Effectiveness of switching strategies in CGRP monoclonal antibody therapy for migraine: A retrospective cohort study

Abstract

Objective: To evaluate the effectiveness of first switching between monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor in the treatment of migraine.

Background: Although mAbs targeting CGRP or its receptor have emerged as a leading treatment for migraine prevention, a proportion of patients do not respond. While switching between these antibodies is a common clinical practice in such cases, the effectiveness remains a subject of study.

Methods: We conducted a retrospective cohort study at a tertiary headache center, analyzing data from clinical records of patients treated with anti-CGRP mAbs from January 2020 to March 2024. Baseline was defined as the monthly headache days (MHDs) in the 3 months prior to the start of the second mAb. The primary endpoint was the change in MHDs at month 3 and month 6 following the switch. Additionally, we evaluated response rates in both periods. Subgroup analyses were conducted based on changes in mechanism of action. Finally, we assessed the influence of the number of doses of the first mAb and the inter-treatment interval.

Results: Out of 1244 initially identified patients, 185 were included in the month-3 analysis and 123 in the month-6 evaluation. The median MHDs decreased from 27.0 (interquartile range [IQR] 16.1, 30.0; range 5.0, 30.7) at baseline to 21.0 (IQR 10.0, 30.0; range 0.0, 30.0; p < 0.001) at month 3, and to 20.0 (IQR 10.0, 30.0; range 0.0, 31.0; p < 0.001) at month 6. Subgroup analyses revealed no significant differences in MHDs between maintaining the same target or changing it (baseline: 28.0 [IQR 16.2, 30.0; range 5.0, 31.0] vs. 27.0 [IQR 6.0, 31.0; range 6.0, 31.0]; month 3: 23.0 [IQR 10.0, 30.0; range 0.0, 31.0] vs. 19.0 [IQR 11.0, 30.0; range 1.0, 31.0], p = 0.144; month 6: 24.0 [IQR 11.0, 30.0; range 0.0, 31.0] vs. 17.0 [IQR 10.0, 30.0; range 3.0, 31.0], p = 0.170). There was no association between a ≥50% reduction in MHDs and the number of previous doses of the first mAb (odds ratio [OR] 1.0; 95% confidence interval [CI] 1.0, 1.1; p = 0.189) or the inter-treatment interval (OR 1.0; 95% CI 0.9, 1.1; p = 0.914).

Conclusion: Switching between anti-CGRP mAbs resulted in a reduction in MHDs, with no significant differences based on the mechanism of action. Factors such as the number of doses of the first mAb and the inter-treatment interval did not appear to predict a ≥50% reduction in MHDs at month 3. Our findings support the viability of switching as an effective treatment option for patients with migraine who do not respond to initial mAb therapy.

Keywords: calcitonin gene–related peptide; headache; migraine; monoclonal antibody; switch.

FIGURE 1

Flowchart of patient selection. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Distribution of median number of first mAb doses. CGRP, calcitonin gene–related peptide; mAb, monoclonal antibody. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Bar chart illustrating the reasons for switching. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Histogram depicting the median gap in months between the first and second anti‐calcitonin gene–related peptide monoclonal antibody. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

Box plot illustrating the median monthly headache days at baseline and over the following 6 months. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 6

Sankey diagram illustrating the type of switch and the percentage of patients with a ≥50% reduction in monthly headache days at month 3. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 7

Bar chart illustrating the cumulative response rates at month 3 and month 6. [Colour figure can be viewed at wileyonlinelibrary.com]