Allergan/AbbVie, Irvine, CA, USA.
University of California, Irvine, CA, USA.
Medicine (Baltimore). 2023 Jul 1;102(S1):e32373. doi: 10.1097/MD.0000000000032373.
Clinical use of onabotulinumtoxinA evolved based on strategic, hypothesis-driven applications, as well as serendipitous observations by physicians and patients. The success of onabotulinumtoxinA in blepharospasm and strabismus led to its study in other head and neck dystonias, followed by limb dystonia, tremor, and spasticity. The aesthetic use of onabotulinumtoxinA followed initial reports from patients of improved facial lines after injections for facial dystonias and hemifacial spasm. Although patients with dystonias and spasticity regularly reported that their local pain improved after injections, onabotulinumtoxinA was not systematically explored for chronic migraine until patients began reporting headache improvements following aesthetic injections. Clinicians began assessing onabotulinumtoxinA for facial sweating and hyperhidrosis based on its inhibition of acetylcholine from sympathetic cholinergic nerves. Yet another line of research grew out of injections for laryngeal dystonia, whereby clinicians began to explore other sphincters in the gastrointestinal tract and eventually to treatment of pelvic sphincters; many of these sphincters are innervated by autonomic nerves. Additional investigations in other autonomically mediated conditions were conducted, including overactive bladder and neurogenic detrusor overactivity, achalasia, obesity, and postoperative atrial fibrillation. The study of onabotulinumtoxinA for depression also grew out of the cosmetic experience and the observation that relaxing facial muscle contractions associated with negative emotions may improve mood. For approved indications, the safety profile of onabotulinumtoxinA has been demonstrated in the formal development programs and post-marketing reports. Over time, evidence has accumulated suggesting clinical manifestations of systemic effects, albeit uncommon, particularly with high doses and in vulnerable populations. Although onabotulinumtoxinA is approved for approximately 26 indications across multiple local regions, there are 15 primary indication uses that have been approved in most regions, including the United States, Europe, South America, and Asia. This review describes many uses for which AbbVie has not sought and/or received regulatory approval and are mentioned for historical context only.
肉毒毒素 A 的临床应用是基于策略、假设驱动的应用，以及医生和患者的偶然观察。肉毒毒素 A 在眼睑痉挛和斜视中的成功应用导致其在其他头颈部肌张力障碍中的研究，随后是肢体肌张力障碍、震颤和痉挛。肉毒毒素 A 的美学应用紧随初始报告，患者在面部肌张力障碍和半面痉挛注射后报告面部线条改善。尽管肌张力障碍和痉挛患者经常报告注射后局部疼痛改善，但直到患者在美学注射后开始报告头痛改善，肉毒毒素 A 才被系统地探索用于慢性偏头痛。临床医生开始评估肉毒毒素 A 对面部出汗和多汗症的作用，基于其抑制来自交感胆碱能神经的乙酰胆碱。另一条研究线源于喉肌张力障碍的注射，临床医生开始探索胃肠道中的其他括约肌，最终治疗骨盆括约肌；这些括约肌中的许多都由自主神经支配。对其他自主介导的疾病进行了额外的研究，包括膀胱过度活动症和神经源性逼尿肌过度活动症、贲门失弛缓症、肥胖症和术后心房颤动。肉毒毒素 A 治疗抑郁症的研究也源于美容经验和观察，即放松与负面情绪相关的面部肌肉收缩可能会改善情绪。对于已批准的适应症，肉毒毒素 A 的安全性已在正式开发计划和上市后报告中得到证明。随着时间的推移，证据逐渐积累表明存在全身作用的临床表现，尽管不常见，但特别是在高剂量和脆弱人群中。尽管肉毒毒素 A 已在多个地区获得约 26 种适应症的批准，但在大多数地区（包括美国、欧洲、南美洲和亚洲），有 15 种主要适应症已获得批准。本综述描述了 AbbVie 尚未寻求和/或获得监管批准的许多用途，仅为历史背景而提及。
