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 13th 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 (MMDRes). 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-MMDRes (MMDRes: T0: 23.0 +/- 4.5 vs. T13: 6.6 +/- 4.8; NON-MMDRes: 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 MMDRes group (83.3%) when compared to NON-MMDRes (42.9%) (p= 0.001). MMDRes 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 MMDRes" 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.