Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study

Abstract

Background Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data. Methods We analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients’ basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences. Results In total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine. Conclusions Patients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs.

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

“…The REFORM study's clinical deep phenotyping allows for exploration of clinical predictors for efficacy of erenumab, as well as treatment-induced biomarker changes and patterns in migraine and its subtypes. Previous studies have proposed several positive predictors of treatment response to mAbs against CGRP signaling, including unilateral pain localization [ 32 , 36 , 37 ], response to triptans [ 32 , 38 , 39 ], shorter duration of MOH [ 32 , 40 , 41 ], and older age [ 42 ]. In contrast, poor response has been associated with anxiety disorders and a higher number of failed preventive medications [ 34 , 40 , 43 ].…”

Effectiveness of three calcitonin gene-related peptide monoclonal antibodies for migraine: A 12-month, single-center, observational real-world study in Japan

“…Previous real-world studies evaluating two or more types of CGRP mAbs with three to six-month follow-up showed ≥50% response rates of 48.5–56.3% at three months (14,18–20) and 35.4–64.9% at six months (14,18,20). These response rates were comparable to those in the present study.…”

“…In a study of 260 patients with migraine receiving CGRP mAbs, typical migraine characteristics such as unilateral localization, pulsating character, photophobia or nausea were associated with ≥75% responders at three months, while CM, MOH, and concomitant depression were related to nonresponders (22). Older age, lower MMDs and fewer previous treatment failures were also associated with >50% responders at three months in a real-world study (19). Similar to previous studies, unilateral localization, pulsatile nature (18,22), less comorbid MOH (22), fewer prophylactics used previously, and fewer baseline MMDs (19) were related to responders in our study.…”

“…Older age, lower MMDs and fewer previous treatment failures were also associated with >50% responders at three months in a real-world study (19). Similar to previous studies, unilateral localization, pulsatile nature (18,22), less comorbid MOH (22), fewer prophylactics used previously, and fewer baseline MMDs (19) were related to responders in our study. Regarding the effect of aura on clinical efficacy, in logistic regression analysis, the presence of aura did not remain a predictor of responders, but it was associated with ≥50% responders at six and 12 months.…”

“…The results showed similar efficacy (MMD reduction from baseline by 14 to 17 days) for all three CGRP mAbs, but a description of the statistics regarding between-group comparisons was not found. Unlike our study, several previous real-world studies examining the efficacy of CGRP mAbs have excluded patients with a history of CGRP mAb use (18,19,37). Because the efficacy of the three CGRP mAbs may be affected in patients with a history of CGRP mAb use when refractory patients are included, we also performed a subanalysis of the effect of the three CGRP mAbs only in CGRP mAb-naı¨ve patients.…”