Switching Anti-CGRP Monoclonal Antibody Therapy in Nonresponders with Migraine May Reduce Monthly Headache Days
Subgroup analyses found no significant difference in efficacy based on change in therapeutic action (ie, CGRP vs its receptor), doses, or intertreatment interval.
Switching between anti-CGRP monoclonal antibodies (mAbs) significantly reduced monthly headache days (MHDs) in patients with migraine who did not respond to initial treatment, according to a new retrospective study published in the journal Headache. Among 185 study participants, the median MHDs decreased significantly from 27.0 at baseline to 21.0 at 3 months and to 20.0 at 6 months (both P <.001).
Response was observed regardless of whether the therapeutic action was changed (ie, CGRP vs its receptor), with approximately 18% achieving a 50% or greater reduction in MHDs at 3 months, according to Alex Jaimes, MD, and colleagues at Fundación Jiménez Díaz University Hospital in Madrid.
Jaimes et al conducted the retrospective cohort study at a tertiary headache center evaluating records of adults treated with anti-CGRP mAbs between January 202 and March 2024.
The team reported that although the median change in MHDs from baseline to 3 months was 0.0 days (IQR –5.5 to 0.0), 1 in 4 participants achieved a reduction of at least 5 days, and some improved by as many as 30 days. Similarly, at 6 months, the median change in MHDs was –0.7 days (IQR –5.7 to 0.0), with 15.4% achieving a a response of 50% or higher and 25% improving by at least 5 days. They added, however, that some participants did not improve during either period.
Findings from a subgroup analysis conducted to evaluate potential differences in outcomes based on mechanism of mAb action showed no significant difference based on whether participants switched to a mAb targeting the same mechanism (43.2%) or a different one (56.8%). At 3 months, median MHDs were 23.0 in the same-target group versus 19.0 in the changed-target group (P = .144). At 6 months, they were 24.0 and 17.0, respectively (P = .170). Response rates (50% or greater reduction in MHD) were also similar between groups at both time points, with no statistically significant differences.
The investigators also found that the number of doses received before switching medications and the interval between treatments did not significantly affect outcomes. The likelihood of achieving a 50% or greater response was unrelated to either variable (odds ratio 1.0 for both).
mAbs targeting CGRP or its receptor have accumulated a wide and robust evidence base in both clinical trials and real-world settings for their efficacy and safety, Alex Jaimes, MD, and colleagues at Fundación Jiménez Díaz University Hospital in Madrid, wrote. However, despite an average of 50% of individuals with migraine achieving a 50% or greater reduction in both monthly headache and migraine days, Diaz et al cite research that shows “a noteworthy proportion of patients discontinue treatment due to either ineffectiveness or adverse effects.2”
Despite an average of 50% of individuals with migraine achieving a 50% or greater reduction in both monthly headache and migraine days, Diaz et al cite research that shows “a noteworthy proportion of patients discontinue treatment due to either ineffectiveness or adverse effects.2”
The researchers also pointed to several series and studies that found when switching is the result of lack of effect or side effects, “approximately 29% to 45.4% of patients achieve a [response rate of 30% or greater], and 12% to 42.8% experience a [50% or greater] response.3,4 But the data on mAb switching remains sparse, they observed, and is “essential for clinical practice and guidelines.” These observations provided impetus for the current study.
The study cohort was predominantly women (81.6%), with a mean age of 48.6 years. Most participants (92.4%) had chronic migraine, and 27.1% reported migraine with aura. The median age at migraine onset was 14 years, and the median migraine duration was 32 years. Patients had tried a median of 8 prior preventive therapies and 51.9% were receiving concurrent oral migraine preventives at the time of switching. The researchers noted that 63.8% had a psychiatric comorbidity.
Jaimes and colleagues acknowledge several limitations to the study, including its retrospective design, approaches used to account for missing data, and the absence of a control group. Not all patients consistently recorded headache or medication use data, and those with medication-overuse headache were not analyzed separately.
Despite these limitations, they concluded that the findings support switching anti-CGRP mAbs as a viable strategy for patients who do not respond to initial migraine therapy. The also called for further research to fully explore the clinical implications of their findings, particularly given the study’s modest sample size, which limited its power to detect small differences.
