CV followed up the patients and collected the blood samples. powered experiments. 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. 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 [2C5], whereas a more optimistic view foresees a remarkable safety profile, based on the concept that anti-CGRP and anti-CGRP 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 26, 2018 (https://www.ema.europa.eu/en/medicines/human/EPAR/aimovig), but only very recently the price negotiation (R)-P7C3-Ome process has been completed in Italy (https://www.gazzettaufficiale.it/eli/gu/2020/07/21/182/sg/pdf). During the time that erenumab was not commercially available, the drug has been provided through an expanded access program, and a limited number of patients have been treated at our Headache Clinics, em Fondazione Policlinico Gemelli IRCCS /em Academic Hospital in Rome. Having in mind the risk hypotheses postulated in our review [1], we used a previously validated CGRP radioimmunoassay (R)-P7C3-Ome [7] to measure the levels of circulating free CGRP in the plasma of patients included in the expanded access program of our Center, and treated with erenumab at approved dosages for at least 6?months. Seven patients with high-frequency episodic migraine, meeting the criteria of erenumab labeling, had a complete set of blood samples collected: all the patients received the 70-mg dose. Rabbit Polyclonal to Cytochrome P450 7B1 All patients provided an informed consent for use of biological samples, according to the rules of Gemelli Hospital, and the study protocol was approved by the Independent Ethics Committee of the hospital. We found (data expressed as pg CGRP/ml of plasma, the means SD of 7 replicates per group): 38.34??30.74 at baseline; 38.19??29.23 after 1?month of treatment (i.e. after a single administration); 53.89??28.03 after 6?months of treatment (i.e. at steady-state). Thus, the average increase in circulating CGRP after 6?months of erenumab treatment (R)-P7C3-Ome was about +?40% compared to both baseline and 1-month treatments, although such difference was not statistically significant because of huge SDs in all groups. We are fully aware of the limitations of this study. The number of patients included is small, and overall variability is subsequently high. Assuming a SD around 30?pg/ml, for a size effect of +?40% to be statistically significant, a sample size of at 55 subject is required, with a power of 80% and a risk of type-I error? ?5% in a two-tail test. Nonetheless, we believe it may be useful to publish this proof-of-concept study, in order to stimulate discussion on the issue of the biological effects of this new class of drugs, and possibly to prompt further, adequately powered studies on this topic. Such patho-physiological investigations might usefully complement the clinical studies that are currently under way to establish the effectiveness of erenumab in the real-world setting [8]. Acknowledgements Not applicable. Authors contributions GT.
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