[en] BACKGROUND: While ulcerative proctitis (UP) can dramatically impair quality-of-life, treatments efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomized controlled trials in ulcerative colitis. AIM: To assess the effectiveness and safety of tofacitinib for the treatment of UP. METHODS: We conducted a retrospective multicenter study in seventeen GETAID centers including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between week 8 and week 14, defined as a partial Mayo score of 2 (and no individual subscore above 1). Secondary outcomes included clinical response and steroid-free remission after induction and at one year. RESULTS: All the 35 enrolled patients previously received anti-TNF therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (IQR[5.5-7]). After induction (W8-W14), 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At one year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, while 51.2% (17/33) were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95%CI[35.5-71.6]) at one year. Only a lower partial Mayo at baseline was independently associated with remission at induction (Odds ratio (OR) = 0.56 for an increase of 1, 95% confidence interval (95%CI) [0.33-0.95], p = 0.03). Five (14.3%) adverse events were reported with one leading to treatment withdrawal (septic shock secondary to cholecystitis). CONCLUSION: Tofacitinib may offer a therapeutic option for patients with refractory UP.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Uzzan, Mathieu ; Paris Est Créteil University UPEC, Assistance Publique-Hôpitaux de Paris (AP-HP), Henri Mondor Hospital, Gastroenterology department, Fédération Hospitalo-Universitaire TRUE InnovaTive theRapy for immUne disordErs, Créteil F-94010, France.
Nachury, Maria; Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France.
Nuzzo, Alexandre; Department of Gastroenterology, Hopital Beaujon , AP-HP, Universite de Paris, France.
Amiot, Aurélien; Department of Gastroenterology, Hopitaux Universitaires Bicêtre, AP-HP, Universite Paris Est Creteil and Universite Paris Saclay, INSERM, Centre for Research in Epidemiology and Population Health, Le Kremlin Bicêtre, France.
Caron, Bénédicte; Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France and INSERM, NGERE, University of Lorraine, F-54000 Nancy, France.
Benezech, Alban; Department of Gastroenterology, Centre Hospitalier Avignon, France.
Buisson, Anthony ; Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Service d'Hépato-Gastroentérologie, Clermont-Ferrand, France , Université Clermont Auvergne, Inserm U1071, M2iSH, USC-INRA 2018, F-63000 Clermont-Ferrand, France.
Bouguen, Guillaume; Department of Gastroenterology, CHU Renes, France.
Le Berre, Catherine; Institut des Maladies de l'Appareil Digestif (IMAD), Hépato-Gastro-Entérologie et Assistance Nutritionnelle, Inserm CIC 1413, Inserm UMR 1235, Nantes Université, CHU Nantes, F-44000 Nantes, France.
Reenaers, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive
Le Cosquer, Guillaume; Department of Gastroenterology and Pancreatology, Hôpital Rangueil, CHU de Toulouse, Université Toulouse Paul Sabatier, Toulouse, France.
Savoye, Guillaume; CHU Rennes, University Rennes, INSERM, CIC1414, Institute NUMECAN (Nutrition Metabolism and Cancer), 35000 Rennes, France.
Charkaoui, Maeva; Department of Hepatogastroenterology, Dijon University Hospital, F 21000 Dijon, France.
Vidon, Mathias; Departement of Gastroenterology. Hopital Intercommunal de Créteil, Créteil France.
Guillo, Lucas; Department of Gastroenterology, University Hospital of Marseille Nord, University of Aix-Marseille, Marseille, France.
Fumery, Mathurin ; Department of Gastroenterology, Amiens University Hospital, and UMR I01, PERITOX, Jules Verne University of Picardy, F-80000 Amiens, France.
Peyrin-Biroulet, Laurent; Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France and INSERM, NGERE, University of Lorraine, F-54000 Nancy, France.
Kirchgesner, Julien ; INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Department of Gastroenterology, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
Bouhnik, Yoram; Paris IBD Center, Groupe Hospitalier Privé Ambroise Paré - Hartmann, Neuilly sur Seine, 92200 France.
Meucci G, Vecchi M, Astegiano M, et al. The natural history of ulcerative proctitis: a multicenter, retrospective study. Am J Gastroenterol 2000;95:469–73. doi:10.1111/j.1572-0241.2000. t01-1-01770.x.
Jess T, Riis L, Vind I, et al. Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark. Inflamm Bowel Dis 2007;13:481–9. doi:10.1002/ibd.20036.
