Emerging Therapies for Ulcerative Colitis: Updates from Recent Clinical Trials

Overview

Journal Clin Exp Gastroenterol

Publisher Dove Medical Press

Specialty Gastroenterology

Date 2023 Aug 23

PMID 37609124

Authors

Turki AlAmeel

Abdulelah AlMutairdi

Badr Al-Bawardy

Affiliations

Soon will be listed here.

Abstract

Ulcerative colitis (UC) is a chronic and progressive inflammatory disorder that affects the colon. The advent of advanced therapies such as biologic agents and small molecules has revolutionized the management of UC. Despite the expanding therapeutic armamentarium of advanced therapies to treat UC, the overall net remission rates and durability of currently available agents are relatively low. This highlights the need for further drug development and more innovative clinical trial design. There are currently multiple emerging agents in the pipeline for the management of UC. This includes agents with alternative routes of administration such as oral or subcutaneous tumor necrosis factor inhibitors or novel mechanisms of action such as toll-like receptor 9 (TLR9) agonist cobitolimod and phosphodiesterase 4 inhibitor apremilast. In this review, we will highlight novel and emerging advanced therapies currently in the pipeline for the management of UC.

Citing Articles

Coix Seed Oil Alleviates DSS-Induced Ulcerative Colitis via Intestinal Barrier Repair and Ferroptosis Regulation.

Zeng Y, Li N, Deng B, Gu Y, Lu S, Liu Y J Inflamm Res. 2025; 18:2557-2581.

PMID: 39995826 PMC: 11849537. DOI: 10.2147/JIR.S501745.

Exploring the Connections: Autophagy, Gut Microbiota, and Inflammatory Bowel Disease Pathogenesis.

Subramanian A, J A, T T, Kumarasamy V, Begum M, Sekar M J Inflamm Res. 2024; 17:10453-10470.

PMID: 39654856 PMC: 11626960. DOI: 10.2147/JIR.S483958.

Inflammatory bowel disease training assessment of gastroenterology fellows in Saudi Arabia.

AlDhneem H, AlMutairdi A, Attamimi M, Mosli M, AlAmeel T, Al-Bawardy B Saudi J Gastroenterol. 2024; 30(4):260-265.

PMID: 38841910 PMC: 11379256. DOI: 10.4103/sjg.sjg_19_24.

Selecting first-line advanced therapy for ulcerative colitis: A clinical application of personalized medicine.

Mukhtar M, Mosli M Saudi J Gastroenterol. 2024; 30(3):126-137.

PMID: 38597333 PMC: 11198921. DOI: 10.4103/sjg.sjg_427_23.

Efficacy and safety of moxibustion for ulcerative colitis: protocol for a systematic review and meta-analysis.

Li Y, Zhou W, Chen W, Deng B, You J BMJ Open. 2024; 14(3):e078878.

PMID: 38503422 PMC: 10952919. DOI: 10.1136/bmjopen-2023-078878.

References

Danese S, Ferrante M, Feagan B, Peyrin-Biroulet L, Hibi T, Sandborn W . Rapid and Sustained Symptom Relief in Patients With Ulcerative Colitis Treated With Filgotinib: Data From the Phase 2b/3 SELECTION Trial. Am J Gastroenterol. 2022; 118(1):138-147. PMC: 9810009. DOI: 10.14309/ajg.0000000000001979. View

Sugahara K, Maeda Y, Shimano K, Mogami A, Kataoka H, Ogawa K . Amiselimod, a novel sphingosine 1-phosphate receptor-1 modulator, has potent therapeutic efficacy for autoimmune diseases, with low bradycardia risk. Br J Pharmacol. 2016; 174(1):15-27. PMC: 5221453. DOI: 10.1111/bph.13641. View

DHaens G, Panaccione R, Baert F, Bossuyt P, Colombel J, Danese S . Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. Lancet. 2022; 399(10340):2015-2030. DOI: 10.1016/S0140-6736(22)00467-6. View

Sands B, Peyrin-Biroulet L, Loftus Jr E, Danese S, Colombel J, Toruner M . Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med. 2019; 381(13):1215-1226. DOI: 10.1056/NEJMoa1905725. View

Krugliak Cleveland N, Torres J, Rubin D . What Does Disease Progression Look Like in Ulcerative Colitis, and How Might It Be Prevented?. Gastroenterology. 2022; 162(5):1396-1408. DOI: 10.1053/j.gastro.2022.01.023. View

