- Email: [email protected]
P1143 APPLICABILITY OF TRIPLE THERAPY IN CIRRHOTIC POPULATION: VALIDATION OF CUPIC DATA
POSTERS Virological response
Week 4 Week 8 Week 12 EoT SVR
Prior relapsers
Prior partial responders
Prior null responders
Undefined prior nonresponders
Undefined treatmentexperienced
6.7 (4/60) 53.1 (26/49) 72.4 (42/58) 69.7 (53/76) 63.2 (48/76)
0 66.7 50.0 52.9 35.3
0 0 16.7 (1/6) 28.6 (2/7) 14.3 (1/7)
0 36.0 (9/25) 59.4 (19/32) 41.7 (15/36) 38.9 (14/36)
12.5 (1/8) 60.0 (3/5) 75.0 (6/8) 72.7 (8/11) 54.5 (6/11)
(8/12) (7/14) (9/17) (6/17)
Percentages are based on available HCV RNA data. EoT, end of treatment; LLOD, lower limit of detection (not detectable or <40 IU/mL; SVR, sustained virological response.
Conclusions: In a real-life setting, BOC plus PegIFN/RBV led to SVR rates comparable with results from pivotal trials in prior nonresponders and relapsers with G1 infection. However, response rates were still suboptimal in null responders. P1142 META-ANALYSIS: ROLE OF INSULIN SENSITIZERS ADDED TO PEGINTERFERON AND RIBAVIRIN IN THE TREATMENT OF CHRONIC HEPATITIS C 1 1 J. Ampuero1 , R.K. Reddy2 , M. Romero-Gomez ´ . Unit for Clinical Management of Digestive Diseases, Valme University Hospital, Sevilla, Spain; 2 Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States E-mail: [email protected] Background and Aims: Insulin resistance has been found to be crucial in hepatitis C (HCV), being associated with poorer sustained virological response (SVR) rates. Therefore, our aim was to assess the impact of insulin sensitizers (metformin and pioglitazone) on SVR in HCV. Methods: We reviewed and identified studies in Pubmed and EMBASE to November 2013. According to inclusion (randomized clinical trials in patients with HOMA-IR >2) and exclusion criteria (Jadad scale <3), we selected 6 studies: three studies used metformin (n = 291 patients) and three pioglitazone (n = 287 patients). Five studies were in HCV genotype 1 and in genotype 4 (in pioglitazone group), all patients were treated with peginterferon and ribavirin during 48 weeks. The random effect models of Der Simonian and Laird method were used for heterogeneous studies using the Meta-Disc software 1.4 (Madrid, Spain). Results: Metformin studies used 500 mg/8 h (n = 2) or 850 mg/8 h (n = 1), while all pioglitazone studies used 30 mg/day. Patients taking metformin showed higher SVR rates (57.4%; 78/136 versus 41.3%; 64/155) (OR 1.93, 95% CI 1.21–3.10). The main adverse effect was diarrhea. On the other hand, pioglitazone did not influence SVR rate (40%; 58/145 versus 39.4%; 56/142) (OR 1.10, 95% CI 0.42–2.89). HOMA-IR decreased 1.81±0.13 in metformin group and 1.64±0.5 in pioglitazone group (p = 0.69).
P1143 APPLICABILITY OF TRIPLE THERAPY IN CIRRHOTIC POPULATION: VALIDATION OF CUPIC DATA C. Vinaixa1,2 , C. Satorres1 , M. Garcia1,2 , S. Benlloch1,2 , V. Aguilera1,2 , A. Rubin1,2 , M. Prieto1,2 , M. Berenguer1,2 . 1 Hepatology and Liver Transplantation, Hospital La Fe, 2 Ciber de Enfermedades Hepaticas y Digestivas (Ciberehd), Valencia, Spain E-mail: [email protected] Background and Aims: Anti-HCV triple therapy in cirrhotic patients is associated with severe adverse events (AE) and with lower efficacy results. Low platelet count (<100,000/mm3 ) in combination with low albuminemia (<3.5 g/dl) has been proposed as a threshold to use this treatment. We aimed to confirm whether this threshold applies in our cirrhotic treated population. Methods: All cirrhotic patients treated at our institution with triple therapy were included (n = 94). Of these, 52 had reached end-oftreatment, and 34 12th week post-treatment at time of analysis. Severe complications were defined as the development of an AE requiring drug discontinuation and/or death. Results: Baseline features were: 70% men, mean age 55 yrs, 75% genotype 1b, 21% diabetics, 7.5% HIV coinfected, high baseline HCV load (70%) and treatment experienced (70%, 53% of whom were null or partial responders), IL28B C/C: 83%. Liver function was preserved in the majority (92% Child ≤B7, 97% MELD ≤13). Telaprevir (TVR) was used in 63%, and lead-in was performed in 51% of cases. With regard to previously described risk factors, 46% had platelet count ≤100,000/mm3 , and 20% albuminemia <3.5 g/dl, with 14% harboring the 2 risk factors. Our results confirm the CUPIC data both in the 52 patients who had reached end-of-treatment, and in the 34 with follow-up up to 12 weeks post-treatment (table). In particular, severe complications were observed in 33% of the high risk group as compared to 19% of the low risk group, with sustained viral response reached by 20% and 71% of the groups, respectively. Table: Groups of risk
