Of the 5655 patients with the diagnosis of migraine in the NTD migraine registry, 670 patients (11.8%) received at least one anti-CGRP(-R) mAb for migraine prophylaxis. Of those, 655 patients met our inclusion criteria and were included in the study. The 15 excluded patients had either less than 4 MMDs at baseline or were less than 18 years old. The included patients were followed up for an average of 730 ± 470 days.

Baseline characteristics of the whole cohort, and by total number of switches during the observation period are displayed in Table 1. Of the 655 patients, 479 (73.1%) did not switch their antibody during the observation period, while 135 patients switched once (20.6%), 35 patients switched twice (5.4%), and 6 patients switched 3 or more times (0.9%). The average duration of a completed treatment cycle was 532 ± 438 days. For the no switch, one switch and two-switches subgroups, the average durations of the first completed treatment cycle were 679 ± 479, 338 ± 247, and 292 ± 243 days respectively. Data from the group of patients with 3 or more switches are not shown due to the low number of patients in this group.

Patients who switched were more likely to have comorbid depression (OR: 1.74, 95% CI: 1.19–2.52), comorbid anxiety disorder (OR: 2.22, 95% CI: 1.13–4.30), medication overuse at baseline (OR: 1.60, 95% CI: 1.08–2.34), chronic migraine (OR 3.54, 95% CI: 2.36–5.32), and to have had previous prophylactic therapy with onabotulinumtoxinA (OR 2.21, 95% CI: 1.49–3.27), which in Germany is required for treatment with anti-CGRP mAbs in chronic migraine.

The highest number of patients (n = 427) initially received erenumab, which was the first available mAb in Germany. Of these, 134 (31.4%) went on to switch either to fremanezumab or galcanezumab. Twenty-two (14.2%) of the 150 patients who started with fremanezumab switched either to erenumab or galcanezumab, and 16 (20.5%) out of 78 patients who started with galcanezumab switched to either erenumab or fremanezumab. Most recorded switches (192 out of 221 switches, 86.9%) were either from an anti-CGRP-receptor to ligand mAb, or from an anti-CGRP-ligand to receptor mAb. Of the 172 first switches, only 9 (5.23%) were within the anti-CGRP ligand group. The number of patients receiving erenumab, fremanezumab or galcanezumab in their first up to sixth treatment attempt with an anti-CGRP(-R) mAb is displayed in Table 2.

Of the 6 patients who switched 3 times or more, 5 patients switched 3 times, and one patient switched 5 times. The maximum number of switches recorded was 5 times. A Sankey diagram of the switching pattern is shown in Fig. 1. The proportion of treatment cycles that were aborted before month 6 were 11.1% (53 out of 479 treatment cycles), 8.23% (22 out of 267 treatment cycles), and 13.3% (14 out of 105 treatment cycles) for the no switch, one switch, and two switches subgroups respectively.

Sankey diagram of switching patterns among erenumab, fremanezumab and galcanezumab

In patients who did not switch, a ≥ 50% reduction in MMD was achieved by 51.0% of patients at 3 months, and 64.7% of patients at 6 months (Fig. 2B). The mean MMD decreased from 9.90 (SD 4.50) days at baseline to 4.53 (SD 3.86) days by 6 months (change in mean MMD: -5.37, Fig. 2A).

Results for the no switch subgroup. Mean monthly migraine days (MMD) during the first 6 months of treatment (A), percentage of patients achieving ≥ 50% reduction in MMD at 3 and 6 months (B), average HIT-6 (C) and MIDAS (D) scores at baseline, 3 and 6 months for the no switch subgroup. Error bars represent 95% confidence intervals

MIDAS total scores improved from 62.7 (SD 48.9) at baseline to 34.5 (SD 42.4) at month 6 and HIT-6 scores improved from 65.3 (SD 4.09) to 57.9 (SD 8.60, Fig. 2C-D). Remaining results including MHD, ≥ 50% response rates for MHD, and MDAM during the first 6 months of therapy for all subgroups are displayed in Figures S1-S3.

In the one switch subgroup, 33.0% and 41.2% of patients reached a ≥ 50% reduction in MMD at 3 and 6 months during the treatment cycle with the first anti-CGRP(-R) mAb. During the second treatment cycle after switching to a different anti-CGRP(-R) mAb, the ≥ 50% response rates for MMD were slightly higher with 42.7% at 3 months and 50.7% at 6 months (Fig. 3B). Mean MMD decreased from 12.3 (SD 5.85) at baseline to 7.44 (SD 5.33, change in mean MMD: -4.86) at 6 months in the first treatment cycle, and from 12.2 (SD 5.79) at baseline to 6.33 (SD 5.21, change in mean MMD: -5.87) at 6 months during the second treatment cycle (Fig. 3A).

Results for the one switch subgroup. Mean monthly migraine days (MMD) during the first 6 months (A), percentage of patients achieving ≥ 50% reduction in MMD at 3 and 6 months (B), average HIT-6 (C) and MIDAS (D) scores at baseline, 3 and 6 months during the first and second treatment cycles of the one switch subgroup. Error bars represent standard errors of the mean

From baseline to month 6 of therapy, MIDAS scores improved from 67.1 (SD 44.8) to 45.1 (SD 48.9) during the first treatment cycle, and from 68.2 (SD 48.9) to 42.0 (SD 47.3) during the second treatment cycle (Fig. 3D). HIT-6 scores changed from 64.9 (SD 5.10) to 61.1 (SD 6.04), and from 65.6 (SD 4.60) to 60.4 (SD 6.28) during the first 6 months of the first and second treatment cycles respectively (Fig. 3C).

In the group of patients who switched twice, the ≥ 50% response rates for MMD at month 3 were 34.5%, 25.0%, and 31.6% for the first, second and third treatment cycles respectively. At 6 months, the proportion of patients achieving a ≥ 50% reduction in MMD were 52.9%, 20.0% and 25.0% for the first, second and third treatment cycles respectively (Fig. 4B). Mean MMD decreased from 14.7 (SD 6.88) and 14.4 (SD 6.55) at baseline to 8.79 (SD 7.09, change in MMD − 5.91) and 9.61 (SD 3.71, change in mean MMD − 4.79) at 6 months during the first and second treatment cycles respectively. In the third treatment cycle, the decrease in mean MMD was lower, from 14.4 (SD 6.55) at baseline to 12.5 (SD 7.30, change in mean MMD − 1.84) at 6 months (Fig. 4A).

Results for the two switches subgroup. Mean monthly migraine days (MMD) during the first 6 months (A), percentage of patients achieving ≥ 50% reduction in MMD at 3 and 6 months (B), average HIT-6 (C) and MIDAS (D) scores at baseline, 3 and 6 months during the first, second, and third treatment cycles of the two switches subgroup. Error bars represent standard errors of the mean

MIDAS and HIT-6 scores did not improve for the two switches subgroup during their treatment cycles (Fig. 4C-D). Mean MIDAS total scores at 6 months were even higher with increasing number of switches, with 33.6 (SD 30.6), 57.3 (SD 50.8), and 66.4 (SD 56.8) for the first, second and third treatment cycles respectively (Fig. 4D).