Update on Janus Kinase Antagonists in Inflammatory Bowel Disease

Gastroenterology Clinics of North America

Volumn 43, Issue 3, 2014, Pages 603-617

  Boland, Brigid S ^a,b   Sandborn, William J ^a,b   Chang, John T ^a,b  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Crohn disease; Inflammatory bowel disease; Janus kinase inhibitors; Small molecule therapy; Tofacitinib; Ulcerative colitis

Indexed keywords

ADALIMUMAB; BARICITINIB; CERTOLIZUMAB PEGOL; CYTOKINE RECEPTOR; CYTOKINE RECEPTOR 1; CYTOKINE RECEPTOR 2; DECERNOTINIB; DISEASE MODIFYING ANTIRHEUMATIC DRUG; GLPG 0634; GLPG 0974; HIGH DENSITY LIPOPROTEIN; JANUS KINASE 1; JANUS KINASE 2; JANUS KINASE 3; JANUS KINASE INHIBITOR; JNJ 54781532; LOW DENSITY LIPOPROTEIN CHOLESTEROL; METHOTREXATE; PEFICITINIB; PLACEBO; RUXOLITINIB; STAT PROTEIN; TOFACITINIB; UNCLASSIFIED DRUG; JANUS KINASE; PIPERIDINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE;

ABDOMINAL PAIN; AUTOIMMUNE DISEASE; BONE MARROW SUPPRESSION; BRONCHIECTASIS; BRONCHITIS; CANCER RISK; CARDIOVASCULAR DISEASE; CELLULITIS; CHOLESTEROL BLOOD LEVEL; COLITIS; CONGESTIVE HEART FAILURE; CROHN DISEASE; DIABETIC FOOT; DISEASE EXACERBATION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FATALITY; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSLIPIDEMIA; ENZYME ANALYSIS; ENZYME DEFICIENCY; ENZYME INHIBITION; GENETIC ASSOCIATION; GRAFT REJECTION; HERPES ZOSTER; HUMAN; INFECTION; INFECTION RISK; INFLAMMATORY BOWEL DISEASE; INFLUENZA; LIPOPROTEIN BLOOD LEVEL; LIVER ABSCESS; LIVER TOXICITY; LUNG TUBERCULOSIS; LYMPHOMA; MALIGNANT NEOPLASTIC DISEASE; MULTICENTER STUDY (TOPIC); MYELOFIBROSIS; NAUSEA; NEPHROTOXICITY; NEUTROPENIA; NEUTROPHIL COUNT; NONHUMAN; OPPORTUNISTIC INFECTION; OUTCOME ASSESSMENT; PERIANAL ABSCESS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; PROTEIN EXPRESSION; PROTEIN FAMILY; PSORIASIS; PULMONARY CRYPTOCOCCOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RHEUMATOID ARTHRITIS; RHINOPHARYNGITIS; SEPSIS; SIDE EFFECT; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SOLID TUMOR; TREATMENT DURATION; TUBERCULOUS PLEURISY; ULCERATIVE COLITIS; VOMITING; VULVA ABSCESS; VULVA DISEASE; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; DEFICIENCY; DRUG EFFECTS; INFLAMMATORY BOWEL DISEASES;

ANIMALS; DYSLIPIDEMIAS; HUMANS; INFLAMMATORY BOWEL DISEASES; JANUS KINASES; OPPORTUNISTIC INFECTIONS; PIPERIDINES; PROTEIN KINASE INHIBITORS; PYRIMIDINES; PYRROLES; SIGNAL TRANSDUCTION;

EID: 84905724744     PISSN: 08898553     EISSN: 15581942     Source Type: Journal    
DOI: 10.1016/j.gtc.2014.05.011     Document Type: Review

References (51)

