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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Review Article

JAK Inhibition as a Therapeutic Strategy for Inflammatory Bowel Disease

Author(s): Fabio Salvatore Macaluso* and Iago Rodríguez-Lago

Volume 21, Issue 4, 2020

Page: [247 - 255] Pages: 9

DOI: 10.2174/1389200221666200310111409

Price: $65

Abstract

Background: Inflammatory bowel disease, including both Crohn’s disease and ulcerative colitis, are two chronic and progressive disorders affecting the gastrointestinal tract. Research on the molecular mechanisms of both diseases has led to the introduction of targeted therapies which are able to selectively block the key inflammatory mediators.

Methods: Here, we discuss the current evidence about the mechanism of action with an up to date review of the efficacy and safety of Janus kinase inhibitors in inflammatory bowel disease.

Results: Multiple small molecule drugs have been evaluated for their use in both ulcerative colitis and Crohn’s disease. Janus kinase inhibitors represent the most important family of these drugs, as their particular mechanism of action enables a simultaneous and effective blockade of multiple cytokines involved in the pathogenesis of the disease.

Conclusion: Janus kinase inhibitors represent a promising therapeutic strategy, especially in ulcerative colitis. More data are still necessary regarding its efficacy and safety in clinical practice.

Keywords: Crohn's disease, JAK, ulcerative colitis, inflammatory bowel disease, targeted therapies, molecular mechanisms.

