塞奈吉明滴眼液在治疗眼科罕见病神经营养性角膜炎中的应用

Cenegermin Eye Drops for the Treatment of Neurotrophic Keratitis

目的探讨新药塞奈吉明滴眼液的药理学特性和治疗神经营养性角膜炎(neurotrophic keratitis, NK)的有效性和局限性,为临床用药提供参考。方法查阅国内外相关文献,对塞奈吉明滴眼液的药理学特性及在NK的治疗作用进行归纳、总结、分析。结果塞奈吉明滴眼液是一种重组人神经生长因子(recombinant human nerve growth factor, rhNGF),其结构与内源性神经生长因子(nerve growth factor, NGF)一致,眼局部使用后,可在眼部表达NGF的相关作用,包括刺激眼表伤口愈合,增加泪液产生和结膜杯状细胞密度,支持角膜神经再生等。塞奈吉明滴眼液用于NK治疗的临床试验结果表明,大部分NK患者在局部使用该药物治疗8周后,与对照品赋形剂相比,塞奈吉明滴眼液在促进角膜愈合疗效上具有显著优越性,复发率低,避免了角膜盲、溶解穿孔、眼球摘除等的后果。上市后临床研究发现,塞奈吉明滴眼液8周能显著修复角膜神经纤维丛,使角膜新生血管消退,角膜知觉和视力明显改善。无论是成人NK还是儿童NK,塞奈吉明滴眼液的疗效都相似。在治疗过程中,眼部不适症状的不良反应最明显,但都较轻微一过性可耐受,基本对治疗无影响。结论塞奈吉明滴眼液作为治疗NK的孤儿药,用于治疗成人中重度NK这种罕见眼病,于2017年欧洲批准上市,2018年在美国上市,2021年在我国也成功上市,其在中国的真实世界临床治疗数据也还有待揭晓。

OBJECTIVE To provide reference for clinical use of cenegermin eye drops by reviewing its pharmacological properties, efficacy and limitations in neurotrophic keratitis(NK). METHODS The pharmacological properties of cenegermin eye drops, its efficacy and limitations in NK were reviewed by consulting domestic and foreign literature. RESULTS Cenegermin is a recombinant human nerve growth factor(rhNGF),with the same structure as endogenous nerve growth factor. It can promote corneal wound healing, increase tear production and conjunctival goblet cell density, and support corneal nerve regeneration. Clinical registry trials have proved that cenegemin eye drops can effectively cure NK. After 8 weeks of drug treatment, compared with the control vehicle, cenegimine eye drops had significant advantages in promoting corneal healing, the recurrence rate was low, and the patients avoided the consequence of corneal blind, lysis, perforation and enucleation. In post-marketing clinical trial, after one duration of treatment of 8 weeks, cenegermin eye drops significantly repaired corneal nerve plexus and regressed the corneal neovascularization, with corneal sensitivity and visual acuity improvement. Cenegermin eye drops can be used for treatment in pediatric patients with neurotrophic keratopathy. The most obvious adverse reactions of the drug are eye discomfort. These adverse reactions are relatively mild, transient and tolerable, and have no adverse effects on the treatment. CONCLUSION As an orphan drug for NK, cenegemin eye drops is successfully marketed in China in 2021 for the treatment of moderate and severe NK in adults. Its real world treatment efficacy in China is being collected and will be published in the future.