Thématique :
Originalité :
Solidité :
Très solide
Doit faire évoluer notre pratique :
Dans certains cas
Nom du veilleur :
Professeur Philippe MARTEAU
Coup de coeur :
The Lancet
  2015 Sep 2. pii: S0140-6736(15)00068-9  
  doi: 10.1016/S0140-6736(15)00068-9  
  Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial  
  Khanna R, Bressler B, Levesque BG, Zou G, Stitt LW, Greenberg GR, Panaccione R, Bitton A, Paré P, Vermeire S, D'Haens G, MacIntosh D, Sandborn WJ, Donner A, Vandervoort MK, Morris JC, Feagan BG; REACT Study Investigators  

Conventional management of Crohn's disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohn's disease.

In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohn's Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohn's disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohn's disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤4) at 12 months at the practice level. This trial is registered with, number NCT01030809.

This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95% CI −5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference [AD] 7·3%, hazard ratio [HR]: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events.

Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality.

AbbVie Pharmaceuticals.

Question posée
Faut il traiter avec escalade thérapeutique progressive comme à l’habitude ou traiter d’emblée les maladies de Crohn par une combothérapie d’anti-TNF et d’immunosuppresseur ?
Question posée
Le résultat sur l’efficacité est le même avec les deux attitudes. Un moindre risque de complications graves dans le groupe combothérapie est aussi observé.

Cette étude incluant beaucoup de malades dans des pays différents est bien faite et nous renseigne sur des conditions de « vraie vie ». Les résultats n’ont pas un niveau de preuve indiscutable et susciteront donc encore débat sur que faire face à ces malades et la nécessité d’études.