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[1]
Abraham, C.; Cho, J.H. Inflammatory bowel disease. N. Engl. J. Med., 2009, 361(21), 2066-2078.
[http://dx.doi.org/10.1056/NEJMra0804647] [PMID: 19923578]
[2]
Hazlewood, GS; Rezaie, A; Borman, M; Panaccione, R; Ghosh, S; Seow, CH Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis. Gastroenterology.,, 2015,, 148( (2),344.54 e5; quiz e14-5)
[http://dx.doi.org/10.1053/j.gastro.2014.10.011]
[3]
Lv, R.; Qiao, W.; Wu, Z.; Wang, Y.; Dai, S.; Liu, Q.; Zheng, X. Tumor necrosis factor alpha blocking agents as treatment for ulcerative colitis intolerant or refractory to conventional medical therapy: a meta-analysis. PLoS One, 2014, 9(1)e86692
[http://dx.doi.org/10.1371/journal.pone.0086692] [PMID: 24475168]
[4]
Armuzzi, A.; Gionchetti, P.; Daperno, M.; Danese, S.; Orlando, A.; Lia Scribano, M.; Vecchi, M.; Rizzello, F. GIVI (Gruppo Italiano su Vedolizumab nelle IBD) Group. Expert consensus paper on the use of Vedolizumab for the management of patients with moderate-to-severe Inflammatory Bowel Disease. Dig. Liver Dis., 2016, 48(4), 360-370.
[http://dx.doi.org/10.1016/j.dld.2015.12.016] [PMID: 26821929]
[5]
Macaluso, F.S.; Orlando, A.; Cottone, M. Anti-interleukin-12 and anti-interleukin-23 agents in Crohn’s disease. Expert Opin. Biol. Ther., 2019, 19(2), 89-98.
[http://dx.doi.org/10.1080/14712598.2019.1561850] [PMID: 30571147]
[6]
Ben-Horin, S.; Chowers, Y. loss of response to anti-TNF treatments in Crohn’s disease. Aliment. Pharmacol. Ther., 2011, 33(9), 987-995.
[http://dx.doi.org/10.1111/j.1365-2036.2011.04612.x] [PMID: 21366636]
[7]
Sands, BE; Feagan, BG; Rutgeerts, P.; Colombel, JF; Sandborn, WJ Sy, R Effects of vedolizumab induction therapy for patients with Crohn’s disease in whom tumor necrosis factor antagonist treatment failed. Gastroenterology, 2014, 147(3), 618-27.e3.
[http://dx.doi.org/10.1053/j.gastro.2014.05.008]
[8]
Feagan, B.G.; Sandborn, W.J.; Gasink, C.; Jacobstein, D.; Lang, Y.; Friedman, J.R.; Blank, M.A.; Johanns, J.; Gao, L.L.; Miao, Y.; Adedokun, O.J.; Sands, B.E.; Hanauer, S.B.; Vermeire, S.; Targan, S.; Ghosh, S.; de Villiers, W.J.; Colombel, J.F.; Tulassay, Z.; Seidler, U.; Salzberg, B.A.; Desreumaux, P.; Lee, S.D.; Loftus, E.V., Jr; Dieleman, L.A.; Katz, S.; Rutgeerts, P. UNITI–IM-UNITI Study Group. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N. Engl. J. Med., 2016, 375(20), 1946-1960.
[http://dx.doi.org/10.1056/NEJMoa1602773] [PMID: 27959607]
[9]
Murphy, A.G.; Zheng, L. Small molecule drugs with immunomodulatory effects in cancer. Hum. Vaccin. Immunother., 2015, 11(10), 2463-2468.
[http://dx.doi.org/10.1080/21645515.2015.1057363] [PMID: 26110550]
[10]
Pérez-Jeldres, T.; Tyler, C.J.; Boyer, J.D.; Karuppuchamy, T.; Yarur, A.; Giles, D.A.; Yeasmin, S.; Lundborg, L.; Sandborn, W.J.; Patel, D.R.; Rivera-Nieves, J. Targeting cytokine signaling and lymphocyte traffic via small molecules in inflammatory bowel disease: JAK inhibitors and S1PR agonists. Front. Pharmacol., 2019, 10, 212.
[http://dx.doi.org/10.3389/fphar.2019.00212] [PMID: 30930775]
[11]
Olivera, P.; Danese, S.; Peyrin-Biroulet, L. JAK inhibition in inflammatory bowel disease. Expert Rev. Clin. Immunol., 2017, 13(7), 693-703.
[http://dx.doi.org/10.1080/1744666X.2017.1291342] [PMID: 28164724]
[12]
D’Amico, F.; Parigi, T.L.; Fiorino, G.; Peyrin-Biroulet, L.; Danese, S. Tofacitinib in the treatment of ulcerative colitis: efficacy and safety from clinical trials to real-world experience. Therap. Adv. Gastroenterol., 2019, 121756284819848631
[http://dx.doi.org/10.1177/1756284819848631] [PMID: 31205486]
