Sa1041 Triple Therapy Under Real Life Conditions: Telaprevir (TVR) and Boceprevir (BOC) in Combination With Peginterferon-Alfa-2A Plus Ribavirin (P/R) in Treatment Experienced Patients Infected With Chronic Hepatitis C, Genotype 1. the PAN Study (original) (raw)
Related papers
2018
Objective: To analyze Rapid virological response (RVR) and End treatment response (ETR) in Hepatitis C genotype 3 infected patients being given Sofosbuvir and Ribavirin combination (dual) therapy presenting to Liver clinic of Benazir Bhutto Hospital. Methods: It was a retrospective study, conducted at Benazir Bhutto Hospital from January 2016 to July 2017. For this study, data of HCV subjects attending liver clinic (OPD) was obtained from computerized hospital management system (HMS). Variables that were obtained through administrative data included age, sex, pretreatment hemoglobin, TLC and platelet counts, pretreatment ALT, pretreatment PCR, and pretreatment ultrasound Liver findings. Only data of patients who fulfilled the inclusion criteria was included and data for patients who met the exclusion criteria was omitted. The inclusion criteria for patients was 18 years of age or older, having PCR for HCV RNA positive for genotype 3, treatment naïve, both cirrhotic and non-cirrhotic. The exclusion criteria included those that did not give informed consent, pregnant patients, history of active drug abuse, overt infection with other hepatitis viruses, autoimmune disease and HIV positive patients. Keeping the selection criteria in view total number of patients included in the study from liver clinic records was 135 and all had received Sofosbuvir with Ribavirin dual therapy in our OPDs for a duration of 24 weeks. 3 PCRs were performed during therapy for monitoring. One at the start of treatment, then at 4 weeks to assess RVR, then at the end of treatment at 24 weeks therapy to see ETR. Results: A total of 135 patients were included in the study having genotype 3 amongst which 33(24.4%) were males and 102(75.6%) were females. The mean age of participants was 46.23259 (± 11.86040) years. Of 135 patients, PCR of all 135 was available at four weeks of treatment and 112 (83%) had achieved RVR while PCR of 131 patients was available at completion of treatment i.e. at 24 weeks amongst whom 112(85.5%) had attained ETR. The association between attainment of RVR and attainment of ETR was also assessed using Pearson's Chi square test and results were statistically significant, showing that patients who achieved RVR were more likely to go on to achieve ETR. The comparison of patients who attained RVR with those who did not was also executed based on gender and Pearson's chi square test revealed no statistically significant difference in the two groups with p values greater than 0.05. Comparison of the mean age of patients who attained RVR with those who did not was made using independent t test and similarly comparison of mean pretreatment CBC indices, mean pretreatment ALT, mean pretreatment viral load was also done for the two groups i.e RVR achieved/not achieved using independent T test. The impact of advancing liver disease (as evidence by progressively worsening ultrasound liver findings) on 4 week viral clearance was assessed ising Mann Whitney test and none of these found any statistically significant association, with p values being greater than 0.05 in each case. Conclusion: In our study population, which was reflective of disease epidemiology in Rawalpindi, Pakistan: females were more affected than males, average age was 40 years and majority of patients presented early in the disease course with normal liver findings on ultrasound, followed by the non specific findings of fatty liver. Sofosbuvir plus Ribavirin combination therapy has shown to be very effective and successful in achievement of viral clearance with little or no resistance in genotype 3 infected patients in our study population regardless of the age, gender and other variable differences. 83% of the patients achieved RVR at completion of four weeks of treatment while 85.5% had attained ETR at end of therapy. Patients who achieved RVR were more likely to go on to achieve ETR.
