On-treatment HCV RNA as a predictor of sustained virological response in HCV genotype 3-infected patients treated with daclatasvir and sofosbuvir.

BACKGROUND AND AIMS: Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3-infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome. METHODS: In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome. RESULTS: Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA. CONCLUSIONS: On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen.

Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST-2).

UNLABELLED: