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Review

Novel Therapeutic Options for People with Ulcerative Colitis: An Update on Recent Developments with Janus Kinase (JAK) Inhibitors

, , ORCID Icon, &
Pages 131-139 | Published online: 05 May 2020

References

  • Ordas I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380(9853):1606–1619. doi:10.1016/S0140-6736(12)60150-0
  • Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380(9853):1590–1605. doi:10.1016/S0140-6736(12)60026-9
  • Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427–434. doi:10.1038/nature06005
  • Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol. 2008;8(6):458–466. doi:10.1038/nri2340
  • Neurath MF, Weigmann B, Finotto S, et al. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and crohn’s disease. J Exp Med. 2002;195(9):1129–1143. doi:10.1084/jem.20011956
  • Fuss IJ, Neurath M, Boirivant M, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157(3):1261–1270.
  • Marafini I, Angelucci E, Pallone F, et al. The IL-12/23/STAT axis as a therapeutic target in inflammatory bowel disease: mechanisms and evidence in man. Dig Dis. 2015;33(Suppl 1):113–119. doi:10.1159/000437106
  • Monteleone G, Biancone L, Marasco R, et al. Interleukin 12 is expressed and actively released by crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology. 1997;112(4):1169–1178. doi:10.1016/S0016-5085(97)70128-8
  • Monteleone G, Parrello T, Luzza F, et al. Response of human intestinal lamina propria T lymphocytes to interleukin 12: additive effects of interleukin 15 and 7. Gut. 1998;43(5):620–628. doi:10.1136/gut.43.5.620
  • Macdonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science. 2005;307(5717):1920–1925. doi:10.1126/science.1106442
  • Fuss IJ, Heller F, Boirivant M, et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004;113(10):1490–1497. doi:10.1172/JCI19836
  • Heller F, Florian P, Bojarski C, et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology. 2005;129(2):550–564. doi:10.1016/j.gastro.2005.05.002
  • Nalleweg N, Chiriac MT, Podstawa E, et al. IL-9 and its receptor are predominantly involved in the pathogenesis of UC. Gut. 2015;64(5):743–755. doi:10.1136/gutjnl-2013-305947
  • Weaver CT, Hatton RD, Mangan PR, et al. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007;25:821–852. doi:10.1146/annurev.immunol.25.022106.141557
  • Weaver CT, Elson CO, Fouser LA, et al. The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annu Rev Pathol. 2013;8:477–512. doi:10.1146/annurev-pathol-011110-130318
  • Bogaert S, Laukens D, Peeters H, et al. Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease. BMC Immunol. 2010;11:61. doi:10.1186/1471-2172-11-61
  • Troncone E, Marafini I, Pallone F, et al. Th17 cytokines in inflammatory bowel diseases: discerning the good from the bad. Int Rev Immunol. 2013;32(5–6):526–533. doi:10.3109/08830185.2013.823421
  • Monteleone G, Pallone F, MacDonald TT. Interleukin-21: a critical regulator of the balance between effector and regulatory T-cell responses. Trends Immunol. 2008;29(6):290–294. doi:10.1016/j.it.2008.02.008
  • Fina D, Sarra M, Fantini MC, et al. Regulation of gut inflammation and th17 cell response by interleukin-21. Gastroenterology. 2008;134(4):1038–1048. doi:10.1053/j.gastro.2008.01.041
  • Monteleone G, Monteleone I, Fina D, et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in crohn’s disease. Gastroenterology. 2005;128(3):687–694. doi:10.1053/j.gastro.2004.12.042
  • Caruso R, Fina D, Peluso I, et al. A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells. Gastroenterology. 2007;132(1):166–175. doi:10.1053/j.gastro.2006.09.053
  • Troncone E, Monteleone G. The safety of non-biological treatments in ulcerative colitis. Expert Opin Drug Saf. 2017;16(7):779–789. doi:10.1080/14740338.2017.1340936
  • Harbord M, Eliakim R, Bettenworth D, et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management. J Crohns Colitis. 2017;11(7):769–784.
