SNFGE SNFGE
 
Thématique :
- Colo-proctologie
Originalité :
Intermédiaire
Solidité :
Intermédiaire
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Professeur Philippe DUCROTTE
Coup de coeur :
 
 
Gut
  2017/08  
 
  2017 Aug;66(8):1403-1413.  
  doi: 10.1136/gutjnl-2015-310683  
 
  The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS.  
 
  Tack J, Schumacher K, Tonini G, Scartoni S, Capriati A, Maggi CA; and the Iris-2 investigators.  
  http://gut.bmj.com/content/early/2016/04/15/gutjnl-2015-310683  
 
 

Abstract

Background Tachykinins have been implicated in the pathophysiology of IBS with diarrhoea (IBS-D). Our aim was to study the efficacy and safety of ibodutant, a selective neurokinin-2 (NK2) receptor antagonist, in patients with IBS-D.

Methods This multinational double-blind, placebo-controlled study recruited 559 patients with IBS-D according to Rome III criteria. After a 2-week treatment-free run-in, patients were randomised to ibodutant 1 mg, 3 mg, 10 mg or placebo once daily for eight consecutive weeks. Responders were those with a combined response of satisfactory relief (weekly binary question yes/no) of overall IBS symptoms and abdominal pain/discomfort on ≥75% weeks (primary end point). Secondary end points included abdominal pain and stool pattern. Data were also analysed according to US Food and Drug Administration (FDA)-approved interim end points (improvement of pain and stool consistency). Safety was assessed by monitoring adverse events and laboratory tests. Prespecified statistical analysis involved the whole group as well as gender subgroups.

Results Demographics and baseline characteristics were comparable for all treatment arms. In the overall population, responsiveness tended to increase with escalating ibodutant doses. In the prespecified analysis by gender, ibodutant 10 mg demonstrated significant superiority over placebo in females (p=0.003), while no significant effect occurred in males. This was confirmed for secondary end points and for the responder analysis according to FDA-approved end points. The tolerability and safety of ibodutant was excellent at all doses.

Conclusions Ibodutant showed dose-dependent efficacy response in IBS-D, reaching statistical significance at the 10 mg dose in female patients. The safety and tolerability profile of ibodutant was similar to placebo.

 
Question posée
 
Les antagonistes des tachykinines peuvent-ils être une nouvelle solution thérapeutique efficace et sûre dans le syndrome de l’intestin irritable à forme diarrhéique ?
 
Question posée
 
Oui pour l’ibodutant (antagoniste sélectif des récepteurs de la neurokinine 2) mais seulement chez la femme et à dose suffisante (10 mg/jour en 1 prise)
 
Commentaires

L’essai a retenu les critères de réponse de l’EMA et de la FDA. L’effet est plus net sur le transit et la consistance des selles que sur la douleur abdominale et l'idobutant n’est pas efficace chez l’homme. La différence entre idobutant et placebo est en partie liée à un taux de répondeurs sous placebo (24.4 %) inférieur à celui prévu (40 %) alors de 46.8 % des malades répondent sous ibodutant 10 mg.

 
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