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.
[http://dx.doi.org/10.1056/NEJMra0804647] [PMID: 19923578]
[http://dx.doi.org/10.1053/j.gastro.2014.10.011]
[http://dx.doi.org/10.1371/journal.pone.0086692] [PMID: 24475168]
[http://dx.doi.org/10.1016/j.dld.2015.12.016] [PMID: 26821929]
[http://dx.doi.org/10.1080/14712598.2019.1561850] [PMID: 30571147]
[http://dx.doi.org/10.1111/j.1365-2036.2011.04612.x] [PMID: 21366636]
[http://dx.doi.org/10.1053/j.gastro.2014.05.008]
[http://dx.doi.org/10.1056/NEJMoa1602773] [PMID: 27959607]
[http://dx.doi.org/10.1080/21645515.2015.1057363] [PMID: 26110550]
[http://dx.doi.org/10.3389/fphar.2019.00212] [PMID: 30930775]
[http://dx.doi.org/10.1080/1744666X.2017.1291342] [PMID: 28164724]
[http://dx.doi.org/10.1177/1756284819848631] [PMID: 31205486]
[http://dx.doi.org/10.1056/NEJMra1202117] [PMID: 23301733]
[http://dx.doi.org/10.1146/annurev.immunol.16.1.293] [PMID: 9597132]
[http://dx.doi.org/10.1007/s11926-009-0054-9] [PMID: 19772834]
[http://dx.doi.org/10.1111/j.1600-065X.2008.00754.x] [PMID: 19290934]
[http://dx.doi.org/10.1080/1744666X.2018.1532291] [PMID: 30285500]
[http://dx.doi.org/10.1016/j.immuni.2019.03.028] [PMID: 30995502]
[http://dx.doi.org/10.1097/00130832-200212000-00004] [PMID: 14752332]
[http://dx.doi.org/10.1016/S0898-6568(98)00023-0] [PMID: 9794243]
[http://dx.doi.org/10.1016/j.molimm.2006.11.025] [PMID: 17208301]
[http://dx.doi.org/10.1038/s41577-018-0066-7] [PMID: 30254251]
[http://dx.doi.org/10.1016/j.autrev.2019.102390] [PMID: 31520803]
[http://dx.doi.org/10.1111/jdv.15489] [PMID: 30762909]
[http://dx.doi.org/10.1016/j.jid.2019.03.1142] [PMID: 31196751]
[http://dx.doi.org/10.1016/j.autrev.2018.07.014] [PMID: 30572136]
[http://dx.doi.org/10.1021/jm401490p] [PMID: 24417533]
[http://dx.doi.org/10.1056/NEJMoa1606910] [PMID: 28467869]
[http://dx.doi.org/10.1056/NEJMoa1112168] [PMID: 22894574]
[http://dx.doi.org/10.1093/ibd/izy365] [PMID: 30590590]
[http://dx.doi.org/10.1016/j.cgh.2018.07.009] [PMID: 30012431]
[PMID: 31660640]
[http://dx.doi.org/10.1136/gutjnl-2016-312735] [PMID: 28209624]
[http://dx.doi.org/10.1016/j.cgh.2014.01.029]
[http://dx.doi.org/10.1111/apt.15072] [PMID: 30663107]
[http://dx.doi.org/10.1016/S0140-6736(16)32537-5] [PMID: 27988142]
[http://dx.doi.org/10.1016/S0016-5085(17)34357-3]
[http://dx.doi.org/10.1053/j.gastro.2019.01.093]
[http://dx.doi.org/10.1056/NEJMoa1806382] [PMID: 30205746]
[http://dx.doi.org/10.1111/bjd.13745] [PMID: 25704750]
[http://dx.doi.org/10.1136/annrheumdis-2015-208279] [PMID: 26672064]
[http://dx.doi.org/10.1002/art.40054] [PMID: 28118538]
[http://dx.doi.org/10.1093/ecco-jcc/jjy085] [PMID: 29917064]
[http://dx.doi.org/10.1016/j.cgh.2018.07.013] [PMID: 30031174]
[http://dx.doi.org/10.1093/ecco-jcc/jjz013] [PMID: 30668662]
[http://dx.doi.org/10.1053/j.gastro.2018.04.012]
[http://dx.doi.org/10.1016/j.cgh.2018.11.035] [PMID: 30476584]
[http://dx.doi.org/10.1093/ibd/izy150] [PMID: 29788127]
[http://dx.doi.org/10.1002/art.38745] [PMID: 24943354]
[http://dx.doi.org/10.1093/ibd/izy131] [PMID: 29850873]
[http://dx.doi.org/10.1016/j.cgh.2019.04.059]
[http://dx.doi.org/10.1186/s13075-019-1866-2] [PMID: 30953540]
[http://dx.doi.org/10.1093/ecco-jcc/jjy164] [PMID: 30321330]
[http://dx.doi.org/10.1097/MIB.0000000000000274] [PMID: 25581828]
[http://dx.doi.org/10.1111/apt.15514] [PMID: 31599001]
[http://dx.doi.org/10.1002/art.39761] [PMID: 27213279]
[http://dx.doi.org/10.1053/j.gastro.2018.12.022] [PMID: 30658060]
[http://dx.doi.org/10.1093/ibd/izy160] [PMID: 29982686]
[http://dx.doi.org/10.1007/s40264-016-0431-z] [PMID: 27282428]
[http://dx.doi.org/10.1016/j.jinf.2017.02.009] [PMID: 28263759]