This article is for informational purposes only and does not constitute medical advice. Clinical trial eligibility and availability vary. Always consult a qualified healthcare professional before making any medical decisions or considering participation in a clinical trial.
Summary
Ulcerative colitis (UC) treatment has expanded dramatically from its corticosteroid-and-aminosalicylate origins. In 2026, multiple new drug classes have reached approval or late-stage trials: S1P receptor modulators (ozanimod, etrasimod), JAK inhibitors with gut selectivity (upadacitinib, filgotinib), IL-23 inhibitors (mirikizumab, risankizumab), and fecal microbiota transplantation trials. The challenge now is selecting the right treatment for individual patients — and trials are increasingly focused on precision approaches and combination strategies.
S1P Receptor Modulators: Ozanimod and Etrasimod
Sphingosine-1-phosphate (S1P) receptor modulators work by trapping lymphocytes in lymph nodes, reducing their trafficking to the inflamed intestinal mucosa. Unlike biologics, they are oral drugs — a significant advantage for many patients.
Ozanimod (Zeposia, Bristol Myers Squibb) was approved for moderate-to-severe UC in 2021. The TRUE NORTH Phase 3 trial showed clinical remission in 18.4% at 10 weeks and 37% at 52 weeks, with an endoscopic improvement rate of 45.7% at one year. Long-term extension data now available at 3 years show sustained remission rates and a favorable cardiovascular safety profile — unlike earlier S1P modulators, ozanimod has minimal effect on heart rate.
Etrasimod (Velsipity, Pfizer) received FDA approval in 2023 for moderately to severely active UC. The ELEVATE UC 52 and ELEVATE UC 12 trials demonstrated remission rates of 32.1% and 24.8% at 52 and 12 weeks respectively. Etrasimod selectively targets S1P1, S1P4, and S1P5 receptors. Current trials are evaluating etrasimod in adolescents with UC and in combination with biologic therapy for patients with inadequate response to either alone.
JAK Inhibitors: Upadacitinib and Beyond
Janus kinase (JAK) inhibitors block intracellular cytokine signaling pathways involved in intestinal inflammation. Tofacitinib was the first JAK inhibitor approved for UC, but carries cardiovascular and thromboembolic risks that limit its use. Newer, more selective JAK inhibitors aim to maintain efficacy with improved safety.
Upadacitinib (Rinvoq, AbbVie) is a selective JAK1 inhibitor approved for UC in 2022. The U-ACHIEVE induction trials showed clinical remission in 26.1% (45 mg dose) at 8 weeks for biologic-naive patients and 19.5% for biologic-experienced patients — among the highest remission rates seen in UC trials. The U-ACHIEVE maintenance trial showed 42% remission at 52 weeks. Upadacitinib carries an FDA boxed warning for serious cardiovascular events, malignancy, and thrombosis, particularly in patients over 50 with cardiovascular risk factors.
Filgotinib (Jyseleca) is approved in Europe for UC and is in ongoing trials examining long-term safety and use in combination with biologic agents for patients who are partially responding to monotherapy.
IL-23 Inhibitors: Mirikizumab and Risankizumab
Interleukin-23 is a key driver of intestinal inflammation in UC and Crohn's disease. While IL-12/23 inhibitors (ustekinumab) and IL-17 inhibitors have been effective in Crohn's, selective IL-23p19 inhibitors are emerging as highly effective options for UC specifically.
Mirikizumab (Omvoh, Eli Lilly) was approved for UC in 2023. The LUCENT-1 and LUCENT-2 trials showed clinical remission in 24.2% at induction and 49.9% at 52 weeks of maintenance, with high rates of endoscopic and histologic remission. Notably, mirikizumab showed efficacy in biologic-experienced patients, a population with historically poor response rates.
Risankizumab (Skyrizi, AbbVie), approved for Crohn's disease, completed Phase 3 trials for UC (INSPIRE and COMMAND) with results reported in 2024–2025, confirming similar efficacy in UC. Head-to-head trials comparing mirikizumab and risankizumab are in development.
Fecal Microbiota Transplantation for UC
Fecal microbiota transplantation (FMT) — transferring intestinal bacteria from healthy donors to UC patients — is based on the observation that UC patients have reduced microbial diversity and altered microbiome composition. Multiple randomized controlled trials have now been published.
The FOCUS and TOPF trials showed FMT (via colonoscopic delivery of multi-donor preparations) achieved clinical remission in 32–35% of patients with active UC vs. 9–10% for placebo. Donor selection appears critical: "super-donors" with specific microbiome characteristics produce better outcomes. SER-287 (a capsule-based FMT product from Seres Therapeutics) failed a Phase 2b trial, but next-generation manufactured microbiome products (including Vedanta Biosciences VE303) targeting specific bacterial communities are in ongoing Phase 2 trials. FMT remains investigational for UC in most countries.
Key Takeaways
- Ozanimod and etrasimod offer oral alternatives to injections/infusions, with sustained remission in roughly one-third of patients at one year.
- Upadacitinib has among the highest induction remission rates of any UC drug but carries important cardiovascular/malignancy warnings for older patients.
- Mirikizumab and risankizumab (selective IL-23 blockers) show strong efficacy in both biologic-naive and biologic-experienced UC populations.
- FMT via colonoscopic multi-donor delivery shows ~32–35% clinical remission in trials; capsule-based products are in active development.
- Combination biologic + small molecule strategies are being explored for patients with incomplete response to monotherapy.