BACKGROUND:Anti-tumour necrosis factor (anti-TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13; however, some uncertainty exists regarding their pharmacology in IBD. AIM:To review the literature on anti-TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD. METHODS:A PubMed literature search was performed using the following terms individually or in combination: 'biosimilars,' 'CT-P13,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'anti-TNFα therapy,' 'infliximab,' 'adalimumab,' 'pharmacokinetics,' 'immunogenicity.' RESULTS:Bioequivalence of CT-P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT-P13 in IBD come from small post-marketing registries and case series with a relatively short-term follow-up period and suggest comparable efficacy and safety to infliximab. Inter- and intra-individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross-reactivity of anti-drug antibodies and whether similar exposure-response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably. CONCLUSIONS:It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post-marketing studies and pharmacovigilance are warranted in the coming years.

译文

背景:抗肿瘤坏死因子(TNF)单克隆抗体已显示出在炎症性肠病(IBD)中的功效。由于这些疗法失去专利保护,因此正在开发原始产品的生物仿制药,例如英夫利昔单抗生物仿制药CT-P13;然而,关于它们在IBD中的药理学存在一些不确定性。
目的:回顾有关抗TNF生物仿制药的文献,重点关注与它们在IBD中的使用有关的药代动力学,药效学性质和比较有效性。
方法:使用以下术语单独或组合使用PubMed文献进行搜索:“生物仿制药”,“ CT-P13”,“克罗恩氏病”,“炎症性肠病”,“溃疡性结肠炎”,“抗TNFα治疗” “英夫利昔单抗”,“阿达木单抗”,“药代动力学”,“免疫原性”。
结果:强直性脊柱炎(AS)和类风湿关节炎(RA)的治疗等效性均显示出CT-P13和英夫利昔单抗的生物等效性。 IBD中CT-P13的初步结果来自小型上市后注册机构和系列病例,且随访时间相对较短,提示其疗效和安全性与英夫利昔单抗相当。对于原始分子,个体间和个体内的暴露和反应差异是众所周知的,但是RA与IBD相比,给药方案和伴随药物有所不同,从而限制了将RA中某些药理学数据转化为IBD的能力。关于抗药物抗体的交叉反应性存在不确定性,对于生物仿制药是否会观察到相似的暴露-反应关系,治疗药物监测的功效阈值可以互换使用。
结论:由于生物仿制药可节省成本且具有可比的功效,因此可能会被广泛用于IBD的治疗。尽管如此,未来几年仍需要进行可靠的上市后研究和药物警戒。

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