April 20, 2012

EASL 2012: Safety OF TELAPREVIR or Boceprevir IN COMBINATION WITH Peginterferon alfa/Ribavirin, in CIRRHOTIC NON RESPONDERS.

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Abstract

Title
Safety OF TELAPREVIR or Boceprevir IN COMBINATION WITH Peginterferon alfa/Ribavirin, in CIRRHOTIC NON RESPONDERS. FIRST RESULTS OF THE FRENCH EARLY ACCESS PROGRAM (ANRS CO20-CUPIC)

Speaker:
Christophe Hezode

Author:
C. Hezode
1*, C. Dorival2, F. Zoulim3, T. Poynard4, P. Mathurin5, S. Pol6, D. Larrey7, P. Cacoub4, V. de Ledinghen8, M. Bourlière9, P.H. Bernard10, G. Riachi11, L. Alric12, D. Samuel13, Y. Barthe2, H. Fontaine6, F. Carrat2, J.-P. Bronowicki14, ANRS CO20 CUPIC study group

Affiliation:
1Hôpital Henri Mondor, Inserm U955, Université Paris-Est, Creteil, 2Hôpital Saint-Antoine, Inserm U707, UPMC-Paris6, Paris, 3Hospices Civils de Lyon, Lyon, 4Hôpital de la Pitié-Salpêtrière, Paris, 5Hôpital Claude Huriez, Lille, 6Hôpital Cochin, Inserm U1016, Université Paris Descartes, Paris, 7Hôpital Saint-Eloi, Montpellier, 8Hôpital Haut-Lévèque, Pessac, 9Fondation Hôpital Saint Joseph, Marseille, 10Hôpital Saint André, Bordeaux, 11Hôpital Charles Nicolle, Rouen, 12Hôpital Purpan, Toulouse, 13Hôpital Paul Brousse, Villejuif, 14Hôpital de Brabois, Nancy, France. *christophe.hezode@hmn.aphp.fr

Phase III trials have shown that Telaprevir (TVR) is associated with frequent dermatological disorders and anemia, whereas Boceprevir (BOC) is associated with frequent anemia. However, few cirrhotic patients were included in these trials. We report the safety profiles of TVR or BOC in combination with peginterferon (PEG-IFN) and ribavirin (RBV) in the French Early Access Program for the use of protease inhibitors (PI).

Methods: Patients with compensated child A cirrhosis, HCV genotype 1 infection and prior relapse or partial response to PEG-IFN/RBV regimen were prospectively included to receive either 12 weeks of TVR, PEG-IFN-alfa2a/RBV and 36 weeks of PEG-IFN-alfa2a/RBV, or 4 weeks of PEG-IFN-2b/RBV and 44 weeks of BOC, PEG-IFN-2b/RBV without randomization which precludes any comparison between the two molecules. Safety analysis is restricted to patients with at least 8 weeks of treatment.

Results: Female-to-male ratio was 0.4 and mean age was 57 years in each group. Safety profiles are summarized in the table.

Conclusions: The safety profile of TVR or BOC with PEG-IFN/RBV in cirrhotic patients was poor and associated with increased SAE rates (30% to 51%) compared to those reported in phase III trials (9% to 14%). These data strongly suggest that triple therapy must be administered cautiously with intensive safety monitoring in these patients.

  TVR n=169 BOC n=138
Median treatment / PI duration (days) 112.0 / 85.0 113.0 / 84.0
Serious adverse events (SAE) / Discontinuation(AE) 87 (51%) / 20 (12%) 41 (30%) / 10 (7%)
Death 3 (2%) 1 (1%)
Anemia Grade 2(8.0-<10.0g/dL) / Grade 3-4(<8.0g/dL) 54 (32%) / 23 (14%) 39 (28%) / 8 (6%)
EPO use / Blood transfusion 94 (56%) / 32 (19%) 71 (51%) / 8 (6%)
Neutropenia Grade3-4(<1000/mm3) / G-CSF use 21 (12%) / 5 (3%) 14 (10%) / 7 (5%)
Thrombopenia Grade 3-4(<50000/mm3) / Thrombopoietin use 37 (22%) / 1 (1%) 10 (7%) / 1 (1%)
Rash Grade 3 / SCAR 11 (7%) / 0 (0%) 1 (1%) / 0 (0%)
Grade 3-4 infection / other AEs 4 (2%) / 90 (53%) 1 (1%) / 44 (32%)
[safety profile]

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