Ribavirin In Treatment-naive Patients Research Articles

Virologic Response Rates of Weight-Based Taribavirin Versus Ribavirin in Treatment-Naive Patients with Genotype 1 Chronic Hepatitis C

Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C. The study aimed to determine if weight-based dosing of taribavirin (TBV), an oral prodrug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration. A U.S. phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naive patients infected with genotype 1 who were stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800-1400 mg/day) with pegylated interferon alfa-2b for 48 weeks. The SVR rates in this difficult-to-cure patient demographics (mean age, 49 years; 61% male; 30% African American or Latino; high viral load; advanced fibrosis; and mean weight, 82 kg) were 28.4%, 24.3%, 20.6%, and 21.4% in the 20, 25, and 30 mg/kg TBV groups and the RBV group, respectively. There were no statistical differences in the efficacy analyses. Anemia rates were significantly lower (P < 0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7%, respectively) compared to RBV (32.9%). The most common adverse events in all groups were fatigue, diarrhea, and insomnia. Diarrhea, reported in 38% of TBV patients versus 21% of RBV patients, was generally mild and not dose-limiting. All TBV doses demonstrated efficacy and tolerability comparable to that of RBV; however, the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy. Anemia rates were significantly lower for TBV given at 20-25 mg/kg than RBV. These data suggest weight-based dosing with TBV provides a safe and effective treatment alternative to RBV for chronic hepatitis C. American Association for the Study of Liver Diseases.

Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial

Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin. In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1.5 mug/kg plus ribavirin 800-1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400-1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00423670. Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44-64], p=0.013 for PRB28; 58/103 [56%, 44-66], p=0.005 for PR4/PRB24; 69/103 [67%, 57-76], p<0.0001 for PRB48; and 77/103 [75%, 65-83], p<0.0001 for PR4/PRB44; vs 39/104 [38%, 28-48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27 [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates of anaemia (227/416 [55%] vs 35/104 [34%]) and dysgeusia (111/416 [27%] vs nine of 104 [9%]) than did the control group. In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. Merck.

Meta-analysis Shows Extended Therapy Improves Response of Patients With Chronic Hepatitis C Virus Genotype 1 Infection

Clinical trials provided conflicting results about whether extended duration of treatment with pegylated interferon-alfa (pegIFN-alfa) and ribavirin (more than 48 weeks) improves rates of sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 and slow virologic response. We performed a meta-analysis to determine the overall impact of extended treatment, compared with standard treatment, on virologic response rates in these patients. We performed a literature search to identify randomized controlled trials (RCTs) that included monoinfected, treatment-naive patients infected with HCV genotype 1; data were compared between slow responding patients treated with pegIFN-alfa-2a/b plus ribavirin for 48 weeks and those that received extended treatment (as much as 72 weeks). End points included SVR rates, end-of-treatment (EOT) response and relapse rates; they were calculated according to the DerSimonian-Laird estimate. Six RCTs assessed the benefits of extended treatment with pegIFN-alfa-2a/b and ribavirin in treatment-naive patients with HCV genotype 1 that were slow responders (n = 669). The extended treatment significantly improved SVR rates in slow responders, compared with the standard of care (14.7% increase in overall SVR; 95% confidence interval, 4%-25.5%; P = .0072). Rates of viral relapse were significantly reduced by extended treatment, but EOT response rates were similar. The frequency of voluntary treatment discontinuation, but not of serious adverse events, was significantly increased by extended therapy. Extending the duration of treatment with pegIFN-alfa-2a/b and ribavirin in patients with HCV genotype 1 and a slow response to therapy improves the rate of SVR.

Dynamic Evolution of Therapy for Chronic Hepatitis C: How will Novel Agents be Incorporated into the Standard of Care?

There is a need for improved treatment strategies and new therapeutic agents to increase cure rates in chronic hepatitis C virus (HCV) infection. Ongoing trials are aimed at optimizing sustained virological response rates with pegylated interferon (PEG-IFN) plus ribavirin. For a new agent to supplant the standard of care it must augment the strengths or compensate for the weaknesses of PEG-IFN plus ribavirin. To improve cure rates on its own, a new agent must not only suppress replication of the virus, but also clear infected hepatocytes. It is now clear that new anti-HCV agents will be used, at least initially, against a backbone of PEG-IFN plus ribavirin. A broad spectrum of agents is under investigation and it is hoped that these drugs will ultimately increase cure rates, reduce the required duration of therapy, improve tolerability and possibly simplify therapy. Reductions in serum HCV RNA ranging from 2 to 5 log10 IU/ml have been obtained in human trials with NS3/4A protease inhibitors and polymerase inhibitors. A minimum of additive reductions in serum HCV RNA levels have been observed when agents in these classes have been administered with PEG-IFN plus ribavirin in treatment-naive patients. Preliminary results in non-responders to IFN are less promising. Combinations of small molecules will be needed in order to produce sustained suppression of HCV replication in the absence of the standard of care, and such large clinical trials are several years away. The treatment paradigm for chronic hepatitis C continues to evolve and will eventually incorporate new drugs as they are approved.

