New management strategies in ulcerative colitis: a narrative review
Nuevas estrategias de manejo en la colitis ulcerativa: Una revisión narrativa
DOI:
https://doi.org/10.22258/hgh.2026.101.283Abstract
Introduction: Ulcerative colitis is a chronic inflammatory bowel disease with high morbidity, requiring therapeutic innovations to improve clinical outcomes. Objective: To evaluate new therapeutic strategies for moderate to severe ulcerative colitis. Methods: A narrative review based on indexed scientific literature from PubMed, EMBASE, and Cochrane was conducted without language restrictions. The search was performed between January 2015 and June 2025, using keywords such as "Janus-Kinase (JAK) inhibitors", "phosphodiesterase-4 (PDE4) inhibitors", "G protein-coupled sphingosine receptor modulators", and "fecal microbiota transplantation". Results: JAK inhibitors (tofacitinib, upadacitinib) demonstrated efficacy in early clinical remission, with significant improvements in symptoms and inflammatory markers. Sphingosine modulators (ozanimod) showed potential to reduce systemic and local inflammation with a favorable safety profile. Fecal microbiota transplantation emerged as a promising therapeutic strategy, although with variable response rates. Conclusion: These therapies represent significant advances in ulcerative colitis management. However, standardization of patient selection criteria and therapeutic protocols is needed, along with longitudinal studies to assess their long-term safety and efficacy. Keywords: Colitis, Ulcerative; Inflammatory Bowel Diseases; Colonic Diseases; Therapeutics (Source: MeSH, NLM).Downloads
References
Pisani LF, Moriggi M, Gelfi C, Vecchi M, Pastorelli L. Proteomic insights on the metabolism in inflammatory bowel disease. World J Gastroenterol. 2020;26(7):696-705. DOI: 10.3748/wjg.v26.i7.696.
Salice M, Rizzello F, Calabrese C, Calandrini L, Gionchetti P. A current overview of corticosteroid use in active ulcerative colitis. Expert Rev Gastroenterol Hepatol. 2019;13(6):557-561. DOI: 10.1080/17474124.2019.1604219.
Vitello A, Maida M, Shahini E, Macaluso FS, Orlando A, Grova M, et al. Current Approaches for Monitoring of Patients with Inflammatory Bowel Diseases: A Narrative Review. J Clin Med. 2024;13(4):1008. DOI: 10.3390/jcm13041008.
Fernández-Ávila DG, Bernal-Macías S, Parra-Izquierdo V, Rincón-Riaño DN, Gutiérrez JM, Rosselli D. Prevalence of inflammatory bowel disease and related arthritis in Colombia, according to information from the Health and Social Protection Data System. Rev Colomb Reumatol. 2020;27(1):3-8. DOI: 10.1016/j.rcreu.2019.10.006.
Maconi G, Camatta D, Cannatelli R, Ferretti F, Gabrielli AC, Ardizzone S. Budesonide MMX in the treatment of ulcerative colitis: Current perspectives on efficacy and safety. Ther Clin Risk Manag. 2021;17:285-292. DOI: 10.2147/TCRM.S263835.
Yan ZX, Gao XJ, Li T, Wei B, Wang PP, Yang Y, et al. Fecal microbiota transplantation in experimental ulcerative colitis reveals associated gut microbial and host metabolic reprogramming. Appl Environ Microbiol. 2018;84(14):e00434-18. DOI: 10.1128/AEM.00434-18.
Yamamoto-Furusho JK, Fonseca-Camarillo G, Furuzawa-Carballeda J, Sarmiento-Aguilar A, Barreto-Zuñiga R, Martínez-Benitez B, et al. Caspase recruitment domain (CARD) family (CARD9, CARD10, CARD11, CARD14 and CARD15) are increased during active inflammation in patients with inflammatory bowel disease. J Inflamm (Lond). 2018;15:11. DOI: 10.1186/s12950-018-0189-4.
Moparthi L, Koch S. Wnt signaling in intestinal inflammation. Differentiation. 2019;108:24-32. DOI: 10.1016/j.diff.2019.01.002.
Serigado JM, Foulke-Abel J, Hines WC, Hanson JA, In J, Kovbasnjuk O. Ulcerative Colitis: Novel Epithelial Insights Provided by Single Cell RNA Sequencing. Front Med (Lausanne). 2022;9:868508. DOI: 10.3389/fmed.2022.868508.