  • Cote-Daigneault J, Bouin M, Lahaie R, et al. Biologics in inflammatory bowel disease: what are the data? United European Gastroenterol J. 2015;3(5):419–428. doi:10.1177/2050640615590302
  • Gisbert JP, Panes J. Loss of response and requirement of infliximab dose intensification in crohn’s disease: a review. Am J Gastroenterol. 2009;104(3):760–767. doi:10.1038/ajg.2008.88
  • Qiu Y, Chen BL, Mao R, et al. Systematic review with meta-analysis: loss of response and requirement of anti-TNFalpha dose intensification in crohn’s disease. J Gastroenterol. 2017;52(5):535–554. doi:10.1007/s00535-017-1324-3
  • Vermeire S, Gils A, Accossato P, et al. Immunogenicity of biologics in inflammatory bowel disease. Therap Adv Gastroenterol. 2018;11:1756283X17750355. doi:10.1177/1756283X17750355
  • Nyboe Andersen N, Pasternak B, Friis-Moller N, et al. Association between tumour necrosis factor-alpha inhibitors and risk of serious infections in people with inflammatory bowel disease: nationwide Danish cohort study. BMJ. 2015;350:h2809. doi:10.1136/bmj.h2809
  • Biancone L, Annese V, Ardizzone S, et al. Safety of treatments for inflammatory bowel disease: clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis. 2017;49(4):338–358. doi:10.1016/j.dld.2017.01.141
  • Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369(8):699–710. doi:10.1056/NEJMoa1215734
  • Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2019;381(13):1201–1214. doi:10.1056/NEJMoa1900750
  • Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for crohn’s disease. N Engl J Med. 2016;375(20):1946–1960. doi:10.1056/NEJMoa1602773
  • Pagnini C, Pizarro TT, Cominelli F. Novel pharmacological therapy in inflammatory bowel diseases: beyond anti-tumor necrosis factor. Front Pharmacol. 2019;10:671. doi:10.3389/fphar.2019.00671
  • Olivera P, Danese S, Peyrin-Biroulet L. Next generation of small molecules in inflammatory bowel disease. Gut. 2017;66(2):199–209. doi:10.1136/gutjnl-2016-312912
  • Sandborn WJ, Feagan BG, Wolf DC, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016;374(18):1754–1762.
  • Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376(18):1723–1736. doi:10.1056/NEJMoa1606910
  • Bevivino G, Monteleone G. Advances in understanding the role of cytokines in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2018;12(9):907–915. doi:10.1080/17474124.2018.1503053
  • Babon JJ, Lucet IS, Murphy JM, et al. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462(1):1–13. doi:10.1042/BJ20140712
  • Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004;117(Pt 8):1281–1283. doi:10.1242/jcs.00963
  • Soendergaard C, Bergenheim FH, Bjerrum JT, et al. Targeting JAK-STAT signal transduction in IBD. Pharmacol Ther. 2018;192:100–111. doi:10.1016/j.pharmthera.2018.07.003
  • Marafini I, Sedda S, Dinallo V, et al. Inflammatory cytokines: from discoveries to therapies in IBD. Expert Opin Biol Ther. 2019;19(11):1207–1217. doi:10.1080/14712598.2019.1652267
  • Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014;14(5):329–342. doi:10.1038/nri3661
  • Flanagan ME, Blumenkopf TA, Brissette WH, et al. Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection. J Med Chem. 2010;53(24):8468–8484. doi:10.1021/jm1004286
  • Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012;367(7):616–624. doi:10.1056/NEJMoa1112168
  • Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317(26):1625–1629. doi:10.1056/NEJM198712243172603
  • Hanauer S, Panaccione R, Danese S, 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
  • Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/xeljanz. Accessed March 06, 2020.
  • Panes J, Vermeire S, Lindsay JO, 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
  • Weisshof R, Aharoni Golan M, Sossenheimer PH, 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
  • Lair-Mehiri L, Stefanescu C, Vaysse T, et al. Real-world evidence of tofacitinib effectiveness and safety in patients with refractory ulcerative colitis. Dig Liver Dis. 2020;52(3):268–273.