Bhol K, Tracey D, Lemos B, Lyng G, Erlich E, Keane D . AVX-470: a novel oral anti-TNF antibody with therapeutic potential in inflammatory bowel disease. Inflamm Bowel Dis. 2013; 19(11):2273-81. PMC: 3894572. DOI: 10.1097/MIB.0b013e3182a11958. View

Burr N, Gracie D, Black C, Ford A . Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis. Gut. 2021; . DOI: 10.1136/gutjnl-2021-326390. View

Sandborn W, Danese S, Leszczyszyn J, Romatowski J, Altintas E, Peeva E . Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study. Clin Gastroenterol Hepatol. 2023; 21(10):2616-2628.e7. DOI: 10.1016/j.cgh.2022.12.029. View

Sands B, Sandborn W, Feagan B, Lichtenstein G, Zhang H, Strauss R . Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study. J Crohns Colitis. 2018; 12(10):1158-1169. DOI: 10.1093/ecco-jcc/jjy085. View

10.

. Efficacy and Safety of Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 Inhibitor, in Patients With Moderately to Severely Active Ulcerative Colitis: 12-Week Results From the Phase 2 LATTICE-UC Study. Gastroenterol Hepatol (N Y). 2023; 18(7 Suppl 2):6. PMC: 9671062. View

11.

DHaens G, van Deventer S . 25 years of anti-TNF treatment for inflammatory bowel disease: lessons from the past and a look to the future. Gut. 2021; 70(7):1396-1405. DOI: 10.1136/gutjnl-2019-320022. View

12.

Sandborn W, Feagan B, DHaens G, Wolf D, Jovanovic I, Hanauer S . Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2021; 385(14):1280-1291. DOI: 10.1056/NEJMoa2033617. View

13.

Pan W, Kock K, Rees W, Sullivan B, Evangelista C, Yen M . Clinical pharmacology of AMG 181, a gut-specific human anti-α4β7 monoclonal antibody, for treating inflammatory bowel diseases. Br J Clin Pharmacol. 2014; 78(6):1315-33. PMC: 4256621. DOI: 10.1111/bcp.12418. View

14.

Chen B, Zhong J, Li X, Pan F, Ding Y, Zhang Y . Efficacy and Safety of Ivarmacitinib in Patients With Moderate-to-Severe, Active, Ulcerative Colitis: A Phase II Study. Gastroenterology. 2022; 163(6):1555-1568. DOI: 10.1053/j.gastro.2022.08.007. View

15.

Roda G, Narula N, Pinotti R, Skamnelos A, Katsanos K, Ungaro R . Systematic review with meta-analysis: proximal disease extension in limited ulcerative colitis. Aliment Pharmacol Ther. 2017; 45(12):1481-1492. PMC: 6350510. DOI: 10.1111/apt.14063. View

16.

Goettel J, Kotlarz D, Emani R, Canavan J, Konnikova L, Illig D . Low-Dose Interleukin-2 Ameliorates Colitis in a Preclinical Humanized Mouse Model. Cell Mol Gastroenterol Hepatol. 2019; 8(2):193-195. PMC: 6661391. DOI: 10.1016/j.jcmgh.2019.05.001. View

17.

Ungaro R, Mehandru S, Allen P, Peyrin-Biroulet L, Colombel J . Ulcerative colitis. Lancet. 2016; 389(10080):1756-1770. PMC: 6487890. DOI: 10.1016/S0140-6736(16)32126-2. View

18.

Feagan B, Danese S, Loftus Jr E, Vermeire S, Schreiber S, Ritter T . Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet. 2021; 397(10292):2372-2384. DOI: 10.1016/S0140-6736(21)00666-8. View

19.

Vermeire S, Chiorean M, Panes J, Peyrin-Biroulet L, Zhang J, Sands B . Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study. J Crohns Colitis. 2021; 15(6):950-959. PMC: 8218705. DOI: 10.1093/ecco-jcc/jjab016. View

20.

Vermeire S, Sands B, Tilg H, Tulassay Z, Kempinski R, Danese S . ABX464 (obefazimod) for moderate-to-severe, active ulcerative colitis: a phase 2b, double-blind, randomised, placebo-controlled induction trial and 48 week, open-label extension. Lancet Gastroenterol Hepatol. 2022; 7(11):1024-1035. DOI: 10.1016/S2468-1253(22)00233-3. View