Pan European Prospective Observational Study of Fremanezumab effectiveness in patients with chronic or episodic migraine in the Real-World: PEARL study

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

  Evaluation of patient-reported outcomes

  Safety study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Prospective observational study in real-world clinical practice

Study drug and medical condition

• Medicinal product name:
  AJOVY

  MIGRAINE RELIEF
• Study drug International non-proprietary name (INN) or common name:
  FREMANEZUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (N02CD03) fremanezumab

  fremanezumab
• Medical condition to be studied:
  Migraine
• Additional medical condition(s):
  Chronic migraine (CM) and Episodic migraine (EM)

Population studied

• Short description of the study population:
  The study population was composed of male and female patients, aged 18 years and older, diagnosed with CM or EM, and had been prescribed fremanezumab according to the SmPC as a treatment decision of their physician before enrollment in this study. ; Patients included might have received acute or other preventive migraine treatments before the start of this study and might have continued these treatments, changed or unchanged, throughout the study period. ; Up to 30% of patients enrolled were allowed to have previously taken preventive migraine treatment with other monoclonal antibodies targeting the CGRP pathway. ; Patients who switched from another monoclonal antibody targeting the CGRP pathway were recommended to wait until their next scheduled dose before starting fremanezumab. The number of actually enrolled subjects was 1140 patients.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  1140

Study design details

• Study design:
  This was a 45-month (21-month recruitment and 24-month follow-up), multicenter, multicounty (pan-European), prospective observational study to describe evidence of outcomes of fremanezumab treatment according to the Summary of Product Characteristics (SmPC) in real-world clinical practice.
• Main study objective:
  To evaluate the effectiveness of fremanezumab in adult patients with CM or EM who have at least 4 migraine days per month, including a proportion of patients reaching a 50% reduction in the monthly average number of migraine days during a 6 month period after the first dose of fremanezumab, in real world clinical practice
• Setting:
  The study took place between 07/08/2020 and 17/04/2024 in 11 European countries. ; Patients were included in the study if all of the following inclusion criteria were fulfilled:; a. The patient has signed the informed consent. ; b. The patient is male or female and 18 years of age or older. ; c. The patient has a diagnosis of CM or EM. ; d. The patient has been prescribed fremanezumab as a treatment decision of their physician according to the SmPC and their first dose of fremanezumab was within 3 months (+ 7 days) of the day of enrollment. ; e. The patient has been maintaining a daily headache diary as part of their routine disease management per their treating physician and has maintained a headache diary for at least 21 days in the 28 days prior to fremanezumab treatment initiation. ; f. For patients with fremanezumab treatment initiation at least 28 days before enrollment, the patient has maintained a headache diary for at least 21 days per month since fremanezumab treatment initiation. ; g. The patient’s headache diary ideally captures information on headache duration, headache severity, and headache characteristics. ; h. The patient understands and is willing to keep records in their electronic or paper headache diary for the course of the study. ; ; Exclusion Criteria ; Patients were excluded from the study for any of the following reasons:; a. The patient is not treated according to the SmPC. ; b. Up to 30% of patients enrolled may have previously taken preventive migraine treatment with other monoclonal antibodies targeting the CGRP pathway. ; c. The patient is participating in an interventional clinical trial in EM or CM
• Comparators:
  Not applicable
• Outcomes:
  Primary objective: ; • To evaluate the effectiveness of fremanezumab administered in adult patients with chronic migraine (CM) or episodic migraine (EM) who have at least 4 migraine days per month, including the proportion of patients reaching at least 50% reduction in the monthly average number of migraine days during the 6-month period after the first dose of fremanezumab, in real-world clinical practice. ; Secondary objectives:; • To evaluate measures of effectiveness of fremanezumab, including monthly average number of migraine days, and disability scores, in real-world clinical practice; • To evaluate the use of concomitant acute migraine medications in real-world clinical practice; • To evaluate patient adherence to and persistence with fremanezumab treatment in real-world clinical practice; • To evaluate measures of effectiveness of fremanezumab in real-world clinical practice in patients who have no prior exposure to a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) pathway ; Exploratory objectives:; • To evaluate the impact of fremanezumab on reducing migraine severity in real-world clinical practice; • To assess the number and classes of concomitant preventive and acute migraine medications used in real-world clinical practice; • To evaluate outcomes following fremanezumab cessation and any subsequent reinitiation of fremanezumab treatment in real-world clinical practice; • To evaluate the reasons for fremanezumab cessation and reinitiation in real-world clinical practice; • To evaluate measures of effectiveness of fremanezumab in real-world clinical practice in patients who have prior exposure to a monoclonal antibody targeting the CGRP pathway
• Data analysis plan:
  All variables will be summarized descriptively. For continuous variables, descriptive statistics (n, mean, standard deviation, standard error of mean, median, minimum, and maximum) will be provided for actual values and changes from baseline to each visit. For categorical variables, frequency and percentage will be provided. ; The 95% confidence intervals will be provided for point estimate, if appropriate. Nominal p-values for comparisons to baseline or for testing some other hypotheses may be provided as well. ; This approach will apply to all interim analyses and the final analysis. Data analyses will be performed based on the data available from individual patient diaries. Data from monthly and quarterly fremanezumab dosing groups will be combined for all analyses. ; Analyses of monthly and quarterly fremanezumab dosing subgroups and for EM and CM subgroups will be also provided. Analyses for patients who do not miss any doses up to a certain timepoint will be also provided