A total of 62 patients (31 in the galcanezumab group and 31 in the OMPM group) were included in the study. The baseline characteristics are displayed in Table 1. The median age among all participants was 36.6 years (IQR: 29.0–48.0), and 51 (82%) were female. Mean monthly migraine days were 12.5. Myofascial pain syndrome was the most common comorbidity (24%), followed by depression (23%) and anxiety (9%). The overall median MIDAS score was 27.5 (IQR: 13–60). The most common acute medication used were NSAID (46.8%), acetaminophen (25.8%) and triptan (22.6%), respectively. The most commonly used preventive medications were tricyclic antidepressants (29%), beta-blockers (18%), and antiseizure medications (15%), respectively. In terms of headache classification, 47% of patients had HFEM, while 53% had CM. There were no statistically significant differences in baseline characteristics between the two groups.

Responder rate in achieving VLFEM

The cumulative incidence of participants achieving VLFEM increased over time in both the OMPM and galcanezumab groups (Fig. 1). Kaplan-Meier analysis showed that patients initiating galcanezumab had significantly higher conversion rates to VLFEM compared to OMPM: 29.0% vs. 6.5% at month 1, 45.2% vs. 19.4% at month 3, and 52.9% vs. 32.4% at month 6 (p = 0.03). In a subgroup analysis by baseline migraine class, patients with HFEM receiving galcanezumab had significantly higher rates of achieving VLFEM compared to OMPM: 50.0% vs. 6.7% at month 1, 78.6% vs. 33.3% vs. month 3, and 85.7% vs. 40.0% at month 6 (p < 0.001) (Fig. 2A). There were no significant differences among patients with CM at baseline (Fig. 2B). A multivariable Cox proportional hazards model showed galcanezumab use was significantly associated with higher rates of achieving VLFEM (adjusted odds ratio [aOR] 3.55; 95%CI 1.56–8.04, p = 0.002).

Table 1 Baseline characteristics of all 62 participantsFig. 1

Kaplan-Meier plots showing the cumulative incidence of patients achieving VLFEM among galcanezumab group (orange line), OMPM group (blue line), and overall (green line) over 6 months follow-up period

Abbreviation: OMPM: oral migraine preventive medication; VLFEM: very low-frequency episodic migraine

Fig. 2

Kaplan-Meier plots showing the cumulative incidence of participants achieving VLFEM among galcanezumab group (orange line), OMPM group (blue line), and overall (green line) over 6 months follow-up period categorized by baseline migraine class: (A) HFEM; (B) CM

Abbreviation: CM: chronic migraine; HFEM: high-frequency episodic migraine; OMPM: oral migraine preventive medication; VLFEM: very low frequency episodic migraine

Improvements in migraine classes categorized by baseline diagnosis

Patients with CM in both the galcanezumab and OMPM groups had similar proportion achieving VLFEM at month 3 (11.8% [2/17] vs. 12.5% [2/16]). However, the difference was more pronounced among those with HFEM (64.3% [9/14] vs.13.3% [2/15]) (Fig. 3). A similar trend was observed at 6 months, with 23.5% [4/17] of galcanezumab group with CM and 25% [4/16] of OMPM group with CM at baseline achieving VLFEM, and 64.3% [9/14] of the galcanezumab group with HFEM and 20.0% [3/15] of OMPM group with HFEM at baseline achieving VLFEM.

Importantly, the galcanezumab group showed a higher proportion of patients with improvement in their migraine classes from baseline compared to OMPM group at both 3 and 6 months. At month 3, 64.5% [20/31] of patients receiving galcanezumab had improvements, including 85.7% [12/14] of those with HFEM and 47.1% [8/17] of those with CM, compared to 51.6% [16/31] of patients receiving OMPM, with 60.0% [9/15] of those with HFEM and 43.8% [7/16] of those with CM. At month 6, 77.4% [24/31] of the galcanezumab group had improvements in their migraine class, with 92.9% [13/14] of HFEM and 64.7% [11/17] of CM, compared to 58.1% [18/31] in the OMPM group, with 46.7% [7/15] of HFEM and 68.8% [11/16] of CM (Table 2).

