SNFGE SNFGE
 
Thématique :
- Foie
Originalité :
Très original
Solidité :
Très solide
Doit faire évoluer notre pratique :
Dans certains cas
 
 
Nom du veilleur :
Professeur Christine SILVAIN
Coup de coeur :
 
 
Hepatology
  2019/02  
 
  2019 Feb;69(2):684-698.  
  doi: 10.1002/hep.30237.  
 
  Simtuzumab for Primary Sclerosing Cholangitis: Phase 2 Study Results With Insights on the Natural History of the Disease.  
 
  Muir AJ, Levy C, Janssen HLA, Montano-Loza AJ, Shiffman ML, Caldwell S, Luketic V, Ding D, Jia C, McColgan BJ, McHutchison JG, Mani Subramanian G, Myers RP, Manns M, Chapman R, Afdhal NH, Goodman Z, Eksteen B, Bowlus CL; GS-US-321-0102 Investigators.  
  https://www.ncbi.nlm.nih.gov/pubmed/30153359  
 
 

Abstract

Lysyl oxidase like-2 (LOXL2) plays a central role in fibrogenesis and is elevated in the serum and liver of patients with primary sclerosing cholangitis (PSC). We evaluated the safety and efficacy of simtuzumab, a monoclonal antibody directed against LOXL2, in patients with PSC. Patients with compensated liver disease caused by PSC were randomized 1:1:1 to receive weekly subcutaneous injections of simtuzumab 75 mg, simtuzumab 125 mg, or placebo for 96 weeks. The primary efficacy endpoint was mean change in hepatic collagen content assessed by morphometry between baseline and week 96. Additional endpoints included change in Ishak fibrosis stage and the frequency of PSC-related clinical events. Overall, 234 patients were randomized and started treatment. At week 96, the mean change from baseline in hepatic collagen content was -0.5% for patients receiving simtuzumab 75 mg (P = 0.73 versus placebo), +0.5% for patients receiving simtuzumab 125 mg (P = 0.33 versus placebo), and 0.0 for patients receiving placebo. Compared with placebo, neither dose of simtuzumab led to significant reductions in Ishak fibrosis stage, progression to cirrhosis, or frequency of clinical events. Overall, 80 (34%) patients had fibrosis progression and 47 (20%) experienced PSC-related clinical events. In a multivariate model of baseline factors, PSC-related clinical events were more frequent in patients with advanced fibrosis (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.02-4.06; P = 0.045), higher alkaline phosphatase (HR per 10 U/L, 1.01; 95% CI, 1.00-1.02; P = 0.015), and higher enhanced liver fibrosis score (HR per unit, 1.26; 95% CI, 0.98-1.61; P = 0.073). Overall, rates of adverse events and laboratory abnormalities were similar between groups.

Conclusion: Treatment with the LOXL2 inhibitor simtuzumab for 96 weeks did not provide clinical benefit in patients with PSC.

 
Question posée
 
Sécurité et efficacité du simtuzumab, un ac monoclonal dirigé contre le Lysyl oxidase like-2 (LOXL2) qui joue un rôle central dans la fibrinogenèse et qui est augmenté dans le sérum et le foie des patients ayant une cholangite sclérosante primitive (CSP).
 
Question posée
 
Le simtuzumab est bien toléré mais il n’est pas plus efficace que le placebo.
 
Commentaires

Dommage pour cette approche originale! Toujours pas de nouvelle molécule pour le traitement des patients CSP.

 
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