JAK selectivity: more precision less troubles

References

• Van Assche G, Dignass A, Panes J, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohns Colitis. 2010;4(1):7–27.
   PubMed Web of Science ®Google Scholar
• 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 Crohn’s Colitis. 2017;11(7):769–784.
   Google Scholar
• Geremia A, Biancheri P, Allan P, et al. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):3–10.
   PubMed Web of Science ®Google Scholar
• Aaronson DS, Horvath CM. A road map for those who don’t know JAK-STAT. Science. 2002;296(5573):1653–1655.
   PubMed Web of Science ®Google Scholar
• Shuai K, Nat LB. Regulation of JAK-STAT signaling in the immune system. Rev Immunol. 2003;3(11):900–911.
   Google Scholar
• Olivera P, Danese S, Peyrin-Biroulet L. Next generation of small molecules in inflammatory bowel disease. Gut. 2017;66(2):199–209.
   PubMed Web of Science ®Google Scholar
• Choy EH. Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology. 2018;10:1.
   Google Scholar
• Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004;117(Pt 8):1281–1283.
   PubMed Web of Science ®Google Scholar
• Fernández-Clotet A, Castro-Poceiro J, Panés J, et al. The most promising agents in the IBD pipeline? Curr Pharm Des. 2019;25(1):32–40.
   PubMed Web of Science ®Google Scholar
• Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253–1262.
   PubMed Web of Science ®Google Scholar
• Boland BS, Vermeire S. Janus kinase antagonists and other novel small molecules for the treatment of crohn’s disease. Gastroenterol Clin North Am. 2017;46:627–644.
   PubMed Web of Science ®Google Scholar
• Ghoreschi K, Laurence A, O’Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228(1):273–287.
   PubMed Web of Science ®Google Scholar
• O’Sullivan LA, Liongue C, Lewis RS, et al. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol. 2007;44(10):2497–2506.
   PubMed Web of Science ®Google Scholar
• Schreiner P, Neurath MF, Ng SC, et al. Mechanism-based treatment strategies for IBD: cytokines, cell adhesion molecules, JAK inhibitors, Gut Flora, and More. Inflamm Intest Dis. 2019;4(3):79–96.
   PubMedGoogle Scholar
• Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16:843–862.
   PubMed Web of Science ®Google Scholar
• Pérez-Jeldres T, Tyler CJ, Boyer JD, et al. Targeting cytokine signaling and lymphocyte traffic via small molecules in inflammatory bowel disease: JAK inhibitors and S1PR agonists. Front Pharmacol. 2019;13(10):212.
   Google Scholar
• Hofmann SR, Ettinger R, Zhou YJ, et al. Cytokines and their role in lymphoid development, differentiation and homeostasis. Curr Opin Allergy Clin Immunol. 2002;2(6):495–506.
   PubMed Web of Science ®Google Scholar
• Babon JJ, Lucet IS, Murphy JM, et al. The molecular regulation of Janus kinase (JAK) activation. Biochem J. 2014;462(1):1–13.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Langrish CL, McKenzie BS, Wilson NJ, et al. IL-12 and IL-23: master regulators of innate and adaptive immunity. Immunol Rev. 2004;202(1):96–105.
   PubMedGoogle Scholar
• Agrawal M, Kim ES, Colombel J-F. JAK inhibitors safety in ulcerative colitis: practical implications. J Crohn’s Colitis. 2020:jjaa017. DOI:10.1093/ecco-jcc/jjaa017.
   Google Scholar
• Vavricka SR, Galván JA, Dawson H, et al. Expression patterns of TNFα, MAdCAM1, and STAT3 in intestinal and skin manifestations of inflammatory bowel disease. J Crohns Colitis. 2018;12(3):347–354.
   PubMed Web of Science ®Google Scholar
• Welte T, Zhang SSM, Wang T, et al. STAT3 deletion during hematopoiesis causes Crohn’s disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci U S A. 2003;100(4):1879–1884.
   PubMed Web of Science ®Google Scholar
• Lovato P, Brender C, Agnholt J, et al. Constitutive STAT3 activation in intestinal T cells from patients with Crohn’s disease. J Biol Chem. 2003;278(19):16777–16781.
   PubMed Web of Science ®Google Scholar
• Danese S, Grisham M, Hodge J, et al. JAK inhibition using tofacitinib for inflammatory bowel disease treatment: a hub for multiple inflammatory. Am J Physiol Gastrointest Liver Physiol. 2016;310(3):G155G62.
   Web of Science ®Google Scholar
• Banerjee S, Biehl A, Gadina M, et al. JAK– STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77(5):521–546.
   PubMed Web of Science ®Google Scholar
• Danese S, Allez M, Van Bodegraven AA, et al. Unmet medical needs in ulcerative colitis: an expert group consensus. Dig Dis. 2019;37(4):266–283.
   PubMed Web of Science ®Google Scholar
• D’Amico F, Fiorino G, Furfaro F, et al. Janus kinase inhibitors for the treatment of inflammatory bowel diseases: developments from phase I and phase II clinical trials. Expert Opin Investig Drugs. 2018;27(7):595–599.
   PubMed Web of Science ®Google Scholar
• Hodge JA, Kawabata TT, Krishnaswami S, et al. The mechanism of action of tofacitinib—an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2016;34(2):318–328.
   PubMed Web of Science ®Google Scholar
• Sayoc-Becerra A, Krishnan M, Fan S, et al. The JAK-inhibitor tofacitinib rescues human intestinal epithelial cells and colonoids from cytokine-induced barrier dysfunction. Inflamm Bowel Dis. 2020 March;26(3):407–422.
   PubMed Web of Science ®Google Scholar
• Cordes F, Lenker E, Spille LJ, et al. Tofacitinib reprograms human monocytes of IBD patients and healthy controls toward a more regulatory phenotype. Inflamm Bowel Dis. 2020 Feb 11;26(3):391–406.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Paschos P, Katsoula A, Giouleme O, et al. Tofacitinib for induction of remission in ulcerative colitis: systematic review and meta-analysis. Ann Gastroenterol. 2018;31(5):572–582.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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):123–132.e3.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Panés J, Sandborn WJ, Schreiber S, et al. Tofacitinib for induction and maintenance therapy of Crohn’s disease: results of two phase IIb randomised placebo-controlled trials. Gut. 2017;66:1049–1059.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Ghosh S, Panes J, et al. A Phase 2 study of tofacitinib, an Oral Janus Kinase inhibitor, in patients with crohn’s disease. Clin Gastroenterol Hepatol. 2014;12(9):1485–1493.
   PubMed Web of Science ®Google Scholar
• Sands BE, Panés J, Higgins PDR, et al. 14 Post-hoc analysis of tofacitinib Crohn’s disease phase 2 induction efficacy in subgroups with baseline endoscopic or biomarker evidence of inflammation. Gastroenterology. 2018;154(1):S81.
   Web of Science ®Google Scholar
• Namour F, Diderichsen PM, Cox E, et al. Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 inhibitor, in support of Phase IIB Dose Selection. Clin Pharmacokinet. 2015;54(8):859–874.
   PubMed Web of Science ®Google Scholar
• Namour F, Desrivot J, van der Aa A, et al. Clinical confirmation that the selective JAK 1 inhibitor filgotinib (GLPG0634) has a low liability for drug-drug interactions. Drug Metab Lett. 2016;10:38–48.
   PubMedGoogle Scholar
• Taylor PC, Abdul Azeez M, Kiriakidis S. Filgotinib for the treatment of rheumatoid arthritis. Expert Opin Investig Drugs. 2017;26(10):1181–1187.
   PubMed Web of Science ®Google Scholar
• Namour FV, Vayssiere B, Galien R, et al. AB0494 filgotinib (GLPG0634), a selective JAK1 inhibitor, shows similar PK and PD profiles in Japanese and Caucasian healthy volunteers. Ann Rheum DI. 2015;74(suppl 1):1063–1064.
   Google Scholar
• Vermeire S, Schreiber S, Petryka R, et al. Clinical remission in patients with moderate-to-severe Crohn’s disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet. 2017;389(10066):266–275.
   PubMed Web of Science ®Google Scholar
• Vermeire S, Schreiber S, Petryka R, et al. Maintenance of clinical effect in patients with moderate-to-severe Crohn’s disease treated with filgotinib, a selective JAK1 inhibitor: exploratory 20-week data analysis of the phase 2 fitzroy study. Gastroenterology. 2017;152:S601.
   Web of Science ®Google Scholar
• Mohamed M-EF, Camp HS, Jiang P, et al. Pharmacokinetics, Safety and Tolerability of ABT-494, a novel selective JAK 1 inhibitor, in healthy volunteers and subjects with rheumatoid arthritis. Clin Pharmacokinet. 2016;55(12):1547–1558.
   PubMed Web of Science ®Google Scholar
• Mohamed M-EF, Jungerwirth S, Asatryan A, et al. Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib. Br J Clin Pharmacol. 2017;83(10):2242–2248.
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Ghosh S, Panes J 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. Presentation #OP 195. United Eur Gastroenterol week. 2018.
   Google Scholar
• Panaccione R, Atreya R, Ferrante M, et al. Upadacitinib improves steroid-free clinical and endoscopic endpoints in patients with Crohn’s disease: data from CELEST study. J Crohn’s Colitis. 2018;12(suplement_1):S238–S239.
