Monoclonal Antibodies Against CGRP (R): Non-responders and Switchers: Real World Data from a Large Case Series

Abstract

ObjectiveAssessement of the responder and non-responder rate to consecutive monoclonal CGRP-antibody (CGRP-mAb) treatment, the presence of side effects, analysis of predictors of response and loss of efficacy evaluation over time. Methods We conducted a retrospective analysis including 171 patients with episodic (EM) or chronic migraine (CM), who received one, two or three different CGRP-(R)-mAbs. Non-response was defined as ≤50% reduction of monthly migraine days (MMDs) in EM and ≤ 30% reduction of MMDs in CM after 3 months of treatment. Results71.9% responded to the first mAb. Side effects led to treatment discontinuation in 5.3%. Of the 26 patients who did not respond to the first mAb or experienced a loss of efficacy over time, 11 (42.3%) responded to the second and two of 7 to the third monoclonal antibody. Poor response to therapy was associated with a higher monthly headache frequency (p = 0.042), pre-existing psychiatric disorder (p = 0.032), and a higher number of prior preventive migraine therapies (p = 0.022).ConclusionOur findings support mAb-class switch in non-responders or in patients experiencing a loss of efficacy. The use of a third CGRP-mAb could be beneficial for some patients. Early use of CGRP-mAbs in the prevention of migraine might help to avert chronification of migraine and treatment-refractory patients.

Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies – insights from the German NeuroTransData registry

“…This is comparable to ≥ 50% response rates seen in patients on their second anti-CGRP(-R) mAb in some other studies, e.g. 42.8% (59/138) in a real world study with fremanezumab (Finesse) at three months [19], and 42.3% (11/26) in an Austrian case series [9]. Other studies with limited sample sizes reported lower ≥ 50% response rates after switching: 13.6% (3/22) In the group of patients with two switches, the ≥ 50% response rate and mean reduction in MHD and MMD at six months were distinctly lower, in particular during the third treatment cycle, while the baseline MHD and MMD were higher than in the other subgroups.…”

“…In real-world observational studies, the ≥ 50% response rates to anti-CGRP(-R) mAbs range from 50% to 70% depending on baseline patient characteristics and duration of therapy, leaving 30%-50% of patients not benefiting significantly from treatment. Accumulating recent reports of non-responders to anti-CGRP(-R) mAbs and switchers [6,8,9,18,19], highlight the fact that, while anti-CGRP(-R) mAbs are highly effective and well-tolerated medications, they are not the panacea patients sometimes hope for, and have relevant limitations. This could be due to alternative neuropeptides and signaling pathways involved in migraine pathogenesis playing a more crucial role in the non-responders [20,21].…”

“…A treatment attempt with a second anti-CGRP(-R) mAb can eventually result in a clinically significant improvement in up to 45% of patients [6][7][8]. If no response was seen after the first switch, a second switch may still lead to a positive treatment outcome [9].…”