Thématique :
Originalité :
Solidité :
Très solide
Doit faire évoluer notre pratique :
Nom du veilleur :
Docteur Stéphane NAHON
Coup de coeur :
Clinical Gastroenterology and Hepatology
  2019 Jan;17(1):139-147.  
  doi: 10.1016/j.cgh.2018.07.009.  
  Tofacitinib Induction Therapy Reduces Symptoms Within 3 Days for Patients With Ulcerative Colitis.  
  Hanauer S, Panaccione R, Danese S, Cheifetz A, Reinisch W, Higgins PDR, Woodworth DA, Zhang H, Friedman GS, Lawendy N, Quirk D, Nduaka CI, Su C  



Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2).


The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein.


Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: -0.27 vs placebo: -0.11; P < .01), total number of daily bowel movements (-1.06 vs -0.27; P < .0001), and rectal bleeding subscore (-0.30 vs -0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by ≥1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by ≥1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups.


In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC. no: NCT01465763 and NCT01458951.


Question posée
Quel est le délai d’action du tofacitinib au cours de la RCH ?
Question posée
Dans ce travail post-hoc des études pivotales sur le tofacitinib, le score Mayo (sans endo) et le score de rectorragies étaient significativement plus bas dans le groupe tofacitinib versus le groupe placebo. Cet effet est observé à la fois chez les patients naïfs ou en échec des anti-TNF.

Cette analyse post-hoc est intéressante car elle laisse présager une efficacité rapide du tofacitinib, ce qui peut être intéressant chez les patients ayant un handicap fonctionnel important. A l’inverse, en cas d’inefficacité après 16 semaines, il n’est pas utile de poursuivre le traitement.