P1119 Early Viral Kinetics Do Not Predict Treatment Outcome With Sofosbuvir + Ribavirin for 12 or 24 Weeks in HCV Genotype 2/3 Patients in the Valence Trial

Zeuzem, Stefan; Dusheiko, GM; Colombo, Marta; Flisiak, Robert; Hyland, Robert H.; Illeperuma, Ari; Brainard, Diana M.; Symonds, William T.; McHutchison, John G.; Weiland, O; Reesink, H.W.; Brown, Abigail; Pol, Stanislas; Hézode, Christophe; Esteban, Rosa

doi:10.1016/s0168-8278(14)61279-4

Cited by 7 publications

(10 citation statements)

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“…Several analyses (available as abstracts [40][41][42][43][44] and a slide presentation [44]) examined factors predictive of response in patients with chronic hepatitis C receiving sofosbuvircontaining regimens in the trials discussed in Sects. 4.1 and 4.2.…”

Section: Predictors Of Responsementioning

confidence: 99%

“…at weeks 1, 2 and/or 4) had limited clinical utility for determining treatment futility [40]. Similarly, an analysis of the VALENCE trial found that on-treatment viral kinetics were not significantly predictive of response [41]. Another analysis reported that relapse after week 12 post-treatment occurred rarely with sofosbuvir-containing regimens in phase III trials, suggesting that SVR12 reliably predicts a durable treatment response [42].…”

Section: Predictors Of Responsementioning

confidence: 99%

“…4.1 and 4.2) and on-treatment viral kinetics were not predictive of eventual SVR (Sect. 4.3) [41]. Sofosbuvir generally has a low potential for drug interactions, although sofosbuvir concentrations may be reduced by the concomitant administration of potent intestinal P-gp inducers (Sect.…”

Section: Place Of Sofosbuvir In the Management Of Chronicmentioning

confidence: 99%

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Sofosbuvir: A Review of its Use in Patients with Chronic Hepatitis C

Keating¹

2014

Drugs

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Sofosbuvir (Sovaldi(®)) is a nucleotide hepatitis C virus (HCV) NS5B polymerase inhibitor that has pangenotypic antiviral activity and a high genetic barrier to resistance. This article reviews the clinical efficacy and tolerability of sofosbuvir in patients with chronic hepatitis C and summarizes its pharmacological properties. Interferon-free treatment with sofosbuvir plus ribavirin achieved high sustained virological response (SVR) rates in treatment-naïve and treatment-experienced patients with HCV genotype 2 or 3 infection, and also had efficacy in patients with HCV genotype 1 infection. Sofosbuvir plus ribavirin was also effective in patients co-infected with HCV and HIV, and sofosbuvir plus ribavirin administered prior to liver transplantation prevented recurrent HCV infection in the majority of patients who had HCV RNA levels below the limit of quantification at the time of transplantation. Sofosbuvir plus peginterferon-α-2a and ribavirin achieved high SVR rates in patients with HCV genotype 1 infection, and also appeared effective in patients with HCV genotype 4, 5 or 6 infection. Oral sofosbuvir was generally well tolerated in patients with chronic hepatitis C. The most commonly reported adverse events and laboratory abnormalities were consistent with those expected with ribavirin and peginterferon-α. In conclusion, sofosbuvir represents an important advance in the treatment of chronic hepatitis C.

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Section: Predictors Of Responsementioning

confidence: 99%

Section: Predictors Of Responsementioning

confidence: 99%

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Sofosbuvir: A Review of its Use in Patients with Chronic Hepatitis C

Keating¹

2014

Drugs

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“…With the advent of DAAs, the exceptionally high SVR rates achieved have made it far less important to predict response versus non-response and early viral kinetics (i.e. time to viral negativity) do not predict treatment failure [11, 12]. However, it would be extremely useful if early HCV kinetics could be used to determine duration of treatment needed to achieve cure, i.e.…”

Section: Introductionmentioning

confidence: 99%

HCV kinetic and modeling analyses indicate similar time to cure among sofosbuvir combination regimens with daclatasvir, simeprevir or ledipasvir

Dahari

Canini

Graw

et al. 2016

Journal of Hepatology

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Background&Aims Recent clinical trials of direct-acting-antiviral agents (DAAs) against hepatitis C virus (HCV) achieved >90% sustained-virological response (SVR) rates, suggesting that cure often took place before the end of treatment (EOT). We sought to evaluate retrospectively whether early response kinetics can provide the basis to individualize therapy to achieve optimal results while reducing duration and cost. Methods 58 chronic-HCV patients were treated with 12-week sofosbuvir+simeprevir(n=19), sofosbuvir+daclatasvir(n=19), or sofosbuvir+ledipasvir in three French referral centers. HCV was measured at baseline, day 2, every other week, EOT and 12 weeks post EOT. Mathematical modeling was used to predict the time to cure,i.e,<1 virus copy in the entire extracellular-body fluid. Results All but one patient who relapsed achieved SVR. Mean age was 60±11 years, 53% were male, 86% HCV genotype-1, 9% HIV coinfected, 43% advanced fibrosis (F3), and 57% had cirrhosis. At weeks 2, 4 and 6, 48%, 88% and 100% of patients had HCV<15 IU/ml, with 27%, 74% and 91% of observations having target-not-detected, respectively. Modeling results predicted that 32(43%), 16(23%), 7(13%), 5(9%) and 3(5%) subjects were predicted to reach cure within 6, 8, 10, 12 and 13 weeks of therapy, respectively. The modeling suggested that the patient who relapsed would have benefitted from an additional week of sofosbuvir+ledipasvir. Adjusting duration of treatment according to the modeling predicts reduced medication costs of 43%-45% and 17%-30% in subjects who had HCV<15 IU/ml at weeks 2 and 4, respectively. Conclusions The use of early viral-kinetic analysis has the potential to individualize duration of DAA therapy with a projected average cost-saving of 16%-20% per 100-treated persons.

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“…In the initial clinical trials with SOF, HCV RNA suppression by week 4 was nearly universal and was not associated with cure, including patients infected with HCV genotype-3 who are currently considered the most difficult to treat [7, 8]. Subsequent studies did not find an association between early viral kinetics and treatment outcomes [9, 10]. As a result, on treatment HCV RNA measurements (weeks 2 and/or 4) are currently recommended by both EASL (www.easl.eu) and the AASLD/IDSA (www.hcvguidelines.org) only as a means to monitor adherence and a fixed duration of DAA therapy has eclipsed the RGT approach.…”

mentioning

confidence: 99%