本文旨在回顧etrasimod，一種新型的sphingosine-1-phosphate (S1P) 受體調節劑，對中重度潰瘍性結腸炎 (ulcerative colitis, UC) 的療效與安全性。Etrasimod 可調節S1P1、S1P4 和S1P5 受體，能有效抑制發炎細胞因子如tumor necrosis factor、interleukin (IL)-1、IL-6 和IL-17A，同時增強抗炎細胞因子IL-10 的活性，進而改善UC 的症狀。Etrasimod 為口服使用，每日服用一次即可。三期試驗顯示，etrasimod對於中至重度活動性UC 的誘導緩解和維持緩解均具有顯著療效。研究結果表明，在12 週和52 週時，etrasimod 組的臨床緩解率和內視鏡改善率均顯著高於安慰劑組。安全性方面，etrasimod 整體耐受性良好，嚴重不良反應罕見，常見不良反應包括貧血和頭痛。Etrasimod 是繼ozanimod 之後，第二個被美國食品藥物管理局核准用於UC 的S1P 受體調節劑。儘管目前兩者間無直接比較的證據，etrasimod 在方便性上更佳，不需逐步增加劑量且較少食物交互作用。另外，雖有間接比較的證據指出，生物製劑與小分子藥品中，upadacitinib 在臨床緩解率方面表現最好，而vedolizumab則在安全性方面表現最佳，但由於病人的個體差異，多元化的治療選擇對UC 病人至關重要。Etrasimod 提供了新的口服治療選擇，未來也需要進行更多的臨床研究和上市後監測，以進一步確定etrasimod 在UC 長期治療中的效果和安全性。

 

This article reviews etrasimod, a novel sphingosine-1-phosphate (S1P) receptor modulator, evaluating its efficacy and safety in treating moderate to severe ulcerative colitis (UC). Etrasimod regulates S1P1, S1P4, and S1P5 receptors, effectively inhibiting inflammatory cytokines such as tumor necrosis factor, interleukin (IL)-1, IL-6, and IL-17A, while enhancing the activity of the anti-inflammatory cytokine IL-10, thus improving UC symptoms. Etrasimod is administered as a once-daily oral medication. Phase III trials have demonstrated efficacy of etrasimod in induction and maintenance therapy in moderate to severe active UC. The results showed that at 12 and 52 weeks, the rates of clinical remission and endoscopic improvement in the etrasimod group were significantly higher than those in the placebo group. In terms of safety, etrasimod is generally well tolerated, with rare serious adverse events and common adverse events including anemia and headache. Etrasimod is the second S1P receptor modulator approved by the U.S. Food and Drug Administration for the treatment of moderate to severe UC, following ozanimod. Although there is no direct comparative evidence between the two, etrasimod offers greater convenience, not requiring dose escalation and having fewer food interactions. Additionally, indirect evidence suggests that among biologics and small molecule medications, upadacitinib has the best clinical remission rates, while vedolizumab shows the best safety profile. However, due to individual patient differences, diversified treatment options are crucial for UC treatment. Etrasimod provides a new oral treatment option, and further studies are needed to determine the long-term effects and safety.

 

 

Submitted for publication: 2024.2.22; Accepted for publication: 2024.4.18