Inflammatory bowel disease commonly requires advanced therapies to induce and maintain durable remission. Sphingosine-1-phosphate receptor modulators are the latest class of orally administered small molecules that have been added to the therapeutic armamentarium for inflammatory bowel disease. These molecules reduce inflammation by sequestering lymphocytes in lymph nodes, thereby reducing immune cell trafficking to the gut. Etrasimod and ozanimod are both licensed for moderate-to-severe ulcerative colitis and have both shown superiority over placebo, with emerging data for their use in Crohn’s disease. By modulating immune cell distribution, without reducing overall immune function, they offer a highly favourable safety profile. This narrative review explores the pharmacology, safety and efficacy of sphingosine-1-phosphate receptor modulators based on clinical trials and real-world evidence and offers practical guidance on their initiation and monitoring.

Background & Aims: Patient-reported outcomes (PRO) are essential for monitoring disease activity and treatment response in inflammatory bowel disease (IBD). The conventional PRO-2 requires several days of prospective symptom recording, increasing participant burden and attrition in longitudinal research. We evaluated whether a “rapid PRO-2”, using 2 days of data collected retrospectively and prospectively in a single day, could serve as a reliable and pragmatic alternative to a 4-day PRO-2. Methods: Using data from the ongoing IBD-RESPONSE cohort (n = 684 Crohn’s disease [CD]; n = 548 ulcerative colitis [UC]), we compared 4-day PRO-2 and rapid PRO-2 scores at baseline and 14 weeks post-therapy to assess disease activity, clinical (non) response and remission. Results: At baseline, 87.1% (596/684) of CD and 88.7% (486/548) of UC patients remained in the same active/inactive disease activity category (Cohen’s kappa: CD 0.715; UC 0.762; both P < .001). At week 14, 77% (CD; 195/252) and 83.1% (UC; 193/232) remained in the same non-response/response/remission category (Cohen’s kappa: CD 0.653; UC 0.743; both P < .001). Discrepancies mainly involved adjacent category shifts (ie, between response and remission, or non-response and response), with minimal re-classification between remission and non-response (n = 7 CD and n = 2 UC). Greater symptom variability across the 4 days increased the likelihood of switching between remission and non-response (odds ratio [95% confidence interval], CD 5.0 [3.65–6.85]; UC 7.8 [5.6–11.0], both P < .001). Responsiveness to clinical change was comparable between instruments. Conclusions: The rapid PRO-2 retains essential symptom data and demonstrates strong agreement with the 4-day PRO-2, offering an alternative in longitudinal studies to minimize burden and attrition.