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

Abstract

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 (RespondersT13).

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 RespondersT13. At T3, 55.8% of patients reported a ≥ 50% reduction in MIDAS score (MIDASRes) and 55.4% of patients reported a ≥ 50% reduction in MMDs (MMDRes). MIDASRes and MMDRes patients showed a more pronounced reduction in MMDs during the 1-year treatment as compared to NON-MIDASRes (MIDASRes: T0: 23.5 ± 4.9 vs. T13: 7.7 ± 6.2; NON- MIDASRes: 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 RespondersT13 did not differ between MIDASRes (74.4%) and NON-MIDASRes (52.9%) patients (p = 0.058), while the percentage of RespondersT13 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 MIDASRes did not. Treatment discontinuation based on MIDASRes would have early excluded 36.0% of RespondersT13. Discontinuation based on "either MIDASRes or MMDRes" would have excluded a lower percentage (16%) of RespondersT13.

Conclusion: MIDASRes 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. MIDASRes: Patients with a MIDAS score reduction of at least 50% at T3. MMDRes: Patients with a MMDs reduction of at least 50% at T3. ResponderT13: 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.

Keywords: CGRP; Chronic migraine; Disability; Headache; Migraine; Monoclonal antibodies; Pain; Quality of life.

Conflict of interest statement

RDI: honoraria for scientific presentations from Eli-Lilly, and Teva. MA: honoraria for scientific presentations from Eli-Lilly. CT: personal fees for scientific presentations or participation in advisory boards from Allergan, Abbvie, Eli Lilly, Lundbeck, Novartis and Teva; PI or collaborator in clinical trials sponsored by Abbvie, Alder, Amgen, Eli-Lilly, IBSA, Lundbeck, Novartis and Teva; grants from the European Commission, the Italian Ministry of Health and the Italian Ministry of University and Research, Migraine Research Foundation, Abbvie; GS: honoraria for the participation in advisory boards or for oral presentations from: Eli-Lilly, Novartis and Teva. GV, NG, EG, DM, LA, MC, FB, FT, SB, FC: nothing to declare.

© 2022. The Author(s).

Figures

Fig. 1

Flowchart of enrolled patients. MIDAS: MIgraine Disability ASsessment. T6, T9, T12: follow-up visits at six, nine, and twelve months after first erenumab administration

Fig. 2

Timeline and study procedures. MIDAS: MIgraine Disability Assessment. MIDASRes: Patients with a MIDAS score reduction of at least 50% at T3. MMDRes: Patients with a MMDs reduction of at least 50% at T3. RespondersT13: Patients with a MMDs reduction from baseline of at least 50% in the last 4 weeks of observation period (after 13 erenumab administrations). T3, T6, T9, T12: follow-up visits at three, six, nine, and twelve months after first erenumab administration

Fig. 3

Changes in monthly migraine days, monthly headache days, and days of acute drugs intake in MIDASRes and MMDRes groups. MIDAS: MIgraine Disability Assessment. MIDASRes (green lines): Patients with a MIDAS score reduction of at least 50% at T3. NON-MIDASRes (red lines): Patients with a MIDAS score reduction < 50% at T3. MMDRes (orange lines): Patients with a MMDs reduction of at least 50% at T3. NON-MMDRes (blu lines): Patients with a MMDs reduction < 50% at T3. Black dotted lines represent changes in the overall study population. Δ: TIMExGROUP interaction < 0.050. Statistical analysis was performed with a non-parametric test for repeated measures, with the following factors: TIME: changes in the overall study population across the 1-year treatment period; GROUP: overall difference between study groups; TIMExGROUP interaction: different behavior of study groups across the 1-year treatment period. A: difference in monthly migraine days between MIDASRes and NON-MIDASRes groups. TIME = p < 0.001, GROUP = p = 0.034, TIMExGROUP = p = 0.045. B: difference in monthly migraine days between MMDRes and NON-MMDRes groups. TIME = p < 0.001, GROUP = p < 0.001, TIMExGROUP = p < 0.001.C: difference in monthly headache days between MIDASRes and NON-MIDASRes groups. TIME = p < 0.001, GROUP = p = 0.099, TIMExGROUP = p = 0.005. D: difference in monthly headache days between MMDRes and NON-MMDRes groups. TIME = p < 0.001, GROUP = p < 0.001, TIMExGROUP = p < 0.001. E: difference in days of acute drugs intake between MIDASRes and NON-MIDASRes groups. TIME = p < 0.001, GROUP = p = 0.424, TIMExGROUP = p = 0.045. F: difference in days of acute drugs intake between MMDRes and NON-MMDRes groups. TIME = p < 0.001, GROUP = p = 0.078, TIMExGROUP = p = 0.323

Fig. 4

Distribution of RespondersT13 according to MIDAS and MMDs reductions after 3 months of erenumab administration. MIDAS: MIgraine Disability Assessment. MMDs: monthly migraine days. RespondersT13: patients with a MMDs reduction from baseline of at least 50% in the last 4 weeks of observation period (after 13 erenumab administrations). The p-value in the box was calculated with a χ2 test. The tables in the top of the figure show the sensibility and specificity of being RespondersT13 according to reduction of at least 50% in MIDAS, MMDs, or "either MIDAS or MMDs". The green shadows in the tables highlight the parameters with the best accuracy in sensibility or specificity