Viral kinetic of HCV genotype-4 during pegylated interferon alpha 2a: ribavirin therapy
Journal of Viral Hepatitis, 2008
Summary. Kinetics of hepatitis C virus (HCV) during pegylated interferon (PEG-IFN) and early monitoring of viral decline were recently described to predict treatment outcomes and in turn reduce the course of treatment, adverse effects and cost. However, there is limited (if any) information on the viral dynamics of HCV-4. Our aim is to follow the HCV-RNA kinetics during PEG-IFN alpha 2a and ribavirin therapy and the best time for predicting sustained viral response (SVR) in genotype-4 patients. Serum HCV-RNA levels before initial dosing (baseline level) and at 24 h, week 1, week 4, week 12, week 24, week 48 and week 72 were assessed in 84 HCV genotype-4 patients treated weekly by PEG-IFN alpha 2a and daily ribavirin. At the end of treatment, out of the 84 treated patients, 19 (22.6%) were non-responders while 65 (77%) showed end-of-treatment response (ETR). However, 8 patients relapsed (9.5%), thus the SVR was observed in 57 patients (67.9%). Younger patients were more likely to attain SVR, where the odds of SVR increased by a factor of 0.94 for each year increase in age (95% CI: 0.90–0.99, P = 0.019). Although a significant negative correlation between stage of fibrosis and rate of viral decline at weeks 1 and 4 (P < 0.005 and 0.001, respectively) was seen, neither fibrosis stage (χ2 = 3.4882, P > 0.1) nor grade of inflammation (χ2 = 0.0057, P > 0.1) significantly predicted response to treatment. Non-responders had no or only a limited decline at week 1 and week 4, whereas sustained virological responders had a significant decline at both week 1 and week 4. Area under the (receiver operating characteristic) curve (AUC) revealed that week 12 is better than any other time point in predicting the SVR (AUC = 0.97; 95% CI: 0.94–1.01), (sensitivity 98.3%; 95% CI: 90.7–99.9), (specificity 88.5%; 95% CI: 71.0–96.0), positive predictive value of 94.9% and negative predictive value of 95.8%. A drop of more than 1.17 log viral load at week 1 and viral clearance or decline >3 log were considered as the earliest predictors of SVR. In genotype-4 patients, while failure to achieve an EVR at week 12 predicts non-response, an RVR at week1 and week 4 98% guaranteed SVR. These findings further re-enforce the value of week 12 in the course of IFN treatment. Genotype-4 patients who show significant viral clearance (>1.17log viral load) by the first week of treatment and viral clearance >3log by week 4 are expected to show SVR and should therefore be assigned to a shorter drug regimen lasting for 24 weeks. Those unfortunate cases who do not achieve viral clearance by week 1 or week 4 should not be deprived from the treatment but rather given more time till week 12 before being classified as non-responders.
New England Journal of Medicine
Background In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. Methods We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon-ribavirin and had a relapse, a partial response, or a null response. Patients were randomly assigned in a 3:1 ratio to receive coformulated ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir) and dasabuvir (250 mg twice daily) with ribavirin (1000 or 1200 mg daily) or matching placebos during the 12-week double-blind period. The primary end point was the rate of sustained virologic response 12 weeks after the end of study treatment. The primary efficacy analysis compared this rate among patients assigned to the active regimen with a historical response rate (65%) among previously treated patients with HCV genotype 1 infection and no cirrhosis who had received retreatment with telaprevir and peginterferon-ribavirin. Results A total of 394 patients received at least one study-drug dose. In the active-regimen group, 286 of 297 patients had a sustained virologic response at post-treatment week 12, for an overall rate of 96.3% (95% confidence interval, 94.2 to 98.4). This rate was noninferior and superior to the historical control rate. Rates were 95.3% among patients with a prior relapse (82 of 86 patients), 100% among patients with a prior partial response (65 of 65 patients), and 95.2% among patients with a prior null response (139 of 146 patients). Pruritus occurred more frequently with the active regimen (in 13.8% of patients) than with placebo (5.2%, P = 0.03). Three patients in the active-regimen group (1.0%) discontinued the study drugs owing to adverse events. Hemoglobin values of grade 2 (8.0 to <10.0 g per deciliter) and grade 3 (6.5 to <8.0 g per deciliter) occurred in 4.7% and 0.3% of patients in the active-regimen group, respectively. Conclusions Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response.