1. Abraham C., Cho J.H. Inflammatory bowel disease. N Engl J Med 2009, 361:2066-2078.
2. Baumgart D.C., Sandborn W.J. Crohn's disease. Lancet 2012, 380:1590-1605.
3. Xavier R.J., Podolsky D.K. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007, 448:427-434.
4. Kontzias A., Kotlyar A., Laurence A., et al. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol 2012, 12:464-470.
5. Flanagan M.E., Blumenkopf T.A., Brissette W.H., 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, 53:8468-8484.
6. Harpur A.G., Andres A.C., Ziemiecki A., et al. JAK2, a third member of the JAK family of protein tyrosine kinases. Oncogene 1992, 7:1347-1353.
7. Saharinen P., Silvennoinen O. The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. J Biol Chem 2002, 277:47954-47963.
8. Ghoreschi K., Laurence A., O'Shea J.J. Janus kinases in immune cell signaling. Immunol Rev 2009, 228:273-287.
9. Darnell J.E. STATs and gene regulation. Science 1997, 277:1630-1635.
10. Darnell J.E., Kerr I.M., Stark G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994, 264:1415-1421.
11. Gadina M., Hilton D., Johnston J.A., et al. Signaling by type I and II cytokine receptors: ten years after. Curr Opin Immunol 2001, 13:363-373.
12. Dumoutier L., Lejeune D., Hor S., et al. Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3. Biochem J 2003, 370:391-396.
13. O'Shea J.J., Kontzias A., Yamaoka K., et al. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis 2013, 72(Suppl 2):ii111-ii115.
14. Shuai K., Liu B. Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 2003, 3:900-911.
15. Casanova J.L., Holland S.M., Notarangelo L.D. Inborn errors of human JAKs and STATs. Immunity 2012, 36:515-528.
16. Kilic S.S., Hacimustafaoglu M., Boisson-Dupuis S., et al. A patient with tyrosine kinase 2 deficiency without hyper-IgE syndrome. J Pediatr 2012, 160:1055-1057.
17. O'Shea J.J., Holland S.M., Staudt L.M. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med 2013, 368:161-170.
18. White H., Thrasher A., Veys P., et al. Intrinsic defects of B cell function in X-linked severe combined immunodeficiency. Eur J Immunol 2000, 30:732-737.
19. Buckley R.H. B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review. J Allergy Clin Immunol 2010, 125:790-797.
20. Ghoreschi K., Jesson M.I., Li X., et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol 2011, 186:4234-4243.
21. Shi M., Lin T.H., Appell K.C., et al. Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation. Immunity 2008, 28:763-773.
22. Cho J.H., Gregersen P.K. Genomics and the multifactorial nature of human autoimmune disease. N Engl J Med 2011, 365:1612-1623.
23. Jostins L., Ripke S., Weersma R.K., et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012, 491:119-124.
24. Danese S., Fiocchi C. Ulcerative colitis. N Engl J Med 2011, 365:1713-1725.
25. Karaman M.W., Herrgard S., Treiber D.K., et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008, 26:127-132.
26. Meyer D.M., Jesson M.I., Li X., et al. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J Inflamm (Lond) 2010, 7:41.
27. Changelian P.S., Flanagan M.E., Ball D.J., et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 2003, 302:875-878.
28. Fleischmann R., Kremer J., Cush J., et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 2012, 367:495-507.
29. Kremer J., Li Z.G., Hall S., et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med 2013, 159:253-261.
30. van Vollenhoven R.F., Fleischmann R., Cohen S., et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012, 367:508-519.
31. Sandborn W.J., Ghosh S., Panes J., et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med 2012, 367:616-624.
32. Sandborn W.J., 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, [Epub ahead of print].
33. Targan S.R., Hanauer S.B., van Deventer S.J., et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med 1997, 337:1029-1035.
34. Hanauer S.B., Sandborn W.J., Rutgeerts P., et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology 2006, 130:323-333. [quiz: 591].
35. Modigliani R., Mary J.Y., Simon J.F., et al. Clinical, biological, and endoscopic picture of attacks of Crohn's disease. Evolution on prednisolone. Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives. Gastroenterology 1990, 98:811-818.
36. Lahiff C., Safaie P., Awais A., et al. The Crohn's disease activity index (CDAI) is similarly elevated in patients with Crohn's disease and in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2013, 37:786-794.
37. Cellier C., Sahmoud T., Froguel E., et al. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Gut 1994, 35:231-235.
38. Sandborn W.J., Schreiber S., Feagan B.G., et al. Certolizumab pegol for active Crohn's disease: a placebo-controlled, randomized trial. Clin Gastroenterol Hepatol 2011, 9:670-678.e3.
39. Kawalec P., Mikrut A., Wisniewska N., et al. The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol 2013, 32:1415-1424.
40. Pfizer. Advisory Committee Meeting: Tofacitinib for treatment of rheumatoid arthritis (NDA 203214). May 9, 2012 edition. Available at. Accessed February 14, 2014. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM302960/.
41. McInnes I.B., Kim H.Y., Lee S.H., et al. Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study. Ann Rheum Dis 2014, 73:124-131.
42. Maini R.N., Taylor P.C., Szechinski J., et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum 2006, 54:2817-2829.
43. Verstovsek S., Kantarjian H., Mesa R.A., et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010, 363:1117-1127.
44. Verstovsek S., Kantarjian H.M., Estrov Z., et al. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood 2012, 120:1202-1209.
45. Williams W., Scherle P., Shi J., et al. A randomized placebo-controlled study of INCB018424, a selective Janus kinase 1 & 2 (JAK 1&2) inhibitor in rheumatoid arthritis (RA). Arthritis Rheum 2008, 58:S431.
46. Keystone E., Taylor P., Genovese M., et al. 12-Week results of a Phase 2B dose-ranging study of LY3009104 (INCB028050), an oral JAJ/JAK2 inhibitor, in combination with traditional DMARDs in patients with rheumatoid arthritis. Ann Rheum Dis 2012, 71:S3.
47. Janssen Research & Development, LLC. A study of safety and effectiveness of JNJ-54781532 in patients with moderately to severely active ulcerative colitis. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (USA); 2000-2014. Available at. http://clinicaltrials.gov/ct2/show/NCT01959282.
48. Vanhoutte F.P., Mazur M., Namour F., et al. Efficacy and safety of GLPG0634, a selective JAK1 inhibitor, after short-term treatment of rheumatoid arthritis: results of a phase IIa trial. Ann Rheum Dis 2012, 71:S3.
49. Merciris D, Delachaume C, De Vriendt V, et al. GLPG0634, the first selective JAK1 inhibitor, shows strong activity in the mouse DSS-colitis model. Congress of ECCO. Denmark, February 21, 2014.
50. Fleischmann R., Spencer-Green G.T., Fan F., et al. Dose ranging study of VX-509, an oral selective JAK3 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA). Arthritis Rheum 2011, 63:LB3.
51. Vanhoutte F, Namour F, Dupont S, et al. The FFA2 antagonist GLPG0974: opportunity to treat neutrophil-driven inflammation. Congress of ECCO. 2014.