Gomollón Fernando
IBD UNIT, Digestive Diseases Service, Hospital Clínico Universitario 'Lozano Blesa', IIS Aragón, CIBEREHD, Zaragoza, Spain.
Curr Opin Gastroenterol. 2015 Jul;31(4):290-5. doi: 10.1097/MOG.0000000000000184.
The goal is to review the most recent literature about biosimilars in inflammatory bowel disease (IBD), with emphasis on controversial regulatory issues.
Although biosimilars have been in use in Europe since 2005, the recent approval of CT-P13 (Remsima, Inflectra), a biosimilar of the reference infliximab (Remicade), by the European Medicines Agency (EMA) and several regulatory agencies has become a widely discussed topic in IBD, rheumatology, and other areas. Biologics are the main drivers of cost in current IBD units, and biosimilars can reduce prices thus increasing the availability of this type of treatment. The guidelines for evaluation of biosimilars are considerably different from those of the reference biologics, regulatory agencies relying on detailed in-vitro studies for defining 'high similarity', and requiring many fewer clinical data. 'High similarity' is considered sufficient for clinical trials, as the new molecule is demonstrated so structurally similar to the reference one that no significant difference in efficacy or safety is expected. Two trials in ankylosing spondylitis and rheumatoid arthritis gave no evidence of real difference and provided the required pharmacokinetic and PD data. The main controversy remains in the 'extrapolation' of indications, accepted by EMA but not by Health Canada. Position statements from several scientific societies and some expert's reviews have expressed concerns to the concept of extrapolation without direct IBD clinical evidence, whereas EMA experts have published detailed reviews supporting extrapolation.
Biosimilars in IBD are here to stay. New data are awaited to settle the controversy of extrapolation, but only the complex behavior of markets will show whether biosimilars fuel competition and extend access to biologics with significant cuts in drug costs.
旨在回顾关于炎症性肠病（IBD）生物类似药的最新文献，重点关注有争议的监管问题。
尽管生物类似药自2005年起就在欧洲使用，但欧洲药品管理局（EMA）及其他几家监管机构近期批准的英夫利昔单抗（类克）的生物类似药CT-P13（雷米西尤单抗、英利昔单抗），已成为IBD、风湿病学及其他领域广泛讨论的话题。生物制剂是当前IBD治疗费用的主要驱动因素，而生物类似药可降低价格，从而增加此类治疗的可及性。生物类似药的评估指南与参照生物制剂的评估指南有很大不同，监管机构依靠详细的体外研究来界定“高度相似性”，且所需的临床数据要少得多。“高度相似性”被认为足以开展临床试验，因为新分子在结构上与参照分子非常相似，预计在疗效或安全性方面不会有显著差异。两项针对强直性脊柱炎和类风湿关节炎的试验未发现实际差异，并提供了所需的药代动力学和药效学数据。主要争议仍在于适应症的“外推”，EMA认可但加拿大卫生部不认可。多个科学学会的立场声明和一些专家评论对缺乏IBD直接临床证据的外推概念表示担忧，而EMA专家发表了支持外推的详细评论。
IBD领域的生物类似药已成为现实。有待新数据来解决外推的争议，但只有复杂的市场行为才能表明生物类似药是否会促进竞争，并通过大幅降低药品成本来扩大生物制剂的可及性。
