Unità Operativa Complessa di Pneumologia, Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy.
Università Cattolica del Sacro Cuore , Rome, Italy.
Expert Opin Biol Ther. 2020 Jul;20(7):779-786. doi: 10.1080/14712598.2020.1735346. Epub 2020 Mar 2.
Pirfenidone and nintedanib have been the first agents demonstrating to slow down the progressive functional decline in patients with Idiopathic Pulmonary Fibrosis (IPF). Antibody-based therapies with precise molecular targets have been largely investigated over the last decade in IPF as alternative or complementary treatments, in the hope to ameliorate the relentless fibrotic process of IPF.
In this review, we summarize the available evidence on two groups of monoclonal antibodies tested in IPF: those directed against known fibrogenic factors and matrix components, and those developed to antagonize the inflammation and immunity pathways. While the latter have failed to demonstrate any clinical efficacy in IPF so far, the anti-CTGF pamrevlumab has been recently proved to be capable of slowing down functional decline as compared to placebo, prompting further investigation.
Despite most trials on antibody-based therapies in IPF provided so far unsatisfying results, the therapeutic development in this field should continue to be pursued to deliver a more personalized treatment approach in the future, which is not currently offered by available treatment options. A more careful trial designing and the use of valid predictive markers of response to treatment are required to enhance effectiveness of future trials.
吡非尼酮和尼达尼布是首批被证明可减缓特发性肺纤维化(IPF)患者进行性功能下降的药物。在过去十年中,针对 IPF 的替代或补充治疗,作为抗体为基础的精准靶向治疗药物在很大程度上得到了广泛研究,希望能改善 IPF 无情的纤维化进程。
在这篇综述中,我们总结了在 IPF 中测试的两组单克隆抗体的现有证据:一组针对已知的纤维生成因子和基质成分,另一组则开发用于拮抗炎症和免疫途径。虽然迄今为止,针对后者的临床试验在 IPF 中均未显示出任何临床疗效,但最近已证明抗 CTGF 的 pamrevlumab 能够与安慰剂相比减缓功能下降,从而促使进一步研究。
尽管迄今为止,针对 IPF 的抗体治疗的大多数临床试验结果均令人不满意,但该领域的治疗发展仍应继续进行,以便在未来提供目前无法通过现有治疗选择提供的更个性化的治疗方法。需要更仔细的试验设计和使用有效的治疗反应预测标志物来提高未来试验的效果。