Cerebral Blood Flow and Other Predictors of Responsiveness to Erenumab and Fremanezumab in Migraine—A Real-Life Study

Nowaczewska, Magdalena; Straburzyński, Marcin; Waliszewska‐Prosół, Marta; Meder, Grzegorz; Janiak-Kiszka, Joanna; Kaźmierczak, Wojciech

doi:10.3389/fneur.2022.895476

Cited by 24 publications

(26 citation statements)

References 33 publications

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“…Our results suggest that ≥ 50% CGRPmAb response is significantly associated with older age, fewer MHD, and fewer prior treatment failures, and can be predicted based on age, total prior treatment failures, and immunorheumatologic medical history. Several parameters that are reportedly associated with response, such as medication overuse [11,17,19], unilateral pain localisation [15], medical history of psychiatric disease [14,20], and MMD [18], were not significantly different between responders and non-responders in the present study.…”

Section: Discussioncontrasting

confidence: 66%

“…The literature to date has shown that the response to CGRPmAbs is positively associated with a lower number of failed preventative medications [11][12][13][14], unilateral pain localisation [13][14][15], better response to triptans [13,16], lower number of monthly analgesic intakes at baseline [11,17,18], shorter duration of medication-overuse headache (MOH) [11,13,17,19], and lower body mass index (BMI) [13], and negatively associated with the existence of psychiatric conditions [14,20]. However, the results of these real-world studies have not always been consistent.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Discussioncontrasting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…Despite several attempts, clear predictors of response could not be determined in the registration trials. In a few real-world studies, unilateral pain localization, and triptan responsiveness were positively associated with a better treatment response [ 17 – 21 ]. On the contrary, psychiatric comorbidities, a long disease duration and a high number of previously failed preventive treatments were associated with a lower response [ 17 , 18 , 22 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical evaluation of super-responders vs. non-responders to CGRP(-receptor) monoclonal antibodies: a real-world experience

et al. 2023

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Background Clinical trials and real-world studies revealed a spectrum of response to CGRP(-receptor) monoclonal antibodies (mAbs) in migraine prophylaxis, ranging from no effect at all to total migraine freedom. In this study, we aimed to compare clinical characteristics between super-responders (SR) and non-responders (NR) to CGRP(-receptor) mAbs. Methods We performed a retrospective cohort study at the Headache Center, Charité – Universitätsmedizin Berlin. The definition of super-response was a ≥ 75% reduction in monthly headache days (MHD) in the third month after treatment initiation compared to the month prior to treatment begin (baseline). Non-response was defined as ≤ 25% reduction in MHD after three months of treatment with a CGRP-receptor mAb and subsequent three months of treatment with CGRP mAb, or vice versa. We collected demographic data, migraine disease characteristics, migraine symptoms during the attacks in both study groups (SR/NR) as well as the general medical history. SR and NR were compared using Chi-square test for categorical variables, and t-test for continuous variables. Results Between November 2018 and June 2022, n = 260 patients with migraine received preventive treatment with CGRP(-receptor) mAbs and provided complete headache documentation for the baseline phase and the third treatment month. Among those, we identified n = 29 SR (11%) and n = 26 NR (10%). SR reported more often especially vomiting (SR n = 12/25, 48% vs. NR n = 4/22, 18%; p = 0.031) and typical migraine characteristics such as unilateral localization, pulsating character, photophobia and nausea. A subjective good response to triptans was significantly higher in SR (n = 26/29, 90%) than in NR (n = 15/25, 60%, p = 0.010). NR suffered more frequently from chronic migraine (NR n = 24/26, 92% vs. SR n = 15/29, 52%; p = 0.001), medication overuse headache (NR n = 14/24, 58% versus SR n = 8/29, 28%; p = 0.024), and concomitant depression (NR n = 17/26, 65% vs. SR n = 8/29, 28%; p = 0.005). Conclusion Several clinical parameters differ between SR and NR to prophylactic CGRP(-R) mAbs. A thorough clinical evaluation prior to treatment initiation might help to achieve a more personalized management in patients with migraine.

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“…Atogepant displays the largest potency difference (35-210 times more potent in human middle meningeal artery), which seems favorable in view of the cardiovascular profile. However, efficacy, as well as safety, also depend on many other factors, such as plasma-protein binding, dosing, dosing intervals, duration of receptor antagonism in vivo and metabolism of the drug, as well as patient characteristics, such as the potential predominance of CGRP in the pathophysiology of their migraine attacks [30,31] and/or genetic polymorphisms in the CGRP receptor gene components [32]. Telcagepant, ubrogepant and zavegepant show a Schild plot slope in h coronary arteries that does not differ from unity, whereas for atogepant, olcegepant and gepant, the Schild slope is significantly less than unity.…”

Section: Discussionmentioning

confidence: 99%

Blocking the CGRP Receptor: Differences across Human Vascular Beds

Vries

Boucherie

Bogaerdt³

et al. 2023

Pharmaceuticals

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Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for the treatment of migraine. Here, the effect of the small-molecule CGRP receptor antagonist zavegepant (0.1 nM–1 µM) on CGRP-induced relaxation in isolated human coronary arteries (HCAs) was investigated. A Schild plot was constructed and a pA2 value was calculated to determine the potency of zavegepant. The potency and Schild plot slopes of atogepant, olcegepant, rimegepant, telcagepant, ubrogepant and zavegepant in HCAs and human middle meningeal arteries (HMMAs), obtained from our earlier studies, were compared. Zavegepant shifted the concentration–response curve to CGRP in HCAs. The corresponding Schild plot slope was not different from unity, resulting in a pA2 value of 9.92 ± 0.24. No potency difference between HCAs and HMMAs was observed. Interestingly, olcegepant, atogepant and rimegepant, with a Schild plot slope < 1 in HCAs, were all >1 log unit more potent in HMMAs than in HCAs, while telcagepant, ubrogepant and zavegepant, with a Schild plot slope not different from unity, showed similar (<1 log difference) potency across both tissues. As a Schild plot slope < 1 may point to the involvement of multiple receptors, it is important to further identify the receptors involved in the relaxation to CGRP in HCAs, which may be used to improve the cardiovascular safety of future antimigraine drugs.

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Cerebral Blood Flow and Other Predictors of Responsiveness to Erenumab and Fremanezumab in Migraine—A Real-Life Study

Cited by 24 publications

References 33 publications

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

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

Clinical evaluation of super-responders vs. non-responders to CGRP(-receptor) monoclonal antibodies: a real-world experience

Blocking the CGRP Receptor: Differences across Human Vascular Beds

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