Keith Alcorn, Michael Carter
Published: 20 April 2012
A real-world study of new hepatitis C protease inhibitors in the group of patients who have been told they should not wait for newer, experimental antivirals has shown a much higher rate of serious adverse events and treatment discontinuations than in clinical trials, Dr Christophe Hézode reported on behalf of the French Compassionate Use of Protease Inhibitors in Cirrhotics cohort study at the 2012 International Liver Congress in Barcelona on Thursday.
However rates of virologic response after 16 weeks of treatment were high in this group of patients who had previously relapsed or failed to respond to pegylated interferon and ribavirin.
The programme and cohort study were established prior to the licensing of telaprevir (Incivo/Incivek) and boceprevir (Victrelis) in Europe in order to provide early access to the new drugs in patients with hepatitis C judged to be in urgent need of treatment. Under French law experimental drugs may be made available prior to licensing to patients with urgent clinical needs, if data on safety are collected.
The cohort study sought to evaluate outcomes in patients who received the drugs, and in particular to evaluate the tolerability and efficacy of the new drugs in patients with hepatitis C mono-infection and compensated cirrhosis with a previous history of non-response or relapse after standard treatment with pegylated interferon and ribavirin.
Early access was provided to telaprevir or boceprevir for 655 patients at 55 hospitals in France; 455 were eligible for inclusion in the cirrhosis analysis (296 telaprevir, 149 boceprevir).
The telaprevir regimen consisted.....
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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)
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
Christophe Hezode
Author:
C. Hezode1*, 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
C. Hezode1*, 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
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%) |
View Abstract- http://mobile.ilcapp.eu/EASL_161/poster_23756/program.aspx
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