Pegylated IFN-α2b plus ribavirin for treatment-naive patients coinfected with HCV and HIV

Since 1995, after the generalization of highly active antiretroviral therapy (HAART), HCV coinfection in patients with HIV has become a clinical problem of first magnitude. In fact, currently, HCV coinfection is the primary cause of morbi–mortality of AIDS patients in many hospitals. As a consequence, a significant number of clinical trials have been carried out during the past 8–10 years on HCV/HIV-coinfected patients, and have been coincident that the use of pegylated interferon (PEG-IFN) plus ribavirin should be now the gold standard for treating these patients. Various prospective, randomized studies have reached the conclusion that PEG-IFN-α2b plus ribavirin achieves HCV cure rates in approximately 50% of all patients, together with important clinical consequences, since hepatic illness progression stops or even reverts. Although adverse events are extremely common with this combined treatment, it is also true that their handling by experts means that only 10–15% of patients must abandon treatment.

Etiologic treatment of hepatitis C virus-associated mixed cryoglobulinemia

The treatment of mixed cryoglobulinemia (MC) includes several drugs steroids, cyclosporins, colchicine, plasmapheresis but given the documented association between MC and hepatitis C virus (HCV), the treatment of choice seems to be antiviral therapy. Several authors have reported the efficacy of interferon (IFN) alpha in the inhibition of HCV replication and reduction of cryoglobulin levels. The therapy with IFN as monotherapy in MC shows a complete response rate in only 10 12% of cases. Complete response to therapy using a combination of IFN plus ribavirin varies in different studies from 18% to 64% of cases. There are only two studies on the treatment of MC with peginter- feron plus ribavirin. Both studies, given the high number of complete responders, reinforce the idea that peginterferon plus ribavirin is, at present, the best avaible treatment for cryoglobulinemic syndrome. The results obtained with peginterferon combined therapy are superior to standard interferon plus ribavirin in treatment-naive patients. In fact, a sustained virological response was observed in 44% of patients; the same results were obtained for clinical (purpura and arthralgia disappearance) and biochemical (aminotransaminases normalization) responses. New drug combinations, like peginterferons plus anti-CD20 antibodies, should be considered for treatment of MC in the future.

Daily consensus interferon versus peg-interferon alfa2b with weight based ribavirin in treatment-naive patients with chronic hepatitis C serotype-1

Daily consensus interferon versus peg-interferon alfa2b with weight based ribavirin in treatment-naive patients with chronic hepatitis C serotype-1

Daily dose of interferon alpha-2b and ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection: a randomised controlled study

The treatment of patients with hepatitis C virus (HCV) genotype 1 infection remains disappointing. In 1999, we started a multicentre study comparing two regimens of recombinant interferon (IFN) alpha-2b plus ribavirin. Group A (90 patients) received ribavirin plus IFN alpha-2b 5 MU/day for 1 month (induction therapy) followed by IFN alpha-2b 5 MU thrice weekly for 5 months. Group B (85 patients) received ribavirin plus IFN alpha-2b 5 MU thrice weekly for 6 months. Responders in both arms received IFN alpha-2b 3 MU thrice weekly for a further 6 months. A follow-up evaluation was performed at 18 months. One hundred and seventy-five consecutive treatment-naive patients with HCV genotype 1 infection were enrolled in the study. A sustained virological response (SVR) was obtained in 51 (29%) patients: 28 in group A (31%) and 23 in group B (27%). HCV-RNA clearance was greater at 3 months among patients who received induction therapy (57 vs 39%; p < 0.02). Age, sex, and initial viral load did not influence the achievement of a SVR. HCV clearance at the end of the study was lower in cirrhotic patients (3/26 vs 48/149; p < 0.05). The only SVR in patients with cirrhosis occurred in those from group A (p < 0.05). Both regimens were well tolerated. This study confirms the low rate of SVR in treatment-naive patients with HCV genotype 1 infection treated with IFN alpha-2b plus ribavirin. A 4-week induction regimen was slightly superior to standard IFN alpha-2b plus ribavirin. Although the number of patients with cirrhosis was low, induction therapy seemed to be more effective in cirrhotics. Given its safety and tolerability, the induction regimen evaluated here may be a therapeutic option in treatment-naive patients with HCV genotype 1 infection.

High dose daily interferon-alpha induction and secondary adjunction of ribavirin in treatment-naive patients with chronic hepatitis C: A multicentric, randomised, controlled trial

To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-alpha) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-alpha 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-alpha 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. Efficacy of IFN-alpha induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P=0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-alpha alone: 18/28 (64%) vs 10/26 (39%); P=0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P=0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P=0.99). A 4 week IFN-alpha induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-alpha for 6 months in HCV-RNA negative patients after 6 months of IFN-alpha significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.