   Google Scholar
• Panes J, Sanfborn WJ, Loftus EV, et al. Efficacy and safety of upadacitinib maintenance treatment for moderate to severe Crohn’s disease: results from CELEST study. J Crohn’s Colitis. 2018;12(suplement_1):S238–S239.
   Google Scholar
• Schreiber S, Peyrin-Biroulet L, Boland B, et al. Rapidity of clinical and laboratory improvements following upadacitinib induction treatment: data from the CELEST study. J Crohn’s Colitis. 2018;12(Supplement 1):S015.
   Google Scholar
• Beattie D, Tsuruda P, Shen F, et al. TD-1473, a novel, potent, and orally administered, GI-targeted, pan-Janus kinase (JAK) inhibitor. J Crohn’s Colitis. 2016 March 1;10(suppl_1):S123.
   Google Scholar
• Soendergaard C, Bergenheim FH, Bjerrum JT, et al. Targeting JAK-STAT signal transduction in IBD. Pharmacol Ther. 2018;192:100–111.
   PubMed Web of Science ®Google Scholar
• Sandborn W, Bhandari R, Leighton JA, et al. Pan-JAK inhibitor TD-1473 demonstrates favorable safety, tolerability, pharmacokinetics, and signal for clinical activity in subjects with moderately-to-severely active ulcerative colitis. Poster Present Crohn’s Colitis Congr Las Vegas 2019.
   Google Scholar
• Tokarski JS, Zupa-Fernandez A, Tredup JA, et al. Tyrosine kinase 2-mediated signal transduction in T lymphocytes is blocked by pharmacological stabilization of its pseudokinase domain. J Biol Chem. 2015;290:11061–11074.
   PubMed Web of Science ®Google Scholar
• Papp K, Gordon K, Thaçi D, et al. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N Engl J Med. 2018;379:1313–1321.
   PubMed Web of Science ®Google Scholar
• Fensome A, Ambler CM, Arnold E, et al. Dual inhibition of TYK2 and JAK1 for the treatment of autoimmune diseases: discovery of ((S)-2,2-difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1] octan-8-yl)methanone (PF-06700841). J Med Chem. 2018;61:8597–8612.
   PubMed Web of Science ®Google Scholar
• Telliez JB, Dowty ME, Wang L, et al. Discovery of a JAK3-selective inhibitor: functional differentiation of JAK3-selective inhibition over pan-JAK or JAK1-selective inhibition. ACS Chem Biol. 2016;11:3442–3451.
   PubMed Web of Science ®Google Scholar
• Thorarensen A, Dowty ME, Banker ME, et al. Design of a Janus kinase 3 (JAK3) specific inhibitor 1-((2S,5R)-5-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) allowing for the interrogation of JAK3 signaling in humans. J Med Chem. 2017;60:1971–1993.
   PubMed Web of Science ®Google Scholar
• Fiorino G, D’Amico F, Italia A, et al. JAK inhibitors: novel developments in management of ulcerative colitis. Best Pract Res Clin Gastroenterol. 2018;3233:89–93.
   Google Scholar
• Bonovas S, Lytras T, Nikolopoulos, et al. Editorial: tofacitinib and biologics for moderate-to-severe ulcerative colitis-what is best in class? Authors’ reply. Aliment Pharmacol Ther. 2018;47:540–541.
   PubMed Web of Science ®Google Scholar
• Bonovas S, Lytras T, Nikolopoulos, et al., Systematic review with network meta-analysis: comparative assessment of tofacitinib and biological therapies for moderate-to-severe ulcerative colitis. Aliment Pharmacol Ther. 2018;47(4):454–465.
   PubMed Web of Science ®Google Scholar
• Verden A, Dimbil M, Kyle R, et al. Analysis of spontaneous postmarket case reports submitted to the FDA regarding thromboembolic adverse events and JAK inhibitors. Drug Saf. 2018;41(4):357–361.
   PubMed Web of Science ®Google Scholar
• Cremer A, Lobaton T, Vieujan S, et al. P422 Tofacitinib induces clinical and endoscopic remission in biologic refractory ulcerative colitis patients: a real-world Belgian cohort study. J Crohn’s Colitis. 2020;14(Supplement_1):S384–S386.
   Google Scholar
• 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;158(6):1554–1573.e12. S0016-5085(20)30011-1.
   PubMed Web of Science ®Google Scholar
• Verstockt B, Verstockt S, Alsaoud D, et al. P385 A mucosal marker predicting tofacitinib induced an endoscopic response in ulcerative colitis. J Crohn’s Colitis. 2020;14(Supplement_1):S358–S359.
   Google Scholar