Does MIDAS reduction at 3 months predict the outcome of erenumab treatment? A real-world, open-label trial.

Background: In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) score ≥ 11. Eligibility to treatment continuation requires a ≥ 50% MIDAS score reduction at three months (T3). In this study, we evaluate whether a ≥ 50% MIDAS score reduction at T3 is a reliable predictor of response to one-year erenumab treatment.

Methods: In this prospective, open-label, real-world study, 77 CM patients were treated with erenumab 70-140 mg s.c. every 28 days for one year (T13). We collected the following variables: monthly migraine days (MMDs), monthly headache days (MHDs), days of acute medication intake, MIDAS, HIT-6, anxiety, depression, quality of life and allodynia. Response to erenumab was evaluated as: i) average reduction in MMDs during the 1-year treatment period; and ii) percentage of patients with ≥ 50% reduction in MMDs during the last 4 weeks after the 13^th injection (Responders^T13).

Results: Erenumab induced a sustained reduction in MMDs, MHDs and intake of acute medications across the 12-month treatment period, with 64.9% of patients qualifying as Responders^T13. At T3, 55.8% of patients reported a ≥ 50% reduction in MIDAS score (MIDAS^Res) and 55.4% of patients reported a ≥ 50% reduction in MMDs (MMD^Res). MIDAS^Res and MMD^Res patients showed a more pronounced reduction in MMDs during the 1-year treatment as compared to NON-MIDAS^Res (MIDAS^Res: T0: 23.5 ± 4.9 vs. T13: 7.7 ± 6.2; NON- MIDAS^Res: T0: 21.6 ± 5.4 vs. T13: 11.3 ± 8.8, p = 0.045) and NON-MMD^Res (MMD^Res: T0: 23.0 ± 4.5 vs. T13: 6.6 ± 4.8; NON-MMD^Res: T0: 22.3 ± 6.0 vs. T13: 12.7 ± 9.2, p < 0.001) groups. The percentage of Responders^T13 did not differ between MIDAS^Res (74.4%) and NON-MIDAS^Res (52.9%) patients (p = 0.058), while the percentage of Responders^T13 was higher in the MMD^Res group (83.3%) when compared to NON-MMD^Res (42.9%) (p = 0.001). MMD^Res predicted the long-term outcome according to a multivariate analysis (Exp(B) = 7.128; p = 0.001), while MIDAS^Res did not. Treatment discontinuation based on MIDAS^Res would have early excluded 36.0% of Responders^T13. Discontinuation based on "either MIDAS^Res or MMD^Res" would have excluded a lower percentage (16%) of Responders^T13.

Conclusion: MIDAS^Res only partly reflects the 12-month outcome of erenumab treatment in CM, as it excludes more than one third of responders. A criterion based on the alternative consideration of ≥ 50% reduction in MIDAS score or MMDs in the first three months of treatment represents a more precise and inclusive option.

Trial registration: The trial was retrospectively registered at www.

Clinicaltrials: gov (NCT05442008). CGRP: Calcitonin Gene Related Peptide.

Midas: MIgraine Disability Assessment. MMDs: monthly migraine days. MIDAS^Res: Patients with a MIDAS score reduction of at least 50% at T3. MMD^Res: Patients with a MMDs reduction of at least 50% at T3. Responder^T13: Patients with a MMDs reduction from baseline of at least 50% in the last 4 weeks of observation period (after 13 erenumab administrations). T0: First erenumab administration. T3, T6, T9, T12: Follow-up visits at three, six, nine, and twelve months after first erenumab administration. T13: Last visit of the protocol.