  • Sands BE, Armuzzi A, Marshall JK, et al. Efficacy and safety of tofacitinib dose de-escalation and dose escalation for patients with ulcerative colitis: results from OCTAVE open. Aliment Pharmacol Ther. 2020;51(2):271–280. doi:10.1111/apt.15555
  • Wollenhaupt J, Silverfield J, Lee EB, et al. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. J Rheumatol. 2014;41(5):837–852. doi:10.3899/jrheum.130683
  • Yamanaka H, Tanaka Y, Takeuchi T, et al. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study. Arthritis Res Ther. 2016;18:34. doi:10.1186/s13075-016-0932-2
  • Bissonnette R, Iversen L, Sofen H, et al. Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2015;172(5):1395–1406. doi:10.1111/bjd.13551
  • Bachelez H, van de Kerkhof PC, Strohal R, et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet. 2015;386(9993):552–561. doi:10.1016/S0140-6736(14)62113-9
  • Winthrop KL, Melmed GY, Vermeire S, et al. Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib. Inflamm Bowel Dis. 2018;24(10):2258–2265. doi:10.1093/ibd/izy131
  • Sandborn WJ, Panes J, Sands BE, et al. Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme. Aliment Pharmacol Ther. 2019;50(10):1068–1076. doi:10.1111/apt.15514
  • Sands BE, Taub PR, Armuzzi A, et al. Tofacitinib treatment is associated with modest and reversible increases in serum lipids in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2020;18(1):123–32 e3. doi:10.1016/j.cgh.2019.04.059
  • Olivera P, Lasa J, Bonovas S, et al. Safety of Janus kinase inhibitors in patients with inflammatory bowel diseases or other immune-mediated diseases: a systematic review and meta-analysis. Gastroenterology. 2020. doi:10.1053/j.gastro.2020.01.001
  • Mahadevan U, Dubinsky MC, Su C, et al. Outcomes of pregnancies with maternal/paternal exposure in the tofacitinib safety databases for ulcerative colitis. Inflamm Bowel Dis. 2018;24(12):2494–2500. doi:10.1093/ibd/izy160
  • Ferrante M, Sabino J. Efficacy of anti-JAK inhibitors in ulcerative colitis. J Crohns Colitis. 2019. doi:10.1093/ecco-jcc/jjz202
  • Hamaguchi H, Amano Y, Moritomo A, et al. Discovery and structural characterization of peficitinib (ASP015K) as a novel and potent JAK inhibitor. Bioorg Med Chem. 2018;26(18):4971–4983. doi:10.1016/j.bmc.2018.08.005
  • Sands BE, Sandborn WJ, Feagan BG, et al. 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
  • Ma C, Lee JK, Mitra AR, et al. Systematic review with meta-analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease. Aliment Pharmacol Ther. 2019;50(1):5–23. doi:10.1111/apt.15297
  • Sandborn WJ, Panés J, Schreiber S, et al. Efficacy and safety of upadacitinib as an induction therapy for patients with moderately-to-severely active ulcerative colitis: data from the phase 2b study U-ACHIEVE. Presented at United European Gastroenteroology week 2018; 2018; Vienna.
  • Singh S, Fumery M, Sandborn WJ, et al. Systematic review with network meta-analysis: first- and second-line pharmacotherapy for moderate-severe ulcerative colitis. Aliment Pharmacol Ther. 2018;47(2):162–175. doi:10.1111/apt.14422
  • Fiorino G, Caprioli F, Daperno M, et al. Use of biosimilars in inflammatory bowel disease: a position update of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis. 2019;51(5):632–639. doi:10.1016/j.dld.2019.02.004
  • Cunningham AL, Lal H, Kovac M, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019–1032.
  • Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087–2096. doi:10.1056/NEJMoa1501184
  • Colombel JF. Herpes zoster in patients receiving JAK inhibitors for ulcerative colitis: mechanism, epidemiology, management, and prevention. Inflamm Bowel Dis. 2018;24(10):2173–2182. doi:10.1093/ibd/izy150
  • Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-boxed-warning-about-increased-risk-blood-clots-and-death-higher-dose-arthritis-and. Accessed August 28, 2019.
  • Available from: https://www.ema.europa.eu/en/news/ema-confirms-xeljanz-be-used-caution-patients-high-risk-blood-clots. Accessed November 15, 2019.
  • O’Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36(4):542–550. doi:10.1016/j.immuni.2012.03.014
  • Meyer SC, Keller MD, Woods BA, et al. Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis. Blood. 2014;124(14):2280–2284.
  • Nosaka T, van Deursen JM, Tripp RA, et al. Defective lymphoid development in mice lacking Jak3. Science. 1995;270(5237):800–802. doi:10.1126/science.270.5237.800