SNFGE SNFGE
 
Thématique :
- MICI
Originalité :
Intermédiaire
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Immédiatement
 
 
Nom du veilleur :
Professeur Philippe SEKSIK
Coup de coeur :
 
 
Gastroenterology
  2018/10  
 
  2018 Oct;155(4):1045-1058.  
  doi: 10.1053/j.gastro.2018.06.035.  
 
  Efficacy of Ustekinumab for Inducing Endoscopic Healing in Patients With Crohn's Disease.  
 
  Rutgeerts P, Gasink C, Chan D, Lang Y, Pollack P, Colombel JF, Wolf DC, Jacobstein D, Johanns J, Szapary P, Adedokun OJ, Feagan BG, Sandborn WJ  
  https://www.ncbi.nlm.nih.gov/pubmed/29909019  
 
 

Abstract

BACKGROUND & AIMS:

We evaluated the ability of ustekinumab, a monoclonal antibody against the p40 subunit of interleukins 12 and 23, to induce endoscopic healing in patients with moderate to severe Crohn's disease (CD).

METHODS:

We performed an endoscopy substudy of 334 patients with moderate to severe CD participating in 3 randomized controlled phase 3 studies to determine the safety and efficacy of ustekinumab induction and maintenance therapy. All patients underwent colonoscopy at baseline and week 8 of the induction studies and at week 44 of the maintenance study; all colonoscopies were assessed by a blinded central reader. During the induction studies, patients were randomly assigned to groups given intravenous ustekinumab (130 mg or 6 mg/kg) or placebo. At the baseline time point of the maintenance study (week 8 of the induction studies), patients with a clinical response to ustekinumab were randomly assigned to groups given subcutaneous ustekinumab (90 mg every 12 weeks or 8 weeks) or placebo. Additional maintenance analysis populations were patients who did not respond to ustekinumab or placebo during the induction studies, and patients who responded to placebo during the induction studies; we performed a post-hoc pooled analysis of randomly assigned and non-randomly assigned patients of the maintenance study. We analyzed data from patients with an ulcer in at least 1 segment at baseline of the induction studies. The primary end point was change in the Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD), from baseline, at week 8. We also assessed the efficacy of maintenance therapy.

RESULTS:

Patients given ustekinumab had a greater reduction in SES-CD from the induction baseline time point until week 8 than placebo (reduction of 2.8 in patients given ustekinumab vs a reduction of 0.7 points in patients given placebo; P = .012). Results were similar among patients in different induction studies and patients given different doses of ustekinumab. At week 44, reductions in the SES-CD from the induction baseline were greater in patients given ustekinumab (for combined groups, a reduction of 2.5; P = .176 and for every 8 weeks, a reduction of 3.1; P = .107) than patients given placebo (reduction of 1.9 points). Maintenance results were similar for the larger pooled post-hoc analysis.

CONCLUSIONS:

In an analysis of data from 3 trials of patients with moderate to severe CD, ustekinumab (intravenous induction and subcutaneous maintenance) reduces SES-CD compared with placebo. We observed significant reductions in endoscopic disease activity at week 8 of induction therapy with ustekinumab. (ClinicalTrials.gov numbers, NCT01369329NCT01369342, and NCT01369355).

 
 
Question posée
 
Quel effet l’ustekinumab a-t-il sur la cicatrisation muqueuse ?
 
Question posée
 
L’ustékinumab (dose de charge IV 130 mg ou 6 mg/kg puis dose d’entretien en sous-cutané 90mg/ 12 ou 8 semaines) fait mieux que le placebo en terme de cicatrisation muqueuse à la semaine 8 et à la semaine 44.
 
Commentaires

Cette sous-étude issue des essais pivotaux montrant l’efficacité clinique de l’ustekinumab dans la maladie de Crohn est de faible effectif surtout dans le groupe placebo (49 patients). Cette sous-étude est basée sur le volontariat des patients et peut être polluée par un biais de participation.

 
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