Erenumab

Erenumab is a human monoclonal antibody used for the preventive treatment of migraine in adults. It belongs to the class of calcitonin gene-related peptide receptor antagonists and works by binding to the CGRP receptor and blocking the activity of CGRP, a signaling molecule involved in migraine mechanisms. By preventing CGRP from activating its receptor, erenumab can reduce the frequency of migraine attacks and related symptoms. Erenumab is administered by subcutaneous injection and is available in prefilled syringes and autoinjector devices in approved strengths. It may be used for patients with episodic or chronic migraine depending on the applicable regulatory indication and clinical assessment. Clinical studies including STRIVE, ARISE, and LIBERTY demonstrated reductions in monthly migraine days in adults receiving erenumab compared with placebo, including patients who had previously experienced difficulties with other preventive treatments. Erenumab is designed for preventive treatment rather than immediate relief of an acute migraine attack. Its long duration of action permits once-monthly administration, which can be useful when a regular preventive treatment strategy is clinically appropriate.

Erenumab was developed as a targeted monoclonal antibody designed to interfere with CGRP signaling by binding to the CGRP receptor. The U.S. Food and Drug Administration granted its initial approval in 2018 for the preventive treatment of migraine in adults. The European Medicines Agency issued European Union marketing authorization for Aimovig on 26 July 2018 for migraine prophylaxis in adults with at least 4 migraine days per month when treatment is initiated. The FDA prescribing information identifies erenumab as a CGRP receptor antagonist and includes preventive treatment of migraine in adults as its indication. Major clinical development programs included randomized phase III studies in episodic and chronic migraine, including STRIVE, ARISE, and studies evaluating patients with previous preventive-treatment failures such as LIBERTY. Long-term follow-up studies have also evaluated sustained efficacy and safety during continued monthly treatment.

Erenumab is indicated for the preventive treatment of migraine in adults. In the United States, the approved indication covers preventive treatment of migraine in adults without limiting use to a particular migraine frequency in the prescribing information. In the European Union, erenumab is indicated for migraine prophylaxis in adults who have at least 4 migraine days per month when treatment is initiated. Clinical studies have evaluated both episodic migraine and chronic migraine populations, as well as patients who had not responded adequately to or could not tolerate several previous preventive treatments. Erenumab is intended for prevention and is not a treatment for immediately stopping an established acute migraine attack. The decision to initiate treatment, select the dose, and continue therapy should be based on migraine frequency, treatment response, tolerability, previous preventive therapies, and applicable regulatory guidance.

Erenumab is administered by subcutaneous injection, generally once every month. The recommended U.S. dose is 70 mg once monthly, although some patients may benefit from 140 mg once monthly. Depending on the formulation, the dose may be administered using a single prefilled syringe or autoinjector, with appropriate patient or caregiver training for self-administration. Injection sites include the abdomen, thigh, or upper arm, and injections should not be given into areas that are tender, bruised, red, or hardened. If a dose is missed, it should be administered as soon as possible and the monthly schedule continued from the date of the last dose. Treatment duration depends on clinical response, tolerability, migraine burden, and the treating clinician's assessment. Patients should be periodically reviewed to determine whether continued preventive therapy remains appropriate.

Common side effects of erenumab include injection-site reactions and constipation. Injection-site reactions may include pain, redness, or itching at the injection site. Muscle cramps or spasms may also occur. Some patients may experience other symptoms reported during postmarketing use, such as rash or hair loss, although the frequency of these reactions is not always established. Most adverse effects reported in clinical studies were manageable, but individual responses can vary. Patients should inform their healthcare professional about persistent or troublesome constipation, significant skin reactions, or other new symptoms occurring during treatment so that appropriate assessment and management can be provided.

Important safety concerns with erenumab include serious hypersensitivity reactions, constipation with potentially serious complications, new-onset or worsening hypertension, and new or worsening Raynaud's phenomenon. Hypersensitivity reactions can include rash, angioedema, and anaphylaxis and may occur within hours of administration or, in some cases, more than one week after treatment. Severe constipation has occasionally required hospitalization or surgical treatment, particularly when associated with reduced gastrointestinal motility. Blood pressure should be monitored when clinically appropriate because hypertension or worsening of existing hypertension has been reported after treatment. Patients with a history of Raynaud's phenomenon should be monitored for recurrence or worsening of symptoms, and treatment should be discontinued if clinically significant Raynaud's phenomenon develops according to applicable prescribing information.

Before starting erenumab, clinicians should review migraine history, previous preventive treatments, cardiovascular and vascular history, blood pressure, bowel habits, history of hypersensitivity reactions, and current medicines. Patients with pre-existing hypertension or Raynaud's phenomenon may require closer monitoring. Erenumab is not metabolized by cytochrome P450 enzymes, so conventional CYP-mediated drug interactions are generally unlikely. Clinical studies have not identified a meaningful pharmacokinetic interaction with sumatriptan or combined oral contraceptives. Medicines that reduce gastrointestinal motility may increase the risk of more severe constipation and should be considered when reviewing concomitant therapy. Pregnancy and breastfeeding decisions should be individualized because available human data remain limited. Pediatric safety and effectiveness have not been established in the current U.S. prescribing information.

Before prescribing, confirm the migraine diagnosis and establish baseline migraine frequency and treatment goals so that response can be assessed over time. Review previous preventive therapies, blood pressure, bowel function, vascular symptoms, and relevant concomitant medicines. Patients using self-injection should receive appropriate training on aseptic technique, device operation, injection-site selection, storage, and safe handling. The medicine should be allowed to reach room temperature before administration according to the approved product instructions and should not be shaken or exposed to direct heat. Pharmacists should verify the prescribed monthly dose, formulation, storage conditions, and patient understanding of administration. During follow-up, assess migraine frequency, treatment response, constipation, blood pressure, injection-site reactions, hypersensitivity symptoms, and symptoms suggestive of Raynaud's phenomenon. Continued treatment should be reviewed periodically according to clinical response and tolerability.