Albumin <3.5 g/dl Serious AE (%) ETR (%) SVR12 (%) Albumin ≥3.5 g/dl Serious AE (%) ETR (%) SVR12 (%)
Platelets ≤100,000/mm3
Platelets >100,000/mm3
33% (2/6) 50% (3/6) 20% (1/5)
50% (1/2) 50% (1/2) 100% (1/1)
12% (2/17) 61% (11/18) 55% (6/11)
19% (5/26) 77% (20/26) 71% (12/17)
Conclusions: Based on our findings in cirrhotic patients treated with triple therapy that confirm prior observations from CUPIC study, we do not recommend the use of triple therapy in the high risk group of patients with low platelet and albumin levels. P1144 DETERMINING THE COMPARATIVE EFFECTIVENESS OF EMERGING TREATMENT REGIMENS FOR HEPATITIS C VIRUS (HCV) INFECTION FROM SINGLE ARM PHASE III TRIALS M. Quintana1 , K. Broglio1 , E.S. Daar2 , Y. Yuan3 , A. Kalsekar3 , M.A. Detry1 , R.J. Lewis1,2 , T. Le3 , S.M. Berry1 . 1 Berry Consultants, LLC, Austin, TX, 2 Los Angeles Biomedical Research Institute, Los Angeles, CA, 3 Bristol-Myers Squibb, Princeton, NJ, United States E-mail: [email protected]
Conclusions: Metformin, but not pioglitazone, was able to increase between 1.2 and 3.1 times the likelihood to reach SVR in HCV genotype 1 patients with HOMA-IR >2 treated with peginterferon and ribavirin without serious adverse effects. No association was seen between improvement on insulin resistance and sustained virological response.
Background and Aims: The goal of this study is to use metaanalysis methods to determine SVR24 rate benchmarks required for a new HCV regimen to declare superiority over standard of care (SOC) in the setting of single arm trials where there is no network of treatment arms that can bridge between the new regimen and SOC. Methods: We conducted a literature search for studies of standard dose peginterferon-alfa plus ribavirin (IFNa+R) as well as telaprevir
Journal of Hepatology 2014 vol. 60 | S361–S522
S463
Week 4 Week 8 Week 12 EoT SVR
Prior relapsers
Prior partial responders
Prior null responders
Undefined prior nonresponders
Undefined treatmentexperienced
6.7 (4/60) 53.1 (26/49) 72.4 (42/58) 69.7 (53/76) 63.2 (48/76)
0 66.7 50.0 52.9 35.3
0 0 16.7 (1/6) 28.6 (2/7) 14.3 (1/7)
0 36.0 (9/25) 59.4 (19/32) 41.7 (15/36) 38.9 (14/36)
12.5 (1/8) 60.0 (3/5) 75.0 (6/8) 72.7 (8/11) 54.5 (6/11)
(8/12) (7/14) (9/17) (6/17)
Percentages are based on available HCV RNA data. EoT, end of treatment; LLOD, lower limit of detection (not detectable or <40 IU/mL; SVR, sustained virological response.
Conclusions: In a real-life setting, BOC plus PegIFN/RBV led to SVR rates comparable with results from pivotal trials in prior nonresponders and relapsers with G1 infection. However, response rates were still suboptimal in null responders. P1142 META-ANALYSIS: ROLE OF INSULIN SENSITIZERS ADDED TO PEGINTERFERON AND RIBAVIRIN IN THE TREATMENT OF CHRONIC HEPATITIS C 1 1 J. Ampuero1 , R.K. Reddy2 , M. Romero-Gomez ´ . Unit for Clinical Management of Digestive Diseases, Valme University Hospital, Sevilla, Spain; 2 Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States E-mail: [email protected] Background and Aims: Insulin resistance has been found to be crucial in hepatitis C (HCV), being associated with poorer sustained virological response (SVR) rates. Therefore, our aim was to assess the impact of insulin sensitizers (metformin and pioglitazone) on SVR in HCV. Methods: We reviewed and identified studies in Pubmed and EMBASE to November 2013. According to inclusion (randomized clinical trials in patients with HOMA-IR >2) and exclusion criteria (Jadad scale <3), we selected 6 studies: three studies used metformin (n = 291 patients) and three pioglitazone (n = 287 patients). Five studies were in HCV genotype 1 and in genotype 4 (in pioglitazone group), all patients were treated with peginterferon and ribavirin during 48 weeks. The random effect models of Der Simonian and Laird method were used for heterogeneous studies using the Meta-Disc software 1.4 (Madrid, Spain). Results: Metformin studies used 500 mg/8 h (n = 2) or 850 mg/8 h (n = 1), while all pioglitazone studies used 30 mg/day. Patients taking metformin showed higher SVR rates (57.4%; 78/136 versus 41.3%; 64/155) (OR 1.93, 95% CI 1.21–3.10). The main adverse effect was diarrhea. On the other hand, pioglitazone did not influence SVR rate (40%; 58/145 versus 39.4%; 56/142) (OR 1.10, 95% CI 0.42–2.89). HOMA-IR decreased 1.81±0.13 in metformin group and 1.64±0.5 in pioglitazone group (p = 0.69).