Bradley CA. IBD: Tofacitinib effective in ulcerative colitis. Nat Rev Gastroenterol Hepatol. 2017;14(7):388. DOI: 10.1038/nrgastro.2017.66.
Friedman S. Tofacitinib for Ulcerative Colitis: A Promising Step Forward. N Engl J Med. 2017;376(18):1792-1793. DOI: 10.1056/NEJMe1701505.
Sandborn WJ, Su C, Sands BE, D’Haens GR, Vermeire S, Schreiber S, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017;376(18):1723-1736. DOI: 10.1056/NEJMoa1606910.
Esfahani K, Hudson M, Batist G. Tofacitinib for Refractory Immune-Related Colitis from PD-1 Therapy. N Engl J Med. 2020;382(24):2374-2375. DOI: 10.1056/NEJMc2002527.
Dai C, Jiang M, Sun MJ. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2017;377(5):496-497. DOI: 10.1056/NEJMc1707500.
Panés J, Vermeire S, Lindsay JO, Sands BE, Su C, Friedman G, et al. Tofacitinib in patients with ulcerative colitis: Health-related quality of life in phase 3 randomised controlled induction and maintenance studies. J Crohns Colitis. 2018;12(2):145-156. DOI: 10.1093/ecco-jcc/jjx133.
Hanauer S, Panaccione R, Danese S, Cheifetz A, Reinisch W, Higgins PDR, et al. Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2019;17(1):139-147. DOI: 10.1016/j.cgh.2018.07.009.
Weisshof R, Aharoni Golan M, Sossenheimer PH, El Jurdi K, Ollech JE, Pekow J, et al. Real-World Experience with Tofacitinib in IBD at a Tertiary Center. Dig Dis Sci. 2019;64(7):1945-1951. DOI: 10.1007/s10620-019-05492-y.
Patel A, Fenster M, Bader G, Dimopoulos C, Deepak P, Ungaro RC, et al. 796 Real-World Effectiveness of Tofacitinib in Ulcerative Colitis; a Multi-Center Study. Gastroenterology. 2019;156(6 Suppl 1):S168-S169. DOI: 10.1016/S0016-5085(19)37213-0.
Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399(10341):2113-2128. DOI: 10.1016/S0140-6736(22)00581-5.
Panaccione R, Danese S, Zhou W, Klaff J, Ilo D, Yao X, et al. Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Active Ulcerative Colitis Receiving 16 Weeks Extended Induction Treatment Followed by 52 Weeks Maintenance Treatment in U-ACHIEVE/U-ACCOMPLISH Trials. Am J Gastroenterol. 2022;117(Suppl):e505-e506. DOI: 10.14309/01.ajg.0000859528.76845.26.
Bu Y, Traore MDM, Zhang L, Wang L, Liu Z, Hu H, et al. A gastrointestinal locally activating Janus kinase inhibitor to treat ulcerative colitis. J Biol Chem. 2023;299(12):105467. DOI: 10.1016/j.jbc.2023.105467.
Sandborn WJ, Nguyen DD, Beattie DT, Brassil P, Krey W, Woo J, et al. Development of gut-selective pan-janus kinase inhibitor TD-1473 for ulcerative colitis: A translational medicine programme. J Crohn’s Colitis. 2020;14(9):1202-1213. DOI: 10.1093/ecco-jcc/jjaa049.
Li H, Zuo J, Tang W. Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Front Pharmacol. 2018;9:1048. DOI: 10.3389/fphar.2018.01048.
Crowley EL, Gooderham MJ. Phosphodiesterase-4 Inhibition in the Management of Psoriasis. Pharmaceutics. 2023;16(1):23. DOI: 10.3390/pharmaceutics16010023.
Wittmann M, Helliwell PS. Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases. Dermatol Ther (Heidelb). 2013;3(1):1-15. DOI: 10.1007/s13555-013-0023-0.
Sakkas LI, Mavropoulos A, Bogdanos DP. Phosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Applications, Current and Future Perspectives. Curr Med Chem. 2017;24(28):3054-3067. DOI: 10.2174/0929867324666170530093902.
Gold LS, Bagel J, Lebwohl M, Mark Jackson J, Chen R, Goncalves J, et al. Efficacy and safety of apremilast in systemic- and biologic-naive patients with moderate plaque psoriasis: 52-week results of UnVEIL. J Drugs Dermatol. 2018;17(2):221-228.
