What is the recommended dosing regimen and treatment approach for eptinezumab (Eptinezumab) in patients with migraine who have not responded to other preventive treatments?

Eptinezumab Dosing and Treatment Approach for Migraine Prevention

For patients with migraine who have failed other preventive treatments, initiate eptinezumab 100 mg IV every 3 months, with assessment of efficacy only after 3-6 months of treatment, and consider dose escalation to 300 mg if response is inadequate after the second infusion. 1, 2, 3

FDA-Approved Dosing Regimen

• Standard starting dose: 100 mg IV infusion over 30 minutes every 12 weeks 3
• Alternative dose: 300 mg IV infusion every 12 weeks for patients who may benefit from higher dosing 3
• Dilute in 100 mL of 0.9% Sodium Chloride Injection using PVC, PE, or PO infusion bags 3
• Use 0.2 or 0.22 micron in-line sterile filter during administration 3
• Flush line with 20 mL normal saline after infusion completion 3

Position in Treatment Algorithm

Eptinezumab is positioned as third-line therapy after failure of first-line agents (beta-blockers, topiramate, candesartan) and second-line agents (flunarizine, amitriptyline, valproate in men). 1, 2 In Europe, regulatory restrictions specifically limit CGRP monoclonal antibodies to patients in whom other preventive drugs have failed or are contraindicated 1.

Critical Timeline for Efficacy Assessment

• Do not assess treatment failure before 3-6 months (2-3 infusions) of therapy 1, 2
• Efficacy rarely manifests immediately and requires several weeks to months to ascertain 1
• Patients should be discouraged from abandoning treatment during early stages based on apparent inefficacy 1
• Primary efficacy endpoints are measured at 12 weeks, with responder rates often increasing after the second infusion 4, 5

Response Patterns and Dose Escalation Strategy

Among initial non-responders during weeks 1-12, approximately 30-35% become responders after their second infusion, demonstrating that treatment response develops or increases with subsequent dosing. 4, 5

• ≥30% responder rates increase from 65.9% to 70.4% (100 mg dose) and 71.0% to 74.5% (300 mg dose) between weeks 1-12 and weeks 13-24 5
• The largest increase in responder rates occurs after the second infusion 5
• Consider dose escalation from 100 mg to 300 mg at week 12 for patients with suboptimal response 4, 6
• In real-world practice, approximately one-third of patients escalate to 300 mg at week 12 and achieve further significant reductions in migraine-related disability 4

Quantifying Treatment Success

Calculate the percentage reduction in monthly migraine days or monthly headache days of moderate-to-severe intensity to quantify preventive treatment success. 1

• ≥30% reduction in monthly migraine days is a clinically meaningful threshold 4, 5
• ≥50% reduction represents robust response 1, 5
• ≥75% reduction indicates excellent response 1, 5

Duration of Therapy and Pausing Considerations

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 1, 2
• The purpose of pausing is to minimize unnecessary drug exposure and allow some patients to manage migraine with acute medications only 1
• Sustained efficacy has been demonstrated through at least 2 years of continuous treatment 7, 8

Safety Profile and Hypersensitivity Monitoring

Hypersensitivity reactions, including anaphylaxis and angioedema, can occur during infusion and may require discontinuation. 3

• Most hypersensitivity reactions occur during infusion and are not serious but often lead to discontinuation 3
• Treatment-emergent adverse events reported by ≥2% of patients include nasopharyngitis, upper respiratory tract infection, and fatigue 7
• If hypersensitivity reaction occurs, consider discontinuing eptinezumab and institute appropriate therapy 3
• Eptinezumab is contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or any excipients 3

Critical Pitfalls to Avoid

• Abandoning treatment before 3-6 months (minimum 2 infusions) based on perceived lack of efficacy 1, 2, 4
• Failing to recognize that approximately one-third of initial non-responders become responders after the second dose 4, 5
• Not addressing medication overuse headache, which can interfere with preventive treatment effectiveness 2, 4
• Failing to monitor for hypersensitivity reactions during the 30-minute infusion period 3

Special Considerations for Treatment-Refractory Patients

For patients who have failed subcutaneous CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab), eptinezumab may still provide benefit as failure of one preventive treatment does not predict failure of other drug classes. 1, 4, 6

• In therapy-refractory patients who failed erenumab and at least one other CGRP mAb, 23.1% achieved ≥30% reduction in monthly migraine days at week 12, increasing to 29.7% at week 24 6
• 38.5% reported clinically meaningful reduction in HIT-6 scores and 52.4% in MIDAS scores during weeks 21-24 6
• The intravenous route and different binding characteristics may explain efficacy in some patients unresponsive to subcutaneous formulations 6

Infrastructure Requirements

Eptinezumab requires healthcare infrastructure for IV administration and patient time commitment (approximately 30 minutes for infusion plus observation time). 4 This logistical consideration distinguishes it from subcutaneous CGRP monoclonal antibodies that patients can self-administer at home 4.