Thématique :
Originalité :
Solidité :
Doit faire évoluer notre pratique :
Nom du veilleur :
Docteur Stéphane NAHON
Coup de coeur :
Clinical Gastroenterology and Hepatology
  2016 Apr;14(4):550-557.e2  
  doi: 10.1016/j.cgh.2015.10.025  
  Optimizing Anti-TNF-α Therapy: Serum Levels of Infliximab and Adalimumab Are Associated With Mucosal Healing in Patients With Inflammatory Bowel Diseases.  
  Ungar B, Levy I, Yavne Y, Yavzori M, Picard O, Fudim E, Loebstein R, Chowers Y, Eliakim R, Kopylov U, Ben-Horin S  


It is not clear what serum levels of anti-tumor necrosis factor are associated with reduced intestinal inflammation in patients with inflammatory bowel disease (IBD). We aimed to identify serum levels of infliximab and adalimumab associated with mucosal healing in patients with IBD and to evaluate the putative gain in control of inflammation by incremental increases in drug levels.


We performed a retrospective cross-sectional study of 145 patients with IBD treated with infliximab (n = 78) or adalimumab (n = 67) at a medical center in Israel from 2009 through 2014. We collected data from colonoscopy examinations; mucosal healing was defined as simple endoscopic score of <3 or a Mayo score ≤1. These data were compared with serum levels of anti-tumor necrosis factor agents, clinical scores, and levels of C-reactive protein.


Median serum levels of infliximab and adalimumab were significantly higher in patients with mucosal healing than patients with active disease (based on endoscopy) (for infliximab, 4.3 vs 1.7 μg/mL, P = .0002; for adalimumab, 6.2 vs 3.1 μg/mL, P = .01). Levels of infliximab above 5 μg/mL (area under the curve = 0.75; P < .0001) and levels of adalimumab above 7.1 μg/mL (area under the curve = 0.7; P = .004) identified patients with mucosal healing with 85% specificity. Increasing levels of infliximab beyond 8 μg/mL produced only minimal increases in the rate of mucosal healing, whereas the association between higher level of adalimumab and increased rate of mucosal healing reached a plateau at 12 μg/mL. In patients with measurable levels of infliximab >3 μg/mL, the presence of antibodies to infliximab was associated with a lower rate of mucosal healing compared with patients with similar drug level without antibodies (16% vs 50%, respectively; P = .003).


In a retrospective study, we found significant association between serum levels of anti-tumor necrosis factor agents and level of mucosal healing. We propose that serum levels of 6-10 μg/mL for infliximab and 8-12 μg/mL for adalimumab are required to achieve mucosal healing in 80%-90% of patients with IBD, and that this could be considered as a "therapeutic window." Exceeding these levels produces only a negligible gain in proportion of patients with mucosal healing.

Question posée
Les taux sériques d’IFX et d’ADA sont-ils associés à la cicatrisation muqueuse au cours de la maladie de Crohn et de la RCH ?
Question posée
Dans ce travail rétrospectif, les taux sériques d’IFX (6-10 μg/mL) et d’ADA (8-12 μg/mL) étaient associés à une cicatrisation de la muqueuse définie par un score SES <3 (maladie de Crohn) ou score Mayo endoscopique ≤ 1 (RCH).

Ce travail montre que les taux sériques d’IFX et ADA sont corrélés à la CM. L’optimisation des anti-TNF en fonction des seuils définis devrait permettre :1) de diminuer les doses pour les patients au dessus du seuil de 10 μg/mL pour l’IFX et de de 12 μg/mL pour l’ADA et 2) d’augmenter les doses si IFX < 6 et ADA < 8 dans le but d’obtenir une cicatrisation muqueuse.