Puca Pierluigi, Capobianco Ivan, Coppola Gaetano, Di Vincenzo Federica, Trapani Valentina, Petito Valentina, Laterza Lucrezia, Pugliese Daniela, Lopetuso Loris Riccardo, Scaldaferri Franco
Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
IBD Unit, UOC CEMAD Centro Malattie dell'Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Int J Mol Sci. 2024 Feb 28;25(5):2789. doi: 10.3390/ijms25052789.
The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.
生物药物的出现彻底改变了炎症性肠病的治疗方式，与传统疗法相比，通过能够治疗对皮质类固醇难治的病例并减少与皮质类固醇相关的副作用，提高了缓解率和黏膜愈合率。然而，生物疗法（抗TNFα抑制剂、抗α4β7整合素和抗IL12/23）的缓解率仍然较低，在初治患者中约为40%左右，而在经治患者中更低。此外，关于耐药或反应丧失的潜在机制的了解仍然很少。治疗失败涉及多个细胞和分子决定因素；细胞因子序列中的单核苷酸多态性或人类白细胞抗原形式的遗传易感性，或炎症级联反应中涉及的细胞因子和其他分子的表达改变，起着最重要的作用。辅助机制包括肠道微生物群失调。在这篇对当前和最新文献的叙述性综述中，我们阐明了上述治疗失败的决定因素，以便为更个性化的方法铺平道路，这有助于避免不必要的治疗和毒性。