Antimicrobial Agents and Chemotherapy, 2014
combination with peginterferon alfa-2a-ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a-ribavirin in G1-infected prior peginterferon-ribavirin null responders. Null responders (<2-log 10 reduction in HCV RNA level at week 12) were given an open-label combination of 100 mg of ritonavir and 100 mg of DNV (100/100 mg DNVr) every 12 h (q12h) plus peginterferon alfa-2a-ribavirin for 12 weeks. All patients achieving an early virologic response (EVR; >2-log 10 decrease in HCV RNA by week 12) continued treatment with peginterferon alfa-2a-ribavirin; those without an EVR discontinued all study drugs. Twenty-four prior null responders were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) were infected with G1a. Ninety-six percent of patients had an IL28B non-CC genotype. A sustained virologic response at 24 weeks posttreatment (SVR24) was achieved in 67% of patients, with a higher rate in G1b-infected (88%) than G1a-infected (25%) patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated. Two patients withdrew prematurely from study medications due to adverse events. Two serious adverse events were reported; both occurred after completion of DNVr therapy and were considered unrelated to treatment. No grade 3 or 4 alanine aminotransferase (ALT) elevations were observed. DNVr plus peginterferon alfa-2a-ribavirin demonstrated high SVR24 rates in HCV G1b-infected prior null responders and was well tolerated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01185860.)
Hepatology, 2004
The aim of this study was to determine the efficacy of 14 weeks of treatment in patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early virological response (EVR). In a noncontrolled multicenter trial, 122 treatment-naive patients received 1.5 g/kg pegylated interferon alfa-2b subcutaneously once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks 4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary end point was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks. SVR was obtained in 85 (90%) of 95 patients in the 14-week treatment group and 15 of (56%) 27 in the 24-week treatment group. Altogether, SVR was obtained in 100 of 122 patients (82%; 95% CI, 75%-89%). SVR after 14 weeks of treatment was achieved more frequently among genotype 3a patients with low viral load compared with high viral load (98% vs. 79%; P ؍ .019). Logistic regression analysis showed that absence of bridging fibrosis/cirrhosis was the only independent predictor of SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR after 14 weeks of treatment. The results need to be confirmed in a randomized, controlled study before this treatment approach can be recommended, particularly for patients with genotype 3 and high viral load or severe fibrosis. (HEPATOLOGY 2004;40:1260 -1265
Virology: Research and Reviews, 2017
Background: Telaprevir with peginterferon/ribavirin (TVR/PR) leads to significantly higher sustained virological response (SVR) rates with partial response or relapse after prior treatment with peginterferon alpha (PegIFN)/ribavirin (RBV) in patients infected with hepatitis C. We studied the efficacy of TVR/PR in patients with prior treatment failure, including those with a null response (<2 Log10 decline in HCV RNA), to peginterferon/ribavirin). Objectives: It was aimed to evaluate efficacy, safety and side effects of the addition of telaprevir to a regimen of peg-interferon plus ribavirin in patients with chronic HCV genotype 1 infection who did not have a sustained virologic response to previous treatment. Method: This study is in a retrospective design with patients receiving TVR based triple therapy for chronic hepatitis C in a single center of a Middle Anatolia. The patient who did not have the response with the previous peg-interferon alpha with ribavirin treatment included the study. Virological response results were assessed at weeks 4, 12, and 24 during the triple treatment. If the HCV RNA levels was > 1000 IU/mL at week 4 or negative at week 4 but >1000 IU/mL at week 12, treatment was discontinued. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The adverse events were evaluated during the therapy. Results: Twenty-six patients infected with genotypes 1a or 1b hepatitis C virus were included the study. All of the patients had been previously treated with PegIFN plus RBV. Sustained virologic response occurred in 21 out of 22 previous relapse patients (95.5%) and 2 out of the 4 non-responder or partial responder patients (50%). The most common side effects were fatigue, insomnia, myalgia and anaemia. Conclusions: In conclusion, the response to TVR treatment rate was high in previous relapsers but it was low in non-responder or partial responder patients.
