Abstract
Patients with inflammatory bowel diseases (IBD) have an increased risk of thrombosis. The interaction between inflammation and coagulation has extensively been studied. It is well-- known that some drugs can influence the haemostatic system, but several concerns on the association between therapies and increased risk of thrombosis remain open. While biologics seem to have a protective role against thrombosis via their anti-inflammatory effect, some concerns about an increased risk of thrombosis with JAK inhibitors have been raised. We conducted a literature review to assess the association between biologics/small molecules and venous/arterial thrombotic complications. An increased risk of venous and arterial thrombosis was found in patients treated with corticosteroids, whereas anti-TNFα were considered protective agents. No thromboembolic adverse event was reported with vedolizumab and ustekinumab. In addition, thromboembolic events rarely occurred in patients with ulcerative colitis (UC) after therapy with tofacitinib. The overall risk of both venous and arterial thrombosis was not increased based on the available evidence. Finally, in the era of JAK inhibitors, the treatment should be individualized by evaluating the pre-existing potential thrombotic risk balanced with the intrinsic risk of the medication used.
Keywords: Inflammatory bowel disease, thrombosis, corticosteroids, anti-TNFα, vedolizumab, ustekinumab, JAK inhibitors
Graphical Abstract
[http://dx.doi.org/10.1111/j.1572-0241.2008.02052.x] [PMID: 18684186]
[http://dx.doi.org/10.1055/s-0037-1615600] [PMID: 11307809]
[http://dx.doi.org/10.1136/gut.2010.228585] [PMID: 21339206]
[http://dx.doi.org/10.1111/apt.12294] [PMID: 23550660]
[http://dx.doi.org/10.1177/1076029609360528] [PMID: 20211927]
[http://dx.doi.org/10.1016/j.crohns.2013.09.021] [PMID: 24183231]
[http://dx.doi.org/10.1111/j.1572-0241.2006.00943.x] [PMID: 17100967]
[http://dx.doi.org/10.1111/j.1572-0241.2003.07491.x] [PMID: 12818264]
[http://dx.doi.org/10.1007/s11239-008-0244-8] [PMID: 18685811]
[http://dx.doi.org/10.3748/wjg.v20.i17.4857] [PMID: 24803797]
[http://dx.doi.org/10.1016/S0140-6736(09)61963-2] [PMID: 20149425]
[http://dx.doi.org/10.1053/j.gastro.2010.05.026] [PMID: 20546736]
[http://dx.doi.org/10.1371/journal.pone.0056944] [PMID: 23457642]
[http://dx.doi.org/10.1111/j.1365-2036.2011.04864.x] [PMID: 21967576]
[http://dx.doi.org/10.1111/jgh.12260] [PMID: 23662785]
[http://dx.doi.org/10.1136/gutjnl-2017-314015] [PMID: 28647686]
[http://dx.doi.org/10.1016/j.cgh.2014.07.017] [PMID: 25038374]
[http://dx.doi.org/10.1001/jamainternmed.2013.122] [PMID: 23546607]
[http://dx.doi.org/10.1136/gutjnl-2012-303285] [PMID: 22961677]
[http://dx.doi.org/10.1080/1744666X.2017.1291342] [PMID: 28164724]
[http://dx.doi.org/10.1056/NEJMoa1606910] [PMID: 28467869]
[http://dx.doi.org/10.1177/1076029616632906] [PMID: 26893444]
[http://dx.doi.org/10.1177/1076029611405034] [PMID: 21593018]
[http://dx.doi.org/10.1016/j.cgh.2019.12.043] [PMID: 31972287]
[http://dx.doi.org/10.1038/nrgastro.2016.208] [PMID: 28144028]
[http://dx.doi.org/10.1002/ibd.21334] [PMID: 20848518]
[http://dx.doi.org/10.1111/j.1538-7836.2010.04034.x] [PMID: 20735729]
[http://dx.doi.org/10.1084/jem.163.3.740] [PMID: 3753996]
[http://dx.doi.org/10.1002/ibd.21593] [PMID: 21987296]