[13]
O’Shea, J.J.; Holland, S.M.; Staudt, L.M. JAKs and STATs in immunity, immunodeficiency, and cancer. N. Engl. J. Med., 2013, 368(2), 161-170.
[http://dx.doi.org/10.1056/NEJMra1202117] [PMID: 23301733]
[14]
Leonard, W.J.; O’Shea, J.J. Jaks and STATs: biological implications. Annu. Rev. Immunol., 1998, 16, 293-322.
[http://dx.doi.org/10.1146/annurev.immunol.16.1.293] [PMID: 9597132]
[15]
Mavers, M.; Ruderman, E.M.; Perlman, H. Intracellular signal pathways: potential for therapies. Curr. Rheumatol. Rep., 2009, 11(5), 378-385.
[http://dx.doi.org/10.1007/s11926-009-0054-9] [PMID: 19772834]
[16]
Ghoreschi, K.; Laurence, A.; O’Shea, J.J. Janus kinases in immune cell signaling. Immunol. Rev., 2009, 228(1), 273-287.
[http://dx.doi.org/10.1111/j.1600-065X.2008.00754.x] [PMID: 19290934]
[17]
Fernández-Clotet, A.; Castro-Poceiro, J.; Panés, J. Tofacitinib for the treatment of ulcerative colitis. Expert Rev. Clin. Immunol., 2018, 14(11), 881-892.
[http://dx.doi.org/10.1080/1744666X.2018.1532291] [PMID: 30285500]
[18]
Leonard, W.J.; Lin, J.X.; O’Shea, J.J. The γc family of cytokines: basic biology to therapeutic ramifications. Immunity, 2019, 50(4), 832-850.
[http://dx.doi.org/10.1016/j.immuni.2019.03.028] [PMID: 30995502]
[19]
Hofmann, S.R.; Ettinger, R.; Zhou, Y.J.; Gadina, M.; Lipsky, P.; Siegel, R.; Candotti, F.; O’Shea, J.J. Cytokines and their role in lymphoid development, differentiation and homeostasis. Curr. Opin. Allergy Clin. Immunol., 2002, 2(6), 495-506.
[http://dx.doi.org/10.1097/00130832-200212000-00004] [PMID: 14752332]
[20]
de Groot, R.P.; Coffer, P.J.; Koenderman, L. Regulation of proliferation, differentiation and survival by the IL-3/IL-5/GM-CSF receptor family. Cell. Signal., 1998, 10(9), 619-628.
[http://dx.doi.org/10.1016/S0898-6568(98)00023-0] [PMID: 9794243]
[21]
O’Sullivan, L.A.; Liongue, C.; Lewis, R.S.; Stephenson, S.E.; Ward, A.C. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol. Immunol., 2007, 44(10), 2497-2506.
[http://dx.doi.org/10.1016/j.molimm.2006.11.025] [PMID: 17208301]
[22]
Jones, S.A.; Jenkins, B.J. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat. Rev. Immunol., 2018, 18(12), 773-789.
[http://dx.doi.org/10.1038/s41577-018-0066-7] [PMID: 30254251]
[23]
Jamilloux, Y.; El Jammal, T.; Vuitton, L.; Gerfaud-Valentin, M.; Kerever, S.; Sève, P. JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun. Rev., 2019, 18(11)102390
[http://dx.doi.org/10.1016/j.autrev.2019.102390] [PMID: 31520803]
[24]
Phan, K.; Sebaratnam, D.F. JAK inhibitors for alopecia areata: a systematic review and meta-analysis. J. Eur. Acad. Dermatol. Venereol., 2019, 33(5), 850-856.
[http://dx.doi.org/10.1111/jdv.15489] [PMID: 30762909]
[25]
Barbulescu, C.C.; Goldstein, N.B.; Roop, D.R.; Norris, D.A.; Birlea, S.A. Harnessing the power of regenerative therapy for vitiligo and alopecia areata. J. Invest. Dermatol., 2020, 140(1), 29-37.
[http://dx.doi.org/10.1016/j.jid.2019.03.1142] [PMID: 31196751]
[26]
Peyrin-Biroulet, L.; Demarest, S.; Nirula, A. Bispecific antibodies: the next generation of targeted inflammatory bowel disease therapies. Autoimmun. Rev., 2019, 18(2), 123-128.
[http://dx.doi.org/10.1016/j.autrev.2018.07.014] [PMID: 30572136]
[27]
Clark, J.D.; Flanagan, M.E.; Telliez, J.B. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J. Med. Chem., 2014, 57(12), 5023-5038.
[http://dx.doi.org/10.1021/jm401490p] [PMID: 24417533]
[28]
Sandborn, W.J.; Su, C.; Sands, B.E.; D’Haens, G.R.; Vermeire, S.; Schreiber, S.; Danese, S.; Feagan, B.G.; Reinisch, W.; Niezychowski, W.; Friedman, G.; Lawendy, N.; Yu, D.; Woodworth, D.; Mukherjee, A.; Zhang, H.; Healey, P.; Panés, J. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med., 2017, 376(18), 1723-1736.