Infection, 2011
Background Pegylated interferon (PEG-IFN) and ribavirin is the most effective treatment for chronic hepatitis C virus (HCV) hepatitis, but the rate of sustained virological response (SVR) remains approximately 50%, and 15-20% of all treated patients have a virological relapse after completing the treatment. Studies on the SVR have failed to discriminate between non-responders and relapsers. Aims To identify the risk factors for relapse among patients with an end-of-treatment response (ETR). Methods We retrospectively analyzed 281 patients consecutively treated with PEG-IFN and ribavirin with a follow-up period of at least 24 weeks. The baseline details collected on each patient included demographic data, histological features, and biochemical profiles. Results Forty-six patients (16.4%) relapsed during the first 6 months of follow-up after discontinuing the therapy. Relapser patients were significantly older, had more steatosis, fibrosis, and showed significantly lower rapid virological response (RVR) rates compared with SVR patients. By logistic regression analysis, only the absence of RVR was found to be significantly associated with relapses in both subgroups of patients with genotypes 1 and 4 (p \ 0.004) and those with genotypes 2 and 3 (p \ 0.006). Severe fibrosis was also predictive of relapsing disease, but only for genotypes 2 and 3 patients (p \ 0.003). During the treatment, serum HCV-RNA decreased more rapidly in patients with SVR compared to non-responder and relapser patients (p \ 0.001). Interestingly, relapser patients exhibited an intermediate serum HCV-RNA decay during the first 4 weeks of therapy. Conclusion Among HCV patients treated with PEG-IFN and ribavirin, the absence of RVR was the most important independent predictor of relapse, independent of the HCV genotype. In the subgroup of genotypes 2 and 3 patients, the severity of fibrosis was also an important factor associated with the relapse rate.
Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin
2014
Background In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. Methods We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon-ribavirin and had a relapse, a partial response, or a null response. Patients were randomly assigned in a 3:1 ratio to receive coformulated ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir) and dasabuvir (250 mg twice daily) with ribavirin (1000 or 1200 mg daily) or matching placebos during the 12-week double-blind period. The primary end point was the rate of sustained virologic response 12 weeks after the end of study treatment. The primary efficacy analysis compared this rate among patients assigned to the active regimen with a historical response rate (65%) among previously treated patients with HCV genotype 1 infection and no cirrhosis who had received retreatment with telaprevir and peginterferon-ribavirin. Results A total of 394 patients received at least one study-drug dose. In the active-regimen group, 286 of 297 patients had a sustained virologic response at post-treatment week 12, for an overall rate of 96.3% (95% confidence interval, 94.2 to 98.4). This rate was noninferior and superior to the historical control rate. Rates were 95.3% among patients with a prior relapse (82 of 86 patients), 100% among patients with a prior partial response (65 of 65 patients), and 95.2% among patients with a prior null response (139 of 146 patients). Pruritus occurred more frequently with the active regimen (in 13.8% of patients) than with placebo (5.2%, P = 0.03). Three patients in the active-regimen group (1.0%) discontinued the study drugs owing to adverse events. Hemoglobin values of grade 2 (8.0 to <10.0 g per deciliter) and grade 3 (6.5 to <8.0 g per deciliter) occurred in 4.7% and 0.3% of patients in the active-regimen group, respectively. Conclusions Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response.
BMC Research Notes, 2011
Background Chronic hepatitis C (CHC) Patients, infected with genotype (GT) 2 or 3 are treated with Peg-IFN and ribavirin (RBV) (800 mg/day) for 24 weeks. Treatment duration can be shortened to 12-16 weeks if a higher dose of RBV (1.000/1.200 mg/day) was used without considerable loss of responsiveness or increased risk of relapse. Previously we have shown that in patients with CHC, GT 2/3 RBV can be reduced to 400 mg/day if administered for 24 weeks without an increase in relapse rates. Therefore we investigated the efficacy of a reduced RBV dosage of 400 mg/day with shorter treatment duration (16 weeks). Methods Treatment naïve patients with CHC, GT 2/3 were randomized to receive 180 μg peginterferonα2a/week in combination with either 800 (group C) or 400 mg/d (group D) for 16 weeks. The primary endpoint was SVR. Results 12 months after the first patient was randomized a inferior outcome of group D as compared to group C was noted, therefore the study was terminated. At study termination 89 patients were enrolled (group C: 31, D: 51). The SVR rate was statistically different in the two study groups with 51.6% in group C and 28.4% in group D (p = 0.038). Patients with low viral load had higher SVR rates (C: 67%, D: 33%) than those with high viral load (C: 33%, D: 21%). Conclusion Both treatment duration and the dose of RBV play a major role to optimize outcome of patients with GT3. If one intends to shorten the treatment weight based RBV dose should be used, if lower RBV doses are used patients should be treated for at least 24 weeks as. A treatment regimen with a reduced RBV dosage and shortened treatment duration is associated with low SVR rates due to high relapse rates. Trial registration NCT01258101