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). GRAPHICAL ABSTRACT: 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. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10194-022-01480-2.