[http://dx.doi.org/10.1056/NEJMoa1606910] [PMID: 28467869]
[29]
Sandborn, W.J.; Ghosh, S.; Panes, J.; Vranic, I.; Su, C.; Rousell, S.; Niezychowski, W. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N. Engl. J. Med., 2012, 367(7), 616-624.
[http://dx.doi.org/10.1056/NEJMoa1112168] [PMID: 22894574]
[30]
Macaluso, F.S.; Maida, M.; Ventimiglia, M.; Renna, S.; Cottone, M.; Orlando, A. Factors affecting clinical and endoscopic outcomes of placebo arm in trials of biologics and small molecule drugs in ulcerative colitis: a meta-analysis. Inflamm. Bowel Dis., 2019, 25(6), 987-997.
[http://dx.doi.org/10.1093/ibd/izy365] [PMID: 30590590]
[31]
Hanauer, S.; Panaccione, R.; Danese, S.; Cheifetz, A.; Reinisch, W.; Higgins, P.D.R.; Woodworth, D.A.; Zhang, H.; Friedman, G.S.; Lawendy, N.; Quirk, D.; Nduaka, C.I.; Su, C. Tofacitinib induction therapy reduces symptoms within 3 days for patients with ulcerative colitis. Clin. Gastroenterol. Hepatol., 2019, 17(1), 139-147.
[http://dx.doi.org/10.1016/j.cgh.2018.07.009] [PMID: 30012431]
[32]
Sands, B.E.; Armuzzi, A.; Marshall, J.K.; Lindsay, J.O.; Sandborn, W.J.; Danese, S. Efficacy and safety of tofacitinib dose de-escalation and dose escalation for patients with ulcerative colitis: results from OCTAVE Open. Aliment. Pharmacol. Ther., 2019..
[PMID: 31660640]
[33]
Panés, J.; Sandborn, W.J.; Schreiber, S.; Sands, B.E.; Vermeire, S.; D’Haens, G.; Panaccione, R.; Higgins, P.D.R.; Colombel, J.F.; Feagan, B.G.; Chan, G.; Moscariello, M.; Wang, W.; Niezychowski, W.; Marren, A.; Healey, P.; Maller, E. Tofacitinib for induction and maintenance therapy of Crohn’s disease: results of two phase IIb randomised placebo-controlled trials. Gut, 2017, 66(6), 1049-1059.
[http://dx.doi.org/10.1136/gutjnl-2016-312735] [PMID: 28209624]
[34]
Sandborn, WJ; Ghosh, S.; Panes, J.; Vranic, I.; Wang, W.; Niezychowski, W. A phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn’s disease. Clin. Gastroenterol. Hepatol., 2014, 12(9), 1485-93.e2.
[http://dx.doi.org/10.1016/j.cgh.2014.01.029]
[35]
Panés, J.; D’Haens, G.R.; Higgins, P.D.R.; Mele, L.; Moscariello, M.; Chan, G.; Wang, W.; Niezychowski, W.; Su, C.; Maller, E. Long-term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open-label, 48-week extension study. Aliment. Pharmacol. Ther., 2019, 49(3), 265-276.
[http://dx.doi.org/10.1111/apt.15072] [PMID: 30663107]
[36]
Vermeire, S.; Schreiber, S.; Petryka, R.; Kuehbacher, T.; Hebuterne, X.; Roblin, X.; Klopocka, M.; Goldis, A.; Wisniewska-Jarosinska, M.; Baranovsky, A.; Sike, R.; Stoyanova, K.; Tasset, C.; Van der Aa, A.; Harrison, P. 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.
[http://dx.doi.org/10.1016/S0140-6736(16)32537-5] [PMID: 27988142]
[37]
Sandborn, W.J.; Feagan, B.G.; Panes, J.; D’Haens, G.R.; Colombel, J.F.; Zhou, Q. Safety and efficacy of ABT-494 (Upadacitinib), an oral jak1 inhibitor, as induction therapy in patients with crohn’s disease: results from celest. Gastroenterology, 2017, 152(5), S1308-S9.
[http://dx.doi.org/10.1016/S0016-5085(17)34357-3]
[38]
Panes, J; Sandborn, WJ; Loftus, EV, Jr; Van Assche, G; Ghosh, S; Zhou, Q P273 efficacy and safety of upadacitinib maintenance treatment for moderate to severe crohn’s disease: results from the CELEST study. J. Crohn's Colitis,, 2018,, 12(supplement_1),, S238-- S9.
[39]
