a Mass Spectrometry Laboratory Unit, Sant'Andrea University Hospital , Rome , Italy.
b Department of Human Neurosciences, Sapienza University of Rome , Rome , Italy.
Expert Rev Clin Pharmacol. 2019 Aug;12(8):741-748. doi: 10.1080/17512433.2019.1635452. Epub 2019 Jun 26.
: The Calcitonin Gene-Related Peptide (CGRP) has been implicated in migraine pathophysiology due to its role in neurogenic inflammation and transmission of trigeminovascular nociceptive signal. New molecules targeting CGRP and its receptor have been developed as migraine-specific preventative treatments. Fremanezumab (or TEV-48,125, LBR-101), a human monoclonal antibody against CGRP, has been recently approved for clinical use by FDA and EMA. : This paper briefly discusses the calcitonin family of neurotransmitters and resultant activation pathways and in-depth the chemical properties, pharmacodynamics, pharmacokinetics, clinical efficacy and safety of Fremanezumab for the prophylactic treatment of migraine. : Fremanezumab, a migraine-specific drug, is effective and safe as a prophylactic treatment of chronic and episodic migraine. As a monoclonal antibody, it was not associated to liver toxicity and is not expected to interact with other drugs. The long half-life might improve patients' compliance. Long-term effects of CGRP block in cardiovascular, grastrointestinal and bone functions should be evaluated in ongoing trials, since CGRP is involved in multiple biological activities in the human body. Nevertheless, targeting CGRP itself allows the receptor binding with other ligands involved in several physiological functions. Thus, the long-term treatment with Fremanezumab is expected to be associated with a lower risk of severe adverse effects.
降钙素基因相关肽(CGRP)在神经源性炎症和三叉神经血管伤害性信号转导中发挥作用,因此被认为与偏头痛的病理生理学有关。新的靶向 CGRP 及其受体的分子已被开发为偏头痛特异性预防治疗药物。依洛尤单抗(fremanezumab,或 TEV-48,125,LBR-101)是一种针对 CGRP 的人源单克隆抗体,最近已被 FDA 和 EMA 批准用于临床。
本文简要讨论了降钙素家族神经递质及其相关的激活途径,并深入探讨了依洛尤单抗的化学性质、药效学、药代动力学、临床疗效和安全性,用于偏头痛的预防性治疗。
依洛尤单抗是一种偏头痛特异性药物,作为慢性和发作性偏头痛的预防性治疗是有效且安全的。作为一种单克隆抗体,它与肝毒性无关,预计不会与其他药物相互作用。长半衰期可能会提高患者的依从性。正在进行的试验应评估 CGRP 阻断对心血管、胃肠道和骨骼功能的长期影响,因为 CGRP 参与了人体的多种生物学活动。然而,靶向 CGRP 本身允许受体与其他涉及多种生理功能的配体结合。因此,长期使用依洛尤单抗预计与严重不良反应的风险较低相关。