Predictive Role of MIDAS Reduction at 3 Months for Erenumab Treatment (Ere-MIDAS)

June 28, 2022 updated by: IRCCS National Neurological Institute "C. Mondino" Foundation

Study of Early MIDAS Reduction at 3 Months as Predictor of Long-term Erenumab Treatment in Chronic Migraine: a Real-life, Open-label, Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Observational

Enrollment (Actual)

53

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Headache Science & Neurorehabilitation Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with chronic migraine with clinical features in agreement with AIFA regulations for CGRP-mAbs prescription.

Description

Inclusion Criteria:

  • diagnosis of CM according to ICHD-3 criteria for at least 12 months prior to enrollment;
  • completion of a full headache diary in the 3 months preceding the enrollment; compliance to complete a daily headache diary for 1 year;
  • previous failure of at least 3 classes of preventive treatments among beta-blockers, antiepileptic drugs, antidepressants, or onabotulinumtoxin-A;
  • MIDAS score > 11.

Exclusion Criteria:

  • severe cardiologic comorbidities;
  • pregnancy and breastfeeding;
  • previous adverse reaction to latex

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predictive role of early MIDAS score reduction
Time Frame: Reduction in MMDs across 1-year treatment period
To evaluate whether a >50% reduction in the MIDAS score at T3 (MIDAS-Res) is predictive of a more pronounced reduction in MMDs during a 1-year erenumab treatment.
Reduction in MMDs across 1-year treatment period
Predictive role of early MMDs score reduction
Time Frame: Reduction in MMDs across 1-year treatment period
To evaluate whether a >50% reduction in the monthly migraine days (MMDs) at T3 (MMD-Res) is predictive of a more pronounced reduction in MMDs during a 1-year erenumab treatment.
Reduction in MMDs across 1-year treatment period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between MIDAS-Res or MMD-Res and Responders at the end of the 1-year erenumab treatment
Time Frame: MIDAS-Res and MMD-Res defined after three months of erenumab treatment. ResponderT13 defined in the last 4 weeks of the 1-year erenumab treatment.
Association between MIDAS-Res or MMD-Res 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).
MIDAS-Res and MMD-Res defined after three months of erenumab treatment. ResponderT13 defined in the last 4 weeks of the 1-year erenumab treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS National Neurological Institute "C. Mondino" Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2018

Primary Completion (Actual)

January 1, 2020

Study Completion (Actual)

January 1, 2021

Study Registration Dates

First Submitted

June 28, 2022

First Submitted That Met QC Criteria

June 28, 2022

First Posted (Actual)

July 1, 2022

Study Record Updates

Last Update Posted (Actual)

July 1, 2022

Last Update Submitted That Met QC Criteria

June 28, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ERENUMAB2022

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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