619 Peginterferon α-2a (40 kDa) plus ribavirin in treatment-naive patients with chronic hepatitis C and genotype 2 or 3 infection: Individual estimated probability of sustained virological response

619 Peginterferon α-2a (40 kDa) plus ribavirin in treatment-naive patients with chronic hepatitis C and genotype 2 or 3 infection: Individual estimated probability of sustained virological response

Etanercept as an adjuvant to interferon and ribavirin in treatment-naive patients with chronic hepatitis C virus infection: a phase 2 randomized, double-blind, placebo-controlled study

Current therapies for patients with chronic hepatitis C virus (HCV) do not achieve sustained viral clearance in most patients, and are associated with severe toxic effects. Our aim was to investigate the efficacy and safety of etanercept as adjuvant to interferon and ribavirin in treatment-naive patients with HCV. Double-blind, randomized, placebo controlled trial. Fifty patients with chronic HCV were randomly assigned to receive interferon alfa-2b and ribavirin with either etanercept or placebo for 24 weeks. The main outcome measure was the absence of HCV RNA at 24 weeks, the on treatment response at the end of the etanercept randomization period. At 24 weeks, HCV RNA was absent in 63% (12/19) etanercept patients compared to 32% (8/25) placebo patients (P=0.04). In addition, patients receiving etanercept had lower frequency of most adverse events categories compared to placebo. Etanercept given for 24 weeks as adjuvant therapy to interferon and ribavirin significantly improved virologic response at the end of the etanercept randomization period among patients with HCV, and was associated with decreased incidence of most adverse effects associated with interferon and ribavirin.

Hepatitis C infection with normal transaminases: Is the treatment worse than the disease?

Hepatitis C infection with normal transaminases: Is the treatment worse than the disease?

986 Pre-treatment prediction of response to interferon by cDNA microarray with high accuracy validated by cross-over study

The treatment of mixed cryoglobulinemia (MC) includes several drugs steroids, cyclosporins, colchicine, plasmapheresis but given the documented association between MC and hepatitis C virus (HCV), the treatment of choice seems to be antiviral therapy. Several authors have reported the efficacy of interferon (IFN) alpha in the inhibition of HCV replication and reduction of cryoglobulin levels. The therapy with IFN as monotherapy in MC shows a complete response rate in only 10 12% of cases. Complete response to therapy using a combination of IFN plus ribavirin varies in different studies from 18% to 64% of cases. There are only two studies on the treatment of MC with peginter- feron plus ribavirin. Both studies, given the high number of complete responders, reinforce the idea that peginterferon plus ribavirin is, at present, the best avaible treatment for cryoglobulinemic syndrome. The results obtained with peginterferon combined therapy are superior to standard interferon plus ribavirin in treatment-naive patients. In fact, a sustained virological response was observed in 44% of patients; the same results were obtained for clinical (purpura and arthralgia disappearance) and biochemical (aminotransaminases normalization) responses. New drug combinations, like peginterferons plus anti-CD20 antibodies, should be considered for treatment of MC in the future.

304 Daily dosing regimen of consensus interferon and ribavirin for treatment-naive patients with chronic hepatitis C and genotype 1

304 Daily dosing regimen of consensus interferon and ribavirin for treatment-naive patients with chronic hepatitis C and genotype 1

High dose induction therapy with consensus interferon and ribavirin for treatment-naive patients with hepatitis C

High dose induction therapy with consensus interferon and ribavirin for treatment-naive patients with hepatitis C

Treatment of hepatitis C with interferon and ribavirin.

Hepatitis C is a worldwide problem that frequently results in end-stage liver disease and its complications. Treatment for hepatitis C virus (HCV) has been rather ineffective but several recent studies have clarified the role of interferon and ribavirin therapy. In line with therapeutic progress in HIV infection, hepatitis C is now entering the era of multidrug antiviral therapy. Ribavirin is an orally active synthetic guanosine analogue with theoretical antiviral and immunomodulatory actions. In this review we have evaluated the role of interferon and ribavirin in treatment-naive patients, relapsers and non-responders. In naive patients the combination results in improved end-of-treatment and sustained response rates, with an overall 41% sustained virological response rate in patients treated for 48 weeks. Therapeutic benefit also extends to the traditionally difficult to treat patients (genotype 1, high vital load and advanced fibrosis). The addition of ribavirin to interferon has also resulted in an increased toxicity profile, which has made therapy more difficult for both the patient and managing physician. However, the significant improvement in response rates for all patients makes combination therapy the most appropriate choice as the first-line therapy for suitable patients with chronic viral hepatitis C. Appropriate management with interferon and ribavirin includes assessing the patient's HCV genotype to determine the optimal duration of therapy, assessing therapeutic efficacy by measuring HCV-RNA at 24 weeks and monitoring for the additional ribavirin side-effects.

High-dose IFN-A induction followed by IFN plus ribavirin in treatment-naive patients with chronic hepatitis C: A prospective, randomized, controlled trial

High-dose IFN-A induction followed by IFN plus ribavirin in treatment-naive patients with chronic hepatitis C: A prospective, randomized, controlled trial