Sandborn, W.J.; Bhandari, R.; Leighton, J.; Ganeshappa, R.; Nguyen, D.; Ferslew, B. P041 The gut-selective, orally administered, pan-jak inhibitor td-1473 demonstrates favorable safety, tolerability, pharmacokinetic, and signal for clinical activity in subjects with moderately-to-severely active ulcerative colitis. Gastroenterology, 2019, 156(3), S29-S30.
[http://dx.doi.org/10.1053/j.gastro.2019.01.093]
[40]
Papp, K.; Gordon, K.; Thaçi, D.; Morita, A.; Gooderham, M.; Foley, P.; Girgis, I.G.; Kundu, S.; Banerjee, S. Phase 2 trial of selective tyrosine kinase 2 inhibition in psoriasis. N. Engl. J. Med., 2018, 379(14), 1313-1321.
[http://dx.doi.org/10.1056/NEJMoa1806382] [PMID: 30205746]
[41]
Papp, K.; Pariser, D.; Catlin, M.; Wierz, G.; Ball, G.; Akinlade, B.; Zeiher, B.; Krueger, J.G. A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis. Br. J. Dermatol., 2015, 173(3), 767-776.
[http://dx.doi.org/10.1111/bjd.13745] [PMID: 25704750]
[42]
Takeuchi, T.; Tanaka, Y.; Iwasaki, M.; Ishikura, H.; Saeki, S.; Kaneko, Y. Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study. Ann. Rheum. Dis., 2016, 75(6), 1057-1064.
[http://dx.doi.org/10.1136/annrheumdis-2015-208279] [PMID: 26672064]
[43]
Genovese, M.C.; Greenwald, M.; Codding, C.; Zubrzycka-Sienkiewicz, A.; Kivitz, A.J.; Wang, A.; Shay, K.; Wang, X.; Garg, J.P.; Cardiel, M.H. Peficitinib, a JAK Inhibitor, in combination with limited conventional synthetic disease-modifying antirheumatic drugs in the treatment of moderate-to-severe rheumatoid arthritis. Arthritis Rheumatol., 2017, 69(5), 932-942.
[http://dx.doi.org/10.1002/art.40054] [PMID: 28118538]
[44]
Sands, B.E.; Sandborn, W.J.; Feagan, B.G.; Lichtenstein, G.R.; Zhang, H.; Strauss, R.; Szapary, P.; Johanns, J.; Panes, J.; Vermeire, S.; O’Brien, C.D.; Yang, Z.; Bertelsen, K.; Marano, C. Peficitinib, an oral janus kinase inhibitor, in moderate-to-severe ulcerative colitis: results from a randomised, phase 2 study. J. Crohn’s Colitis, 2018, 12(10), 1158-1169.
[http://dx.doi.org/10.1093/ecco-jcc/jjy085] [PMID: 29917064]
[45]
Beaugerie, L.; Kirchgesner, J. Balancing benefit vs risk of immunosuppressive therapy for individual patients with inflammatory bowel diseases. Clin. Gastroenterol. Hepatol., 2019, 17(3), 370-379.
[http://dx.doi.org/10.1016/j.cgh.2018.07.013] [PMID: 30031174]
[46]
Zabana, Y.; Rodríguez, L.; Lobatón, T.; Gordillo, J.; Montserrat, A.; Mena, R.; Beltrán, B.; Dotti, M.; Benitez, O.; Guardiola, J.; Domènech, E.; Garcia-Planella, E.; Calvet, X.; Piqueras, M.; Aceituno, M.; Fernández-Bañares, F.; Esteve, M. Relevant infections in inflammatory bowel disease, and their relationship with immunosuppressive therapy and their effects on disease mortality. J. Crohn’s Colitis, 2019, 13(7), 828-837.
[http://dx.doi.org/10.1093/ecco-jcc/jjz013] [PMID: 30668662]
[47]
Kirchgesner, J.; Lemaitre, M.; Carrat, F.; Zureik, M.; Carbonnel, F.; Dray-Spira, R. Risk of serious and opportunistic infections associated with treatment of inflammatory bowel diseases. J Crohns Colitis.,, 2018,, 13( (7),), 828-- 37.
[http://dx.doi.org/10.1053/j.gastro.2018.04.012]
[48]
Sandborn, W.J.; Panés, J.; D’Haens, G.R.; Sands, B.E.; Su, C.; Moscariello, M.; Jones, T.; Pedersen, R.; Friedman, G.S.; Lawendy, N.; Chan, G. Safety of tofacitinib for treatment of ulcerative colitis, based on 4.4 years of data from global clinical trials. Clin. Gastroenterol. Hepatol., 2019, 17(8), 1541-1550.
[http://dx.doi.org/10.1016/j.cgh.2018.11.035] [PMID: 30476584]
[49]
Colombel, J.F. Herpes zoster in patients receiving jak inhibitors for ulcerative colitis: mechanism, epidemiology, management, and prevention. Inflamm. Bowel Dis., 2018, 24(10), 2173-2182.
[http://dx.doi.org/10.1093/ibd/izy150] [PMID: 29788127]
[50]
