Long-Term Effectiveness of Three Anti-CGRP Monoclonal Antibodies in Resistant Chronic Migraine Patients Based on the MIDAS score

Abstract

Background: Criteria, including clinical features and effective outcomes, for access and persistence of novel but costly treatments may vary between countries, thus affecting the health of patients. Monoclonal antibodies against the calcitonin gene-related peptide pathway (anti-CGRP mAbs) for migraine treatment are currently prescribed following strict criteria.

Objective: The aim was to assess the effectiveness and safety of three anti-CGRP mAbs (erenumab, galcanezumab, and fremanezumab) in consecutive resistant chronic migraine patients presenting at our Headache Center and the impact of criteria set by the Italian Medicines Agency to start and continue (achieving a ≥ 50% reduction in Migraine Disability Assessment [MIDAS] score) with treatment under the reimbursement program.

Methods: A monocentric, prospective, cohort study was conducted, enrolling 203 severe (resistant to three or more preventive treatments) chronic migraine patients (84.7% with medication overuse) treated with erenumab (47.2%), galcanezumab (36.5%), or fremanezumab (16.3%), with up to 12 months follow-up. Patients completed a headache diary that included monthly migraine days (MMDs), number of analgesics and days with analgesic use, and patient-reported outcome questionnaires (MIDAS, Headache Impact Test 6 [HIT-6] questionnaires, and the Patient Global Impression of Change [PGIC] scale). Moreover, percentages of patients showing ≥ 50%, ≥ 75% and 100% reduction in MMDs (responder rates) were calculated at different follow-ups. A subgroup analysis was performed for patients with 12-month follow-up. Potential predictors of response were assessed at different follow-ups.

Results: In the overall population, all three anti-CGRP mAbs were similarly effective and dropouts were 17.2%. The percentage of patients with ≥ 50% reduction in MMDs (min-max 36.4-56.8%) and in monthly analgesic consumption (51.1-75.7%) was inferior to the percentage of patients who reported a ≥ 50% reduction in MIDAS score (89.5-100%). HIT-6 score was also consistently reduced at all follow-ups. In patients with a 12-month follow-up, MIDAS and HIT-6 scores were also reduced at all follow-ups compared with baseline, with 84.4-100% of patients achieving a ≥ 50% reduction in MIDAS score, and patients with a ≥ 50% response rate ranging from 36.4 to 66.6%. No severe adverse events were recorded. Fewer migraine days at baseline were associated with ≥ 50% response rate at 1 month and fewer MMDs, years of chronic migraine, and monthly analgesic use at 6 months.

Conclusion: In resistant chronic migraine patients, anti-CGRP mAbs are effective and safe. A ≥ 50% reduction in MIDAS score seems to be the most advantageous outcome measure in this setting, which allows most severe migraine patients to persist with treatment.

Conflict of interest statement

PG received personal fees from Allergan, Eli Lilly, Novartis, Amgen, and TEVA and grants from Amgen, TEVA, Eli-Lilly, Allergan, and Chiesi; was involved in the Scientific Advisory Board, Endosome Therapeutics; and is the founding scientist of FloNext srl, Spinoff of the University of Florence. FDC received personal fees from TEVA, Eli Lilly, and Novartis. LFI, DF, SB, and AC declare no conflicting interests.

© 2022. The Author(s).

Figures

Figure 1.

Patient distribution flow-chart in effectiveness and safety analysis. AE adverse event

Figure 2.

Migraine Disability Assessment (MIDAS) questionnaire total scores (A) and number [percentage] of patients who persisted with treatment based on ≥ 50% reduction in MIDAS score (B) during treatment follow-up. Error bars represent 95% confidence intervals. Number in square represents mean reduction compared to baseline within the group for each follow-up (A) or percentage of patients (B) per group

Figure 3.

A Monthly migraine days (MMDs) frequency during anti-CGRP treatment in patients with at least 1-month follow-up and migraine days at each follow-up and MMD reduction compared to baseline. B Number of analgesics used and days with at least one analgesic used per month and their reduction compared to baseline. Error bars represent 95% confidence intervals. Analgesics include NSAIDs, triptans, analgesic associations (with or without opioids), opioids, and ergot derivative. CGRP calcitonin gene-related peptide, NSAID nonsteroidal anti-inflammatory drug

Figure 4.

A Effectiveness analysis of response rate ≥ 50%, ≥ 75%, and 100% in all patients; B in patients that completed 12 months of treatment; and C in patients with 12-month follow-up