Fig. 3

Sankey diagrams illustrating changes in migraine class from baseline to months 3 and 6: (A) Galcanezumab group; (B) OMPM group

Abbreviation: CM: chronic migraine; HFEM: high-frequency episodic migraine; LFEM: low-frequency episodic migraine; OMPM: oral migraine preventive medication; VLFEM: very low-frequency episodic migraine

Table 2 Proportion of participants with any improvements in migraine class from the baseline diagnosis at months 3 and 6Changes in migraine classes categorized by baseline diagnosis

For patients with HFEM at baseline, a higher proportion of the galcanezumab group transitioned to VLFEM at month 3 (64.3% vs. 13.3% in the OMPM group). Fewer patients in the galcanezumab group shifted to LFEM (21.4% vs. 46.7%) or remained in HFEM (14.3% vs. 20%). By month 6, this trend continued, with more patients in the galcanezumab group achieving VLFEM (64.3% vs. 20% in the OMPM group). Transitions to LFEM were more balanced (28.6% for galcanezumab vs. 26.7% for OMPM), while fewer patients receiving galcanezumab remained in HFEM (7.1% vs. 26.7%). Notably, none of the patients with HFEM at baseline who received galcanezumab progressed to CM (0% vs. 20.0% at month 3; 0% vs. 26.7% at month 6) (Fig. 4A and B).

For patients with CM at baseline, both groups showed similar patterns of transitioning to different migraine classes at month 3: 11.8% of the galcanezumab group and. 12.5% of the OMPM group transitioned to VLFEM; 23.5% and 18.8% transitioned to LFEM; 11.8% and 12.5% transitioned to HFEM; while 52.9% and 56.2% remained in CM, respectively. By month 6, a higher proportion of patients with CM at baseline in both groups transitioned to VLFEM (23.5% for galcanezumab vs. 25% for OMPM). However, fewer patients in the galcanezumab group shifted to LFEM (5.9% vs. 31.2% for OMPM), while more shifted to HFEM (35.3% vs. 12.5% for OMPM). Both groups showed a similar percentage of those remaining in CM (35.3% vs. 31.2% for OMPM) (Fig. 5A and B).

Fig. 4

Migraine class among those with HFEM at baseline at month 3 (A) and month 6 (B) after follow-up

Abbreviations: CM: chronic migraine; HFEM: high-frequency episodic migraine; LFEM: low-frequency episodic migraine; OMPM: oral migraine preventive medication; VLFEM: very low-frequency episodic migraine

Fig. 5

Migraine class among those with CM at baseline at month 3 (A) and month 6 (B) after follow-up

Abbreviations: CM: chronic migraine; HFEM: high-frequency episodic migraine; LFEM: low-frequency episodic migraine; OMPM: oral migraine preventive medication; VLFEM: very low-frequency episodic migraine

The trend in reduction of headache days between OMPM and galcanezumab group

Figure 6 shows a comparison of the trend in the reduction of migraine headache days between the OMPM and galcanezumab groups. The key finding is the slope of the graph. In the galcanezumab group, a linear decrease in the number of headache days was observed, with a sustained reduction in migraine headache days. In contrast, the OMPM group exhibited a more fluctuating response without sustained improvement.

Fig. 6

Mean changes in monthly headache days with 95%CI categorized by the two groups: (A) Galcanezumab; (B) OMPM

Abbreviation: MHDs: monthly headachy days; OMPM: oral migraine preventive medication

Sustaining VLFEM between OMPM and galcanezumab group

A total of 15 patients achieved VLFEM at month 3: 11 from the galcanezumab group and 4 from the OMPM group. Among the galcanezumab group, 9 patients (81.8%) were able to sustain VLFEM through month 6. In contrast, only 2 patients (50.0%) in the OMPM group maintained VLFEM from month 3 to month 6.

Comparison in achieving VLFEM between HFEM and CM in the Galcanezumab group

In the galcanezumab group, patients with HFEM were more likely to achieve VLFEM than those with CM at both month 3 and month 6 (78.6% vs. 17.8% and 85.7% vs. 25.9%, respectively, p < 0.001). These findings strongly support the notion that early initiation of galcanezumab could lead to better outcomes (Fig. 7).

Fig. 7

Kaplan-Meier plots showing the cumulative incidence of participants achieving VLFEM among galcanezumab group, categorized by baseline migraine class: HFEM (blue line), CM (orange line), and overall (green line) over 6 months follow-up period

Abbreviation: CM: chronic migraine; HFEM: high-frequency episodic migraine; VLFEM: very low-frequency episodic migraine