Winthrop, K.L.; Yamanaka, H.; Valdez, H.; Mortensen, E.; Chew, R.; Krishnaswami, S.; Kawabata, T.; Riese, R. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol., 2014, 66(10), 2675-2684.
[http://dx.doi.org/10.1002/art.38745] [PMID: 24943354]
[51]
Winthrop, K.L.; Melmed, G.Y.; Vermeire, S.; Long, M.D.; Chan, G.; Pedersen, R.D.; Lawendy, N.; Thorpe, A.J.; Nduaka, C.I.; Su, C. Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib. Inflamm. Bowel Dis., 2018, 24(10), 2258-2265.
[http://dx.doi.org/10.1093/ibd/izy131] [PMID: 29850873]
[52]
Sands, BE.; Taub, PR.; Armuzzi, A.; Friedman, GS.; Moscariello, M.; Lawendy, N. 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.
[http://dx.doi.org/10.1016/j.cgh.2019.04.059]
[53]
Wollenhaupt, J.; Lee, E.B.; Curtis, J.R.; Silverfield, J.; Terry, K.; Soma, K.; Mojcik, C.; DeMasi, R.; Strengholt, S.; Kwok, K.; Lazariciu, I.; Wang, L.; Cohen, S. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res. Ther., 2019, 21(1), 89.
[http://dx.doi.org/10.1186/s13075-019-1866-2] [PMID: 30953540]
[54]
Aarestrup, J.; Jess, T.; Kobylecki, C.J.; Nordestgaard, B.G.; Allin, K.H. Cardiovascular risk profile among patients with inflammatory bowel disease: a population-based study of more than 100 000 individuals. J. Crohn’s Colitis, 2019, 13(3), 319-323.
[http://dx.doi.org/10.1093/ecco-jcc/jjy164] [PMID: 30321330]
[55]
Purnak, T.; Yuksel, O. Overview of venous thrombosis in inflammatory bowel disease. Inflamm. Bowel Dis., 2015, 21(5), 1195-1203.
[http://dx.doi.org/10.1097/MIB.0000000000000274] [PMID: 25581828]
[56]
Sandborn, W.J.; Panés, J.; Sands, B.E.; Reinisch, W.; Su, C.; Lawendy, N.; Koram, N.; Fan, H.; Jones, T.V.; Modesto, I.; Quirk, D.; Danese, S. Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme. Aliment. Pharmacol. Ther., 2019, 50(10), 1068-1076.
[http://dx.doi.org/10.1111/apt.15514] [PMID: 31599001]
[57]
Available from. https://www.accessdata.fda.gov/drugsatfda_docs/ label/2018/203214s018lbl.pdf
[58]
Xie, F.; Yun, H.; Bernatsky, S.; Curtis, J.R. Brief Report: Risk of Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologic Treatments. Arthritis Rheumatol., 2016, 68(11), 2612-2617.
[http://dx.doi.org/10.1002/art.39761] [PMID: 27213279]
[59]
Mahadevan, U.; Robinson, C.; Bernasko, N.; Boland, B.; Chambers, C.; Dubinsky, M.; Friedman, S.; Kane, S.; Manthey, J.; Sauberan, J.; Stone, J.; Jain, R. Inflammatory bowel disease in pregnancy clinical care pathway: a report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology, 2019, 156(5), 1508-1524.
[http://dx.doi.org/10.1053/j.gastro.2018.12.022] [PMID: 30658060]
[60]
Mahadevan, U.; Dubinsky, M.C.; Su, C.; Lawendy, N.; Jones, T.V.; Marren, A.; Zhang, H.; Graham, D.; Clowse, M.E.B.; Feldman, S.R.; Baumgart, D.C. Outcomes of Pregnancies With Maternal/Paternal Exposure in the Tofacitinib Safety Databases for Ulcerative Colitis. Inflamm. Bowel Dis., 2018, 24(12), 2494-2500.
[http://dx.doi.org/10.1093/ibd/izy160] [PMID: 29982686]
[61]
Clowse, M.E.; Feldman, S.R.; Isaacs, J.D.; Kimball, A.B.; Strand, V.; Warren, R.B.; Xibillé, D.; Chen, Y.; Frazier, D.; Geier, J.; Proulx, J.; Marren, A. Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis. Drug Saf., 2016, 39(8), 755-762.
[http://dx.doi.org/10.1007/s40264-016-0431-z] [PMID: 27282428]
[62]
Mazzola, G.; Macaluso, F.S.; Adamoli, L.; Renna, S.; Cascio, A.; Orlando, A. Diagnostic and vaccine strategies to prevent infections in patients with inflammatory bowel disease. J. Infect., 2017, 74(5), 433-441.
[http://dx.doi.org/10.1016/j.jinf.2017.02.009] [PMID: 28263759]

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