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- Title
Petites molécules et sécurité d'emploi dans les MICI.
- Authors
Roblin, Xavier; Barrau, Mathilde; Peaucelle, Anne-Sophie; Paul, Stéphane; Mathieu, Nicolas
- Abstract
Small molecules include selective and non-selective JAK inhibitors (tofacitinib, upadacitinib and filgotinib), all of which are reimbursed as third-line biotherapy in UC. Only upadacitinib is reimbursed in Crohn's disease, as a second-line treatment after failure of an anti-TNF agent. On the other hand, small molecules include the class of S1P modulators, ozanimod and etrasimod, which have obtained European marketing authorization in UC. An increased risk of cancer has been described with tofacitinib or anti-TNF in rheumatoid arthritis patients over 50 with cardiovascular risk factors. Extensive North American retrospective health data show no excess risk of cancer with small molecules compared to biotherapy. According to HAS (Haute Autorité de Santé) recommendations, this family of JAK inhibitors should be used with great caution in patients with thromboembolic risk factors, and in particular in patients with a history of thromboembolism. A positive study has been carried out on thromboembolic recurrence rates in relation to the use of anticoagulants. These results must be confirmed in a study of IBD that takes into account patients' inflammatory activity. HAS recommends that JaK inhibitors should not be offered to high-risk patients (over 65 years of age, smokers, history of other cardiovascular risk factors). Furthermore, IBD is an independent risk factor for vascular events, which are now considered as extra-intestinal manifestations of the disease. Registry data suggest a lower incidence of thromboembolic events in low-risk populations with biotherapies and JAK inhibitors. ECCO (European Crohn's and Colitis Organisation) guidelines suggest that JAK inhibitors and S1P modulators should not be used during pregnancy. Current data in the literature describe 165 pregnancies with exposure to tofacitinib, 31 of which were for IBD, with no major alerts. The levels of evidence are still insufficient to change our current precautionary recommendations.
- Subjects
CROHN'S disease; CARDIOVASCULAR diseases risk factors; DISEASE risk factors; INFLAMMATORY bowel diseases; SMALL molecules
- Publication
Hépato-Gastro & Oncologie Digestive, 2024, Vol 31, Issue 10, p1107
- ISSN
2115-3310
- Publication type
Academic Journal
- DOI
10.1684/hpg.2024.2888