[Biotherapies for the treatment of ulcerative colitis]. / Biothérapies dans le traitement de la rectocolite hémorragique.

BIOTHÉRAPIES DANS LE TRAITEMENT DE LA RECTOCOLITE HÉMORRAGIQUE. Le traitement de la rectocolite hémorragique a considérablement évolué puisqu'il doit, pour la plupart des patients,permettre une cicatrisation des lésions inflammatoires coliques et non plus une simple rémission des symptômes cliniques. Ceci est désormais possible grâce aux biothérapies dont trois classes principales sont autorisées dans la rectocolite hémorragique. Les anti-TNF, classe la plus ancienne, ont fait la preuve de leur efficacité et peuvent être utilisés en première ligne de traitement après échec des traitements conventionnels. Parmi eux, seul l'infliximab est recommandé dans les colites aiguës graves. Le védolizumab, anti-intégrine, peut également être utilisé en première ligne, avec un excellent profil de tolérance mais pas d'effet sur les manifestations extradigestives. Les anti-interleukines 12 et 23 (ustékinumab), bientôt rejointes par d'autres anticorps spécifiques de l'interleukine 23, sont également très efficaces et leur tolérance excellente, mais se positionnent en échec d'une première ligne de biothérapie. S'ajoutent à cet arsenal les inhibiteurs de JAK, petites molécules orales, d'action très puissante mais dont le profil médiocre de tolérance les réserve aux sujets jeunes, sans comorbidité et généralement après échec de deux lignes de biothérapie. Tous ces traitements sont actuellement disponibles à domicile, par voie sous-cutanée, ou orale pour les inhibiteurs de JAK. Ceci implique pour les patients une bonne connaissance, acquise par l'éducation thérapeutique, et la mise en place d'un suivi coordonné avec tous les acteurs de soins : gastroentérologues, médecins généralistes et infirmières de coordination.

BIOTHERAPIES FOR THE TREATMENT OF ULCERATIVE COLITIS. The treatment of ulcerative colitis has evolved considerably since it must, for most patients, allow healing of inflammatory colonic lesions and no longer a simple remission of clinical symptoms. This is now possible thanks to biotherapies, of which three main classes are authorized in ulcerative colitis. Anti-TNFs, the oldest class, have proven their effectiveness and can be used as first-line treatment after failure of conventional treatments. Among them, only infliximab is recommended in severe acute colitis. Vedolizumab, anti-integrin, can also be used in first line with an excellent safety profile but no effect on extradigestive manifestations. The anti-interleukin 12/23 ustekinumab, soon joined by other antibodies specific for interleukin 23, is also very effective and its tolerance excellent, but is positioned after a failure of a first biologic. Janus kinase (JAK) inhibitors, small oral molecules, with a very powerful action, but whose poor tolerance profile reserves them for young subjects, without comorbidity and generally after failure of two lines of biologics. All these treatments are currently available at home, by subcutaneous route, or orally for JAK inhibitors. This implies their good knowledge and the implementation of patient follow-up coordinated with all healthcare providers: gastroenterologists, general practitioners and IBD coordinating nurses.

Preclinical Model of Perianal Fistulizing Crohn's Disease.

BACKGROUND: Fistulizing anoperineal lesions (FAPLs) are common and severe complications of Crohn's disease (CD), exposing patients to the risk of anal sphincter alteration and permanent stoma. Due to the limited efficacy of current treatments, identifying new local therapies is mandatory. However, testing new treatments is currently limited because no relevant preclinical model of Crohn's-like FAPL is available. Thus, a reliable and reproducible experimental model of FAPLs is needed to assess new therapeutic strategies. METHODS: Twenty-one rats received a rectal enema of 2,4,6-trinitrobenzensulfonic acid (TNBS) to induce proctitis. Seven days later, a transsphincteric fistula tract was created with a surgical thread, instilled with TNBS twice a week until its removal at day 7 (group 1), day 14 (group 2), or day 28 (group 3). In each rat, pelvic MRI was performed just before and 7 days after thread removal. Rats were sacrificed 7 days after thread removal for pathological assessment of the fistula tract. RESULTS: The optimal preclinical model was obtained in group 3. In this group, 7 days after thread removal, all animals (9 of 9) had a persistent fistula tract visible on MRI with T2-hypersignal (normalized T2 signal intensity: 2.36 ± 0.39 arbitrary units [a.u.] [2.08-2.81]) and elevation of the apparent diffusion coefficient (1.33 ± 0.16 10-3 millimeter squared per seconds [1.18-1.49]). The pathological examination of the fistula tract revealed acute and chronic inflammation, granulations, fibrosis, epithelialization, and proctitis in the adjacent rectum. CONCLUSIONS: This reproducible preclinical model could be used to assess the effectiveness of innovative treatments in perianal fistulizing CD.