Long-term cardiovascular safety and real-world use of eptinezumab - An observational, historical cohort study of patients initiating eptinezumab in routine clinical practice

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  VYEPTI
• Study drug International non-proprietary name (INN) or common name:
  EPTINEZUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (N02CD05) eptinezumab

  eptinezumab
• Medical condition to be studied:
  Migraine

Population studied

• Short description of the study population:
  Patients with migraine, treated with eptinezumab or other preventive migraine medications
• Special population of interest:
  Other
• Special population of interest, other:
  Migraine
• Estimated number of subjects:
  28394

Study design details

• Main study objective:
  To assess the long-term cardiovascular risk in migraine patients treated with eptinezumab, in comparison to appropriate control cohorts of patients with migraine who were not treated with eptinezumab. To evaluate the long-term cardiovascular risk in migraine patients with a known history of cardiovascular disease using eptinezumab in comparison to migraine patients with a known history of cardiovascular disease not using eptinezumab.
• Setting:
  The study will include migraine patients treated with eptinezumab in routine clinical practice and followed-up for a maximum of six years from exposure start. The following control cohorts will be identified: 1. A cohort of migraine patients treated with non-CGRP targeting preventive migraine medications; 2. a cohort of migraine patients not treated with any preventive migraine medication; and 3. a cohort of migraine patients representing standard-of-care. The study inclusion period will be from eptinezumab launch date in the respective country until 31 December 2026.
• Comparators:
  1. non-GCRP preventive migraine medications; 2. no exposure to preventive migraine medications; 3. migraine standard-of-care
• Outcomes:
  Primary outcome: major adverse cardiovascular events (MACE), defined as nonfatal stroke, nonfatal acute coronary syndrome, or cardiovascular death. Secondary outcomes: non-fatal stroke; stroke; ischemic stroke; non-fatal ACS; ACS; CV death; transitory ischemic attack (TIA); angina pectoris (all subtypes, i.e. independently from coding of stable/instable); percutaneous coronary intervention (PCI); heart failure.
• Data analysis plan:
  After identification of the study cohorts, cohort balancing (i.e. identification of appropriate control cohorts) will be performed within a propensity score-based approach. Study analyses will be done in the sequence of ‘cohort balancing’ followed by the ‘cohort analyses’ in the unbalanced and balanced cohorts. Hazard ratios of the primary and secondary study outcomes, along with their 95% confidence intervals, will be estimated to assess the long-term cardiovascular risk in patients treated with eptinezumab, in comparison to each control cohort. For each of the three comparisons (EE vs. MEC; EE vs. MNEC; EE vs. SoC), hazard ratios will be estimated for the unbalanced and the balanced study cohorts using COX proportional hazard regression analysis. In addition, cumulative incidences will be estimated for the unbalanced and balanced cohorts. Subgroup analyses will be performed to evaluate the impact of a known history of cardiovascular diseases on the long-term cardiovascular risk in patients using eptinezumab in clinical practice, as well as the impact of migraine disease severity.