DAY 2: JAK Inhibitors and S1P Receptor Modulators

Isabel Lopera, MD, from the Mayo Clinic, performed a retrospective review of 19 patients 16 years of age and older who were admitted for acute severe ulcerative colitis (UC) between 2023 and 2025 and treated with the JAK inhibitor upadacitinib. Mean age at hospitalization was 33.9 years and all patients had prior exposure to advanced therapy. Median C-reactive protein (CRP) levels at admission were 73.4 mg/L. On day 3 of upadacitinib, median CRP level was 34 mg/L, and 63.1% of patients showed a clinical response, defined as at least a 50% reduction in stool frequency and reduction in bleeding. The 90-day colectomy rate was 36.8% and the 90-day remission rate was 66.7%. Adverse events occurred in 21.1% of patients, with 1 thromboembolic event. Prior to the availability of JAK inhibitors, patients were more likely to proceed to colectomy; this evaluation suggests that upadacitinib is an effective and safe rescue therapy for acute severe UC. (P1191)

Remo Panaccione, MD, from the University of Calgary, reported on an analysis of data from the open-label extension of the U-ACTIVATE study, which evaluated the efficacy of upadacitinib retreatment after treatment interruption in patients with UC. A total of 223 patients received and responded to 8-week induction therapy with upadacitinib and then were re-randomized to placebo for maintenance. Of these, 112 patients lost response and 110 were enrolled into the open-label extension study. Patients received upadacitinib 15 mg once daily, which could be escalated to 30 mg once daily if needed. At week 144, 51.8% of patients remained on the lower dose and 42.7% had been escalated to the higher dose. Clinical remission at 144 weeks based on Mayo score was achieved by 76.3% of patients who remained on the lower dose and 61.1% of patients on the escalated dose. Endoscopic remission at week 144 was achieved by 33.3% of patients on the lower dose and 56.4% of patients on the escalated dose. In most patients, clinical and endoscopic efficacy was restored after restarting treatment with upadacitinib. (P5431)

Om Patel, MD, from Virtua Health System, performed a retrospective safety analysis of the JAK inhibitor tofacitinib using data from TriNetX on adults with UC who initiated treatment between 2019 and 2024. Patients who received tofacitinib were categorized by prior exposure to biologics (n=877) or no prior exposure (n=924) using propensity score matching. There was no difference between the two groups with regard to risk of UC complications, partial colectomy rates, or 6-month hospitalization rate. (P1037)

Bruce E. Sands, MS, MS, FACG, from the Icahn School of Medicine, presented the long-term efficacy of etrasimod in patients with moderately to severely active UC from the ELEVATE open-label extension study (NCT03950232). Etrasimod is an oral S1P receptor modulator; patients in the study received 2 mg once daily with endpoints assessed at 1 year and 2 years. A total of 890 patients entered the ELEVATE open-label extension, and 296 patients were included in the efficacy analysis. Mean etrasimod exposure was 120 weeks, with data available for 252 patients who received at least 1 year of treatment and 207 who received at least 2 years of treatment. Mean patient age was 43.7 years, 46.6% were female, and 73% were naive to biologics and small molecule IBD therapies. 11.2% of patients experienced any serious treatment-emergent adverse event that led to discontinuation, and there were 3 deaths judged unrelated to treatment (1 neuroendocrine tumor, 1 acute monocytic leukemia, and 1 cardiac arrest after a scheduled colectomy). Clinical response was 89.3% at year 1 and 87.6% at year 2, and clinical remission was 56.6% at year 1 and 55.2% at year 2. Symptomatic remission was 81.3% at year 1 and 78.8% at year 2. Etrasimod demonstrated durable efficacy through 2 years of treatment; data collection is ongoing for future timepoints. (P3191)