背景:炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),继续挑战治疗范式。新药类别的2期和3期临床试验推动了治疗选择的进步,特别是鞘氨醇-1-磷酸(S1P)调节剂和白介素-23(IL-23)抑制剂。
方法:这篇综述综合了2024年初进行的2期和3期临床试验的结果,重点是S1P调节剂和IL-23抑制剂对IBD管理的影响。药物如ozanimod,etrasimod,risankizumab,mirikizumab,guselkumab,和brasikumab进行了疗效和安全性评估.
结果:S1P调制器,比如ozanimod和etrasimod,有效地调节免疫细胞运输,以减少炎症和一些试验强调其在诱导和维持缓解IBD的临床有效性,强调其长期安全性和持续的治疗效果。此外,IL-23抑制剂,包括risankizumab,mirikizumab,和guselkumab,破坏关键的炎症细胞因子途径,已经在诱导和维持CD和UC缓解方面显示出显著的有效性,在多项研究中具有良好的安全性,表明它们作为管理IBD的关键组成部分的潜力。
结论:临床试验表明,S1P调节剂和IL-23抑制剂均可提供有希望的治疗效果,并保持强大的安全性。将它们定位为IBD的潜在基石治疗。尽管取得了这些进步,进一步探索长期安全性和制定个性化治疗策略对于最大化临床结局至关重要.
BACKGROUND: Inflammatory bowel disease (IBD), encompassing Crohn\'s disease (CD) and ulcerative colitis (UC), continues to challenge treatment paradigms. Advancements in therapeutic options have been have been driven by Phase 2 and 3 clinical trials of new drug classes, particularly sphingosine-1-phosphate (S1P) modulators and interleukin-23 (IL-23) inhibitors.
METHODS: This review synthesizes findings from Phase 2 and 3 clinical trials conducted up to early 2024, focusing on the impact of S1P modulators and IL-23 inhibitors on IBD management. Drugs such as ozanimod, etrasimod, risankizumab, mirikizumab, guselkumab, and brasikumab were evaluated for their efficacy and safety profiles.
RESULTS: S1P modulators, such as ozanimod and etrasimod, effectively regulate immune cell trafficking to reduce inflammation and several trials highlight their clinical effectiveness in both inducing and maintaining remission in IBD, highlighting its long-term safety and sustained therapeutic effects. Additionally, IL-23 inhibitors including risankizumab, mirikizumab, and guselkumab, which disrupt key inflammatory cytokine pathways, have already shown significant effectiveness in inducing and maintaining remission in both CD and UC, with favorable safety profiles across multiple studies, suggesting their potential as critical components in managing IBD.
CONCLUSIONS: The clinical trials indicate that both S1P modulators and IL-23 inhibitors offer promising therapeutic benefits and maintain strong safety profiles, positioning them as potential cornerstone treatments for IBD. Despite these advancements, further exploration into long-term safety and the development of personalized treatment strategies is essential for maximizing clinical outcomes.