SNFGE SNFGE
 
Thématique :
- Colo-proctologie
Originalité :
Très original
Solidité :
A confirmer
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Docteur Pauline JOUET
Coup de coeur :
 
 
Gastroenterology
  2019/02  
 
  2019 Feb;156(3):592-603.e10.  
  doi: 10.1053/j.gastro.2018.10.051.  
 
  RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis.  
 
  Hirano I, Collins MH, Assouline-Dayan Y, Evans L, Gupta S, Schoepfer AM, Straumann A, Safroneeva E, Grimm M, Smith H, Tompkins CA, Woo A, Peach R, Frohna P, Gujrathi S, Penenberg DN, Li C, Opiteck GJ, Olson A, Aranda R, Rothenberg ME, Dellon ES; HEROES Study Group.  
  https://www.ncbi.nlm.nih.gov/pubmed/30395812  
 
 

Abstract

BACKGROUND & AIMS:

Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE.

METHODS:

We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation.

RESULTS:

At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P = .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P = .0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patientswith steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection.

CONCLUSIONS:

In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.

 

 
Question posée
 
L’administration sous-cutanée d’un anticorps anti-IL 13 (RPC4046) pendant 16 semaines améliore-t-elle les lésions histologiques d’œsophagite à éosinophiles ?
 
Question posée
 
Dans cette étude de phase 2 randomisée en double aveugle effectuée chez 100 patients dont 47 réfractaires aux corticoïdes, l’administration hebdomadaire de cet anti-IL13 à 180mg ou 360mg diminuait significativement l’infiltrat à éosinophiles de la muqueuse œsophagienne en comparaison au placebo, ainsi que l’importance des lésions endoscopiques, avec une bonne tolérance.
 
Commentaires

Première étude utilisant une biothérapie chez l’homme dans le traitement de l’œsophagite à éosinophiles avec des résultats très prometteurs, méritant bien sûr confirmation par une étude de phase 3.

 
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