Predictive Role of MIDAS Reduction at 3 Months for Erenumab Treatment
Condition: Migraine
MeSH terms: Migraine Disorders
Study type: Observational

Summary: 
      In 2021, the Italian Medicines Agency approved reimbursement of monoclonal antibodies
      targeting the CGRP pathway (CGRP-mAbs) as preventive therapies for patients with high
      frequency and chronic migraine (CM). A moderate to severe disability, quantified as a
      MIgraine Disability ASsessment (MIDAS) score > or equal to 11, is required for prescription.
      Score reduction of at least 50% after the first three months (T3) is mandatory to continue
      treatment.

      This is a prospective real-life, open-label study. CM patients will be treated with erenumab
      70-140 mg subcutaneous injections every 28 days for one year (T13). We will record the
      following parameters: demographic and headache features, monthly migraine and headache days
      (MMDs and MHDs respectively), days and doses of symptomatic intake. Patients also completed
      questionnaires evaluating migraine related disability (MIDAS and HIT-6), psychological
      comorbidities (HADS-A and HADS-D), quality of life (MSQ and 0 to 100 visual analogue scale)
      and allodynia (ASC-12).

      At least a 50% reduction in MIDAS score or MMDs after 3 months of treatment will be testedas
      predictors of long-term clinical outcome.
    

Detailed description: 
      Monoclonal antibodies directed against the Calcitonin Gene Related Peptide (CGRP-mAbs)
      pathway are a silver lining in the setting of migraine therapies, partly overcoming the
      issues related to poor effectiveness and tolerability of previous preventive treatments.

      These drugs act on the CGRP pathway, a key vasoactive neuropeptide in migraine
      pathophysiology involved in activation and sensitization of afferent trigeminal nociceptors
      of the trigeminovascular system. Galcanezumab, fremanezumab and eptinezumab target the CGRP
      ligand, while erenumab, a fully human IgG2, targets its receptor. mAbs efficacy and safety
      have been largely documented in multiple randomized clinical trials, open-label studies as
      well as in the real-world setting.

      The Italian Medicines Agency (AIFA) approved a 12-month period of mAbs treatment
      reimbursement through the National Health Service for migraine patients with the following
      features: i) at least 8 migraine days per month in the last three months, ii) a MIgraine
      Disability ASsessment (MIDAS) score ≥ 11, and iii) previous failure for inefficacy or no
      tolerability of at least three preventive drugs, among β-blockers, tricyclic antidepressants,
      antiepileptics, and onabotulinumtoxin-A for chronic migraine (CM).

      In addition, a reduction of at least 50% of MIDAS score after 3 and 6 months of treatment is
      the only mandatory step to continue beyond these check-points. Thus, MIDAS score is pivotal
      for mAbs treatment initiation and continuation. MIDAS is a self-administered five-item
      questionnaire focusing on reduction in home and workplace productivity, and a score > 11
      identify a set of patients with a moderate to severe disability. A MIDAS score reduction
      during mAbs treatment was demonstrated in the short and long term period, but its role as
      predictor of mAbs clinical outcome has never been consistently studied. A major concern for
      using a single parameter as a mandatory criterion for prescription and continuation of a
      preventive treatment is the limited ability to capture the multifaced disability that
      characterize the migraine spectrum. On the other side, reduction in monthly migraine days
      (MMDs) represents a pivotal outcome for clinical trials and physicians, but this may not
      completely highlight the patients' perspective.

      The investigators consecutively screened migraine patients attending the outpatient clinic of
      the Headache Science & Neurorehabilitation Center of the IRCCS Mondino Foundation (Pavia,
      Italy).

      The patients underwent a 1-year treatment with erenumab subcutaneous administration every 28
      days (13 administrations) outside of the AIFA reimbursement program within a compassionate
      program.

      During a baseline visit (T0), a neurologist with expertise in the headache field provided
      clinical indication to erenumab. At T0, the investigators checked the inclusion/exclusion
      criteria and the headache diaries of the three preceding months, and performed a full
      neurologic and general examination and a thorough anamnestic evaluation.

      Patients who agreed to participate in the study signed a written informed consent and
      completed the baseline procedures, including clinical and demographic data recording and
      completion of a set of questionnaires to assess migraine related disability (MIDAS and
      HIT-6), psychological comorbidities (HADS-A and HADS-D), quality of life (MSQ), a
      self-perception of general health (0 to 100 visual analogue scale), and allodynia (ASC-12).

      The first erenumab administration (70 mg) was delivered in the hospital setting at T0. After
      the first administration the patients were observed for 2 hours to monitor possible acute
      adverse events. The patients were then instructed to perform the following
      self-administrations of erenumab at home every 28 days (T1 to T12).

      The patients returned to the Center every 12 weeks for the follow-up visits (T3 - T6 - T9 -
      T12), and at T13 for the last visit of the protocol. Monthly headache days (MHDs), monthly
      migraine days (MMDs), and days of acute drug intake were prospectively recorded in a paper
      headache diary. At each follow-up visit, the patients completed the same study procedures and
      clinical scales previously defined. At T3, erenumab dosage was increased in 72 patients up to
      140 mg, according to the physician's judgment. All patients were allowed to keep their oral
      preventive medication with a stable dose across all study period.

      The primary outcome was to evaluate the role of MIDAS reduction of at least 50% at T3
      (MIDASRes) as a predictor of the long-term clinical outcome. As co-primary outcome, the
      investigators explored the role of early (T3) 50% MMDs reduction (MMDRes) as predictor of
      long-term efficacy.

      In addition, the investigators evaluated the association between MIDASRes as well as MMDRes
      and the percentage of patients with a reduction in MMDs of at least 50% in the last 4 weeks
      of observation period (T13) when compared to baseline (RespondersT13). ResponderT13 were
      defined according to the IHS Guidelines for clinical trials involving CM patients.

      As secondary outcomes, the investigators searched for possible associations between baseline
      clinical/demographic features and long-term efficacy of erenumab treatment, while, as
      exploratory outcomes, we described 1-year change in migraine-related disability, anxiety and
      depression severity, allodynia, and quality of life. The study was approved by the local
      Ethics Committee (P-20190105434).
    

Intervention name(s): Erenumab 70/140 mg s.c.
Intervention type(s): Drug
Intervention description(s): Monoclonal antibody directed against the receptor of the Calcitonin Gene Related Peptide (CGRP)
Intervention MeSH terms: Erenumab
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with chronic migraine with clinical features in agreement with AIFA regulations
        for CGRP-mAbs prescription.
      
Keywords: Migraine; Headache; CGRP; Monoclonal antibodies; Pain; Chronic migraine