[http://dx.doi.org/10.4049/jimmunol.176.4.2617] [PMID: 16456024]
[http://dx.doi.org/10.1038/s41416-018-0045-6] [PMID: 29545596]
[http://dx.doi.org/10.1021/acschembio.0c00076] [PMID: 32176847]
[http://dx.doi.org/10.1042/BCJ20190038] [PMID: 30782972]
[http://dx.doi.org/10.2174/138945007780058979] [PMID: 17348832]
[http://dx.doi.org/10.2174/138945011701151217100907] [PMID: 25330032]
[PMID: 32410551]
[http://dx.doi.org/10.3109/08977194.2012.660936] [PMID: 22339650]
[http://dx.doi.org/10.3389/fphar.2019.00212] [PMID: 30930775]
[http://dx.doi.org/10.1038/nrrheum.2017.23] [PMID: 28250461]
[http://dx.doi.org/10.1007/s11926-018-0752-2] [PMID: 29846814]
[http://dx.doi.org/10.1097/MEG.0000000000000495] [PMID: 26513610]
[http://dx.doi.org/10.1093/ecco-jcc/jjx162] [PMID: 29220427]
[http://dx.doi.org/10.1097/MIB.0000000000000301] [PMID: 25659086]
[http://dx.doi.org/10.1097/MCG.0000000000001290] [PMID: 31789759]
[http://dx.doi.org/10.3748/wjg.v24.i23.2457] [PMID: 29930467]
[http://dx.doi.org/10.1093/ecco-jcc/jjx079] [PMID: 28575273]
[http://dx.doi.org/10.1136/gutjnl-2016-312735] [PMID: 28209624]
[http://dx.doi.org/10.1080/1744666X.2018.1512404] [PMID: 30118353]
[http://dx.doi.org/10.1111/apt.15514] [PMID: 31599001]
[http://dx.doi.org/10.1007/s40264-017-0622-2] [PMID: 29196988]
[http://dx.doi.org/10.1002/art.40798] [PMID: 30552833]
[http://dx.doi.org/10.1007/s40265-017-0723-3] [PMID: 28290136]
[http://dx.doi.org/10.1002/art.40841] [PMID: 30663869]
[http://dx.doi.org/10.1080/13543784.2018.1492547] [PMID: 29938545]
[http://dx.doi.org/10.1007/s40265-019-01211-z] [PMID: 31642025]
[http://dx.doi.org/10.1016/S0140-6736(18)31116-4] [PMID: 29908670]
[http://dx.doi.org/10.1053/j.gastro.2020.02.030] [PMID: 32092309]
[http://dx.doi.org/10.1136/annrheumdis-2018-214846] [PMID: 31088790]
[http://dx.doi.org/10.1007/s40259-018-0304-3] [PMID: 30203252]
[http://dx.doi.org/10.1177/1759720X19895492] [PMID: 31897092]
[http://dx.doi.org/10.1155/2012/175249] [PMID: 23166902]
[http://dx.doi.org/10.1007/s10620-012-2435-6] [PMID: 23053902]
[http://dx.doi.org/10.1097/MCG.0b013e31824c0dea] [PMID: 22476043]
[http://dx.doi.org/10.1080/00365521.2017.1278785] [PMID: 28128675]
[http://dx.doi.org/10.3748/wjg.14.4440] [PMID: 18680221]
[http://dx.doi.org/10.1053/j.gastro.2014.01.042] [PMID: 24462530]
[http://dx.doi.org/10.1136/gutjnl-2019-318448] [PMID: 31227590]
[http://dx.doi.org/10.1182/bloodadvances.2018024828] [PMID: 30482764]
[http://dx.doi.org/10.7326/0003-4819-146-4-200702200-00007] [PMID: 17310052]
[http://dx.doi.org/10.1016/j.cgh.2014.02.034] [PMID: 24632349]
[http://dx.doi.org/10.1016/j.crohns.2013.09.007] [PMID: 24095288]
[http://dx.doi.org/10.1097/DCR.0b013e3182698f60] [PMID: 23044674]
[http://dx.doi.org/10.1378/chest.11-2298]
[http://dx.doi.org/10.1093/ecco-jcc/jjv213] [PMID: 26614685]
[http://dx.doi.org/10.14309/ajg.0000000000000152] [PMID: 30840605]
[http://dx.doi.org/10.1055/s-0033-1343886] [PMID: 23629820]
[http://dx.doi.org/10.1016/j.crohns.2012.09.005] [PMID: 23040453]
[http://dx.doi.org/10.1016/j.crohns.2009.12.002] [PMID: 21122489]
[http://dx.doi.org/10.1038/ajg.2013.220] [PMID: 23857476]
[http://dx.doi.org/10.1016/j.crohns.2013.03.002] [PMID: 23537817]
[http://dx.doi.org/10.1038/ajg.2017.479] [PMID: 29336432]
[http://dx.doi.org/10.1038/nrgastro.2014.202] [PMID: 25446727]
[http://dx.doi.org/10.1016/j.jacc.2019.03.010] [PMID: 30894318]