Retrospective cohort study of anti-CGRP monoclonal antibody unresponsive migraine individuals treated with atogepant: The RESCUE study.

BackgroundA subset of individuals with episodic migraine (EM) and chronic migraine (CM) does not respond to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), even after switching agents. Although atogepant is effective in EM and CM, its role in individuals unresponsive to anti-CGRP mAbs remains to be elucidated. We hypothesize that atogepant may be a viable preventive option in these cases.MethodsWe conducted a retrospective cohort study in EM and CM individuals who discontinued anti-CGRP mAbs due to lack or loss of efficacy and were subsequently treated with atogepant. The primary endpoint was the ≥50% response rate in monthly headache days (MHDs). Secondary outcomes included ≥30% and ≥75% response rates in MHDs, response rates in monthly moderate-to-severe headache days (MSHDs), and changes in MHDs, MSHDs, acute medication days (AMDs) and Headache Impact Test (HIT-6). Patient Global Impression (PGI) scores and adverse events (AEs) were recorded.ResultsOf 213 screened records, 44 participants met inclusion criteria; 39 (88.6%) were female and 39 (88.6%) had CM. Prior use of anti-CGRP mAbs included erenumab in 11.4% of participants, galcanezumab in 52.3% and fremanezumab in 86.3%. After three months, 18.2% achieved a ≥50% reduction in MHDs; ≥30% and ≥75% response rates were 25.0% and 6.8% respectively. For MSHDs, ≥30%, ≥50% and ≥75% response rates were 47.6%, 33.3% and 19.0%, respectively. Median MHDs decreased from 24.5 (interquartile range (IQR) = 16.0-30.0; range 9.0-31.0) to 21.5 (IQR = 10.0-30.0; range 3.0-31.0; p = 0.011), and median MSHDs from 15.0 (IQR = 10.0-25.5; range 5.0-30.0) to 12.0 (IQR = 5.9-19.0; range 0.0-30.0; p = 0.001). AMDs and HIT-6 scores also showed significant reductions. According to the PGI scale, 59.1% of individuals reported some degree of improvement. AEs occurred in 50.0% of participants, most commonly constipation (31.8%). Five (11.4%) participants discontinued treatment due to side effects.ConclusionsAfter three months of treatment, atogepant led to a clinically meaningful improvement in a subset of participants. It may be a valuable preventive option for individuals unresponsive to anti-CGRP mAbs and warrants further investigation in prospective studies.