P1143 APPLICABILITY OF TRIPLE THERAPY IN CIRRHOTIC POPULATION: VALIDATION OF CUPIC DATA C. Vinaixa1,2 , C. Satorres1 , M. Garcia1,2 , S. Benlloch1,2 , V. Aguilera1,2 , A. Rubin1,2 , M. Prieto1,2 , M. Berenguer1,2 . 1 Hepatology and Liver Transplantation, Hospital La Fe, 2 Ciber de Enfermedades Hepaticas y Digestivas (Ciberehd), Valencia, Spain E-mail: [email protected] Background and Aims: Anti-HCV triple therapy in cirrhotic patients is associated with severe adverse events (AE) and with lower efficacy results. Low platelet count (<100,000/mm3 ) in combination with low albuminemia (<3.5 g/dl) has been proposed as a threshold to use this treatment. We aimed to confirm whether this threshold applies in our cirrhotic treated population. Methods: All cirrhotic patients treated at our institution with triple therapy were included (n = 94). Of these, 52 had reached end-oftreatment, and 34 12th week post-treatment at time of analysis. Severe complications were defined as the development of an AE requiring drug discontinuation and/or death. Results: Baseline features were: 70% men, mean age 55 yrs, 75% genotype 1b, 21% diabetics, 7.5% HIV coinfected, high baseline HCV load (70%) and treatment experienced (70%, 53% of whom were null or partial responders), IL28B C/C: 83%. Liver function was preserved in the majority (92% Child ≤B7, 97% MELD ≤13). Telaprevir (TVR) was used in 63%, and lead-in was performed in 51% of cases. With regard to previously described risk factors, 46% had platelet count ≤100,000/mm3 , and 20% albuminemia <3.5 g/dl, with 14% harboring the 2 risk factors. Our results confirm the CUPIC data both in the 52 patients who had reached end-of-treatment, and in the 34 with follow-up up to 12 weeks post-treatment (table). In particular, severe complications were observed in 33% of the high risk group as compared to 19% of the low risk group, with sustained viral response reached by 20% and 71% of the groups, respectively. Table: Groups of risk
Albumin <3.5 g/dl Serious AE (%) ETR (%) SVR12 (%) Albumin ≥3.5 g/dl Serious AE (%) ETR (%) SVR12 (%)
Platelets ≤100,000/mm3
Platelets >100,000/mm3
33% (2/6) 50% (3/6) 20% (1/5)
50% (1/2) 50% (1/2) 100% (1/1)
12% (2/17) 61% (11/18) 55% (6/11)
19% (5/26) 77% (20/26) 71% (12/17)
Conclusions: Based on our findings in cirrhotic patients treated with triple therapy that confirm prior observations from CUPIC study, we do not recommend the use of triple therapy in the high risk group of patients with low platelet and albumin levels. P1144 DETERMINING THE COMPARATIVE EFFECTIVENESS OF EMERGING TREATMENT REGIMENS FOR HEPATITIS C VIRUS (HCV) INFECTION FROM SINGLE ARM PHASE III TRIALS M. Quintana1 , K. Broglio1 , E.S. Daar2 , Y. Yuan3 , A. Kalsekar3 , M.A. Detry1 , R.J. Lewis1,2 , T. Le3 , S.M. Berry1 . 1 Berry Consultants, LLC, Austin, TX, 2 Los Angeles Biomedical Research Institute, Los Angeles, CA, 3 Bristol-Myers Squibb, Princeton, NJ, United States E-mail: [email protected]
Conclusions: Metformin, but not pioglitazone, was able to increase between 1.2 and 3.1 times the likelihood to reach SVR in HCV genotype 1 patients with HOMA-IR >2 treated with peginterferon and ribavirin without serious adverse effects. No association was seen between improvement on insulin resistance and sustained virological response.
Background and Aims: The goal of this study is to use metaanalysis methods to determine SVR24 rate benchmarks required for a new HCV regimen to declare superiority over standard of care (SOC) in the setting of single arm trials where there is no network of treatment arms that can bridge between the new regimen and SOC. Methods: We conducted a literature search for studies of standard dose peginterferon-alfa plus ribavirin (IFNa+R) as well as telaprevir
Journal of Hepatology 2014 vol. 60 | S361–S522
S463