthy given that eptinezumab is administered intravenously, whereas erenumab, fremanezumab, and galcanezumab are administered by subcutaneous injection,” the authors wrote.

Still, results from clinical trials among patients receiving CGRP mAbs for migraine prevention have demonstrated that treatments are generally well tolerated and effective. The prevalence of ADAs among CGRP mAb clinical trials range from < 1% to ~ 18%, depending on patient population, biologic therapy, and treatment paradigm.

NAbs were slightly less common, with a prevalence ranging from 0 to 12%. “While immunogenicity rates were low, available evidence shows that immunogenicity-related adverse events (AEs) were rare, thus underscoring the safety of CGRP mAbs, the authors wrote.

Currently available data on immunogenicity profiles do not demonstrate an impact of ADA development on the efficacy or safety of CGRP mAbs. However, ongoing trials and upcoming studies can provide additional information about immunogenicity, the authors noted.

“Indeed, there are questions about the impact of NAbs and ADAs on mAb efficacy over the long-term, especially whether loss of drug efficacy is associated with an increase in ADA titer over time,” the authors wrote. “There are also questions about long-term safety concerns in patients developing ADAs, particularly with respect to instances where immune complexes form and whether they lead to cytokine activation, precipitate out and deposit in tissues, and lead to additional tissue injury (nephropathy/nephritis).”

“Additional data could help to understand the long-term impacts of immunogenicity on CGRP mAb efficacy and safety,” they added.

Reference:

1. Cohen, JM, Ning X, Kessler Y, et al. Immunogenicity of biologic therapies for migraine: a review of current evidence. The Journal of Headache and Pain. January 7, 2021. https://doi.org/10.1186/s10194-020-01211-5