In a review, researchers outlined the safety and efficacy of erenumab, the only monoclonal antibody built to interact with the calcitonin gene related peptide (CGRP) receptor rather than the CGRP itself, currently indicated as a preventive treatment for migraine.
In a review, researchers outlined the safety and efficacy of erenumab, the only monoclonal antibody (mAb) built to interact with the calcitonin gene related peptide (CGRP) receptor rather than the CGRP itself, currently indicated as a preventive treatment for migraine. The findings were published in Therapeutic Advances in Neurological Disorders.
Erenumab is a fully human antibody, and in 2018, it became the first CGRP mAb class approved by the FDA and European Medicines Agency. The treatment comes in doses of 70 mg and 140 mg and is administered monthly via subcutaneous injection.
“Activation of dural meningeal afferents results in secretion of peptides as pituitary adenylate cyclase activating polypeptide (PACAP), substance P (SP) and CGRP, the latter shown in pre-clinical and clinical experiments to have a pivotal role in migraine pathophysiology,” the researchers explain. Thus, drugs directed at modulating CGRP activity in migraine hold promise as future treatments.
Because erenumab is administered intravenously, it has several benefits compared with oral treatments. Clinical evidence has shown low long-term adherence and persistence to oral migraine-preventive medications, while an injectable self-administered treatment may be more convenient for patients and treating physicians, the authors note.
Erenumab is also associated with a reduced risk of drug-to-drug interactions because it is not eliminated through hepatic, renal, or biliary processes. Lower risk of hepatotoxicity and medication overuse headache (MOH) also contribute to the treatment’s benefits.
According to the researchers, possible sites of action of mAbs relevant to migraine pathophysiology include the trigeminal ganglia, cells containing the CGRP receptor, and trigeminal fibers expressing the CGRP receptor. “Although migraine pathophysiology is no longer thought to involve vasodilation as a disease mechanism, erenumab actions on cerebral and meningeal blood vessels might play some role in the efficacy of this treatment in migraine,” they state.
When it comes to the safety and tolerability of erenumab, the authors point out that across 2 clinical trials, treatment-related adverse events (AEs) were reported in about half of patients receiving 3 monthly injections. However, AEs were rarely the cause of treatment discontinuation and the majority were reported at mild to moderate severity. Common AEs included injection-site pain, upper respiratory tract infections, and influenza.
Erenumab can also “trigger the immune system to produce anti-erenumab antibodies, and there is a possibility that such antibodies could be neutralizing anti-drug antibodies, reducing the efficacy of erenumab,” the authors point out. However, in a small percentage of patients exhibiting neutralizing antibodies in one study, their presence did not result in increased AEs or reduced efficacy of erenumab.
Limited data are available comparing erenumab to other CGRP antagonists, and most data compare the treatment with earlier oral CGRP receptor agonists (gepants). One benefit of erenumab is its prolonged plasma half-life, which allows for longer dosing intervals potentially resulting in higher adherence rates compared with daily dosing.
Several phase 2 and 3 studies have demonstrated the efficacy and safety of erenumab compared with placebo in episodic migraine. For migraineurs with chronic migraine, erenumab was shown to reduce monthly migraine days from baseline. Specifically, “40% of patients in the erenumab 70-mg group and 41% of patients in the erenumab 140-mg group achieved a 50% or more reduction from baseline in monthly migraine days compared with 23% of patients in the placebo arm.” Improvements in quality of life resulting from erenumab treatment have also been reported in trials.
In addition, the treatment is associated with reduced acute migraine-specific medication use, which can lead to reductions in MOH, a common comorbidity among migraineurs.
“Findings from rigorous clinical trials have all pointed towards the clinical efficacy, safety, and good tolerability of erenumab in the prevention of episodic migraine and chronic migraine,” the authors conclude.
However, data presented should be confirmed in the real-world migraine population. “Studies that aim to test the efficacy of anti-CGRP mAbs in patients with migraine and other pain and psychiatric comorbidities will help clarify the role of this class of medications in this complex population.”
Andreou AP, Fuccaro M, Lambru G. The role of erenumab in the treatment of migraine. Ther Adv Neurol Disord. Published online May 27, 2020. doi:10.1177/1756286420927119