Pincelli C, Schafer PH, French LE, Augustin M, Krueger JG. Mechanisms underlying the clinical effects of apremilast for psoriasis. J Drugs Dermatol. 2018;17(8):835-840.
Ohtsuki M, Okubo Y, Komine M, Imafuku S, Day RM, Chen P, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial. J Dermatol. 2017;44(8):873-884. DOI: 10.1111/1346-8138.13829.
McIlroy J, Ianiro G, Mukhopadhya I, Hansen R, Hold GL. Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management. Aliment Pharmacol Ther. 2018;47(1):26-42. DOI: 10.1111/apt.14384.
Huson DH, Mitra S, Ruscheweyh HJ, Weber N, Schuster SC. Integrative analysis of environmental sequences using MEGAN4. Genome Res. 2011;21(9):1552-1560. DOI: 10.1101/gr.120618.111.
Varadé J, Magadán S, González-Fernández Á. Human immunology and immunotherapy: main achievements and challenges. Cell Mol Immunol. 2021;18(4):805-828. DOI: 10.1038/s41423-020-00530-6.
Sonnenberg GF, Hepworth MR. Functional interactions between innate lymphoid cells and adaptive immunity. Nat Rev Immunol. 2019;19(10):599-613. DOI: 10.1038/s41577-019-0194-8.
Li J, Glover SC. Innate Lymphoid Cells in Inflammatory Bowel Disease. Arch Immunol Ther Exp (Warsz). 2018;66(6):415-421. DOI: 10.1007/s00005-018-0519-5.
Hepworth MR, Sonnenberg GF. Regulation of the adaptive immune system by innate lymphoid cells. Curr Opin Immunol. 2014;27:75-82. DOI: 10.1016/j.coi.2014.01.013.
Candelli M, Franza L, Pignataro G, Ojetti V, Covino M, Piccioni A, et al. Interaction between lipopolysaccharide and gut microbiota in inflammatory bowel diseases. Int J Mol Sci. 2021;22(12):6242. DOI: 10.3390/ijms22126242.
Cong J, Wu D, Dai H, Ma Y, Liao C, Li L, et al. Interleukin-37 exacerbates experimental colitis in an intestinal microbiome-dependent fashion. Theranostics. 2022;12(11):5204-5219. DOI: 10.7150/thno.69616.
Gao X, Cao Q, Cheng Y, Zhao D, Wang Z, Yang H, et al. Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response. Proc Natl Acad Sci U S A. 2018;115(13):E2960-E2969. DOI: 10.1073/pnas.1720696115.
D’Amico F, Allocca M, Fiorino G. Positioning Ozanimod in Ulcerative Colitis: Restoring Leukocyte Traffic Under Control. Gastroenterology. 2022;162(6):1767-1769. DOI: 10.1053/j.gastro.2021.12.235.
Sandborn WJ, Feagan BG, D’Haens G, Wolf DC, Jovanovic I, Hanauer SB, et al. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2021;385(14):1280-1291. DOI: 10.1056/NEJMoa2033617.
Lasa JS, Olivera PA, Danese S, Peyrin-Biroulet L. Efficacy and safety of biologics and small molecule drugs for patients with moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2022;7(2):161-170. DOI: 10.1016/S2468-1253(21)00377-0.
Shivaji UN, Nardone OM, Cannatelli R, Smith SC, Ghosh S, Iacucci M. Small molecule oral targeted therapies in ulcerative colitis. Lancet Gastroenterol Hepatol. 2020;5(9):850-861. DOI: 10.1016/S2468-1253(19)30414-5.
Sands BE, D’Haens G, Panaccione R, Regueiro M, Ghosh S, Hudesman D, et al. Ozanimod in Patients With Moderate to Severe Ulcerative Colitis Naive to Advanced Therapies. Clin Gastroenterol Hepatol. 2024;22(10):2084-2095.e4. DOI: 10.1016/j.cgh.2024.03.042.
Sandborn WJ, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Liu WJ, et al. Long-Term Efficacy and Safety of Ozanimod in Moderately to Severely Active Ulcerative Colitis: Results from the Open-Label Extension of the Randomized, Phase 2 TOUCHSTONE Study. J Crohn’s Colitis. 2021;15(7):1120-1129. DOI: 10.1093/ecco-jcc/jjab012.
Dubois-Camacho K, Ottum PA, Franco-Muñoz D, De La Fuente M, Torres-Riquelme A, Díaz-Jiménez D, et al. Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology. World J Gastroenterol. 2017;23(36):6628-6638. DOI: 10.3748/wjg.v23.i36.6628.
Harris S, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Yan J, et al. Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn’s Disease. Dig Dis Sci. 2024;69(6):2044-2054. DOI: 10.1007/s10620-024-08391-z.
Tran JQ, Hartung JP, Olson AD, Mendzelevski B, Timony GA, Boehm MF, et al. Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study. Clin Pharmacol Drug Dev. 2018;7(3):263-276. DOI: 10.1002/cpdd.383.
Rowan C, Ungaro R, Mehandru S, Colombel JF. An overview of ozanimod as a therapeutic option for adults with moderate-to-severe active ulcerative colitis. Expert Opin Pharmacother. 2022;23(8):893-904. DOI: 10.1080/14656566.2022.2071605.
Surapaneni S, Yerramilli U, Bai A, Dalvie D, Brooks J, Wang X, et al. Absorption, Metabolism, and Excretion, in Vitro Pharmacology, and Clinical Pharmacokinetics of Ozanimod, a Novel Sphingosine 1-Phosphate Receptor Modulator. Drug Metab Dispos. 2021;49(5):405-419. DOI: 10.1124/dmd.120.000220.
Tran JQ, Zhang P, Ghosh A, Liu L, Syto M, Wang X, et al. Single-Dose Pharmacokinetics of Ozanimod and its Major Active Metabolites Alone and in Combination with Gemfibrozil, Itraconazole, or Rifampin in Healthy Subjects: A Randomized, Parallel-Group, Open-Label Study. Adv Ther. 2020;37(10):4381-4395. DOI: 10.1007/s12325-020-01473-0.
Danese S, Panaccione R, Abreu MT, Rubin DT, Ghosh S, Dignass A, et al. Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension. J Crohn’s Colitis. 2024;18(2):264-274. DOI: 10.1093/ecco-jcc/jjad146.
Long M, Cross R, Calkwood J, Pondel M, Pai A, Ahmad H, et al. P038 Ozanimod First-Dose Cardiac Effects in Patients with Moderately to Severely Active Ulcerative Colitis and Relapsing Multiple Sclerosis. Am J Gastroenterol. 2021;116(Suppl 1):S9-S10. DOI: 10.14309/01.ajg.0000798752.72296.f3.
Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet. 1989;1(8630):164. DOI: 10.1016/s0140-6736(89)91183-5.
Minkoff NZ, Aslam S, Medina M, Tanner-Smith EE, Zackular JP, Acra S, et al. Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile). Cochrane Database Syst Rev. 2023;4(4):CD013871. DOI: 10.1002/14651858.CD013871.
Sood A, Mahajan R, Juyal G, Midha V, Grewal CS, Mehta V, et al. Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: A real world intention-to-treat analysis. Intest Res. 2019;17(1):78-86. DOI: 10.5217/ir.2018.00089.
Costello SP, Hughes PA, Waters O, Bryant RV, Vincent AD, Blatchford P, et al. Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients with Ulcerative Colitis: A Randomized Clinical Trial. JAMA. 2019;321(2):156-164. DOI: 10.1001/jama.2018.20046.
Fuentes S, Rossen NG, Van der Spek MJ, Hartman JHA, Huuskonen L, Korpela K, et al. Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation. ISME J. 2017;11(8):1877-1889. DOI: 10.1038/ismej.2017.44.
Burrello C, Garavaglia F, Cribiù FM, Ercoli G, Lopez G, Troisi J, et al. Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells. Nat Commun. 2018;9(1):5184. DOI: 10.1038/s41467-018-07359-8.
Reinshagen M, Stallmach A. Multispenderstuhl und häufige Anwendung einer Stuhltransplantation führt zu besseren Therapieerfolgen bei Patienten mit Colitis ulcerosa. Z Gastroenterol. 2017;55(08):779-780. DOI: 10.1055/s-0043-109349.
Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, et al. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015;149(1):102-109.e6. DOI: 10.1053/j.gastro.2015.04.001.
Sood A, Mahajan R, Singh A, Midha V, Mehta V, Narang V, et al. Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients with Ulcerative Colitis: A Pilot Study. J Crohn’s Colitis. 2019;13(10):1311-1317. DOI: 10.1093/ecco-jcc/jjz060.
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