A proof-of-concept study on CGRP plasma levels of migraineurs during a 6-month treatment with ERENUMAB
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(2020) 21:124
The Journal of Headache and Pain
SHORT REPORT
Open Access
A proof-of-concept study on CGRP plasma levels of migraineurs during a 6-month treatment with ERENUMAB Giuseppe Tringali1, Catello Vollono2,3, Paolo Calabresi3,4 and Pierluigi Navarra1,5* Abstract The introduction of monoclonal antibodies (mAbs) against calcitonin-gene related peptide (CGRP) or CGRP receptors in the treatment of migraine raised concerns on the possible risks associated to the long-term inhibition of CGRP physiological functions. In this proof-of-concept study, we have measured the circulating levels of CGRP in 7 patients with high-frequency episodic migraine receiving the anti-CGRP receptor mAb erenumab for at least 6 months, to test the hypothesis that long-term blockade of CGRP receptors induces an increase in systemic CGRP levels via a classical up-regulation mechanism. Plasma CGRP levels were measured by a validated radioimmunoassay at baseline, and after 1 and 6 months of treatment with erenumab, 70 mg given sc every 4 weeks. We found (data expressed as the means ± SD): 38.34 ± 30.74 pg CGRP/ml of plasma at baseline, 38.19 ± 29.23 pg/ml after 1 month and 53.89 ± 28.03 pg/ml after 6 months of treatment. Thus, the average increase in plasma CGRP levels after 6 months of treatment was about + 40% compared to both baseline and 1-month treatments; such difference was not statistically significant because of high SD values in all groups. These preliminary findings need to be confirmed in larger, sufficiently powered experiments. Keywords: CGRP, CGRP receptor, Monoclonal antibodies, Erenumab, Migraine In the June 2019 issue, the journal Peptides published our last work on calcitonin gene-related peptide (CGRP), a review dealing with the anti-CGRP and anti-CGRP receptor monoclonal antibodies (mAbs) recently introduced for migraine treatment [1]. The paper addressed the concerns raised by the potential risks ensuing a long-term inhibition of CGRP functions, and we discussed whether the different action mechanisms of these mAbs (i.e. quenching systemic CGRP vs blocking its receptors) might be associated to different safety profiles. * Correspondence: [email protected] 1 Department of Healthcare Surveillance and Bioethics, Section of Pharmacology, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy 5 Pharmacology - Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy Full list of author information is available at the end of the article
Among other issues, we made a point of measuring plasma CGRP levels during long-term treatments with anti-CGRP mABs [1]. Concerns about the potential risks associated to long-term blockade of CGRP or CGRP receptor are shared by several groups [2–5], whereas a more optimistic view foresees a remarkable safety profile, based on the concept that anti-CGRP and antiCGRP receptor mAbs knockdown, but do not knockout CGRP signaling [6]. First-in-class mAb, the anti-CGRP receptor erenumab obtained a marketing authorization in the European Union on July 2
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