Kim B, Park SJ, Hong SP, Kim TI, Kim WH, Cheon JH. Proximal disease extension and related predicting factors in ulcerative proctitis. Scand J Gastroenterol 2014;49:177–83. doi:10.3109/003655 21.2013.867360.
Pineton de Chambrun G, Tassy B, Kollen L, et al. The treatment of refractory ulcerative colitis. Best Pract Res Clin Gastroenterol 2018;49:57. doi:10.1016/j.bpg.2018.05.009.
Dubois E, Moens A, Geelen R, Sabino J, Ferrante M, Vermeire S. Long-term outcomes of patients with ulcerative proctitis: Analysis from a large referral centre cohort. United Eur Gastroenterol J 2020;8:933–41. doi:10.1177/2050640620941345.
Caron B, Sandborn WJ, Schreiber S, Panaccione R, Danese S, Peyrin-Biroulet L. Drug development for ulcerative proctitis: current concepts. Gut 2021;70:1203–9. doi:10.1136/gutjnl-2021-324108.
Caron B, Abreu MT, Siegel CA, et al. IOIBD recommendations for clinical trials in ulcerative proctitis: the proctrial consensus. Clin Gastroenterol Hepatol 2022;20:2619–27.e1. doi:10.1016/j. cgh.2022.02.032.
Pineton de Chambrun G, Amiot A, Bouguen G, et al.; PROTECT-GETAID study group. Efficacy of tumor necrosis factor antagonist treatment in patients with refractory ulcerative proctitis. Clin Gastroenterol Hepatol 2020;18:620–7.e1. doi:10.1016/j. cgh.2019.05.060.
Mallet AL, Bouguen G, Conroy G, et al. Azathioprine for refractory ulcerative proctitis: a retrospective multicenter study. Dig Liver Dis 2017;49:280–5. doi:10.1016/j.dld.2016.12.001.
Lawrance IC, Baird A, Lightower D, Radford-Smith G, Andrews JM, Connor S. Efficacy of rectal tacrolimus for induction therapy in patients with resistant ulcerative proctitis. Clin Gastroenterol Hepatol 2017;15:1248–55. doi:10.1016/j.cgh.2017.02.027.
Monstad IL, Solberg IC, Cvancarova M, et al. Outcome of ulcerative colitis 20 years after diagnosis in a prospective population-based inception cohort from South-Eastern Norway, the IBSEN study. J Crohns Colitis 2021;15:969–79. doi:10.1093/ecco-jcc/ jjaa232.
Peyrin-Biroulet L, Dubinsky MC, Sands BE, et al. P407 Efficacy and safety of etrasimod in subjects with moderately to severely active isolated proctitis: a subgroup analysis of the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. J Crohns Colitis 2023;17:i536–8. doi:10.1093/ecco-jcc/jjac190.0537.
Sandborn WJ, Su C, Panes J. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2017;496:7. doi:10.1056/NEJMc1707500.
Magro F, Gionchetti P, Eliakim R, et al.; European Crohn’s and Colitis Organisation [ECCO]. Third European evidence-based consensus on diagnosis and management of ulcerative colitis part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis 2017;11:649–70. doi:10.1093/ecco-jcc/jjx008.
Haute Autorité de Santé. XELJANZ [Tofacitinib]. 2019. https://www.has-sante.fr/jcms/c_2912419/fr/xeljanz-tofacitinib Accessed May 7, 2023.
Raine T, Bonovas S, Burisch J, et al. ECCO guidelines on therapeutics in ulcerative colitis: medical treatment. J Crohns Colitis 2021;16:2–17. doi:10.1093/ecco-jcc/jjab178.
Lie MRKL., Kreijne JE, Dijkstra G, et al.; Dutch Initiative on Crohn and Colitis. No superiority of tacrolimus suppositories vs beclomethasone suppositories in a randomized trial of patients with refractory ulcerative proctitis. Clin Gastroenterol Hepatol 2020;18:1777–84.e2. doi:10.1016/j.cgh.2019.09.049.
Caron B, Sandborn WJ, Panaccione R, et al. Efficacy of pharmacological agents for ulcerative proctitis: a systematic literature review. J Crohns Colitis 2022;16:922–30. doi:10.1093/ecco-jcc/jjab218.
Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis [ELEVATE]: two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet 2023;401:1159–71. doi:10.1016/s0140-6736[23]00061-2.
Sandborn WJ, Su C, Sands BE, et al.; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2017;376:1723–36. doi:10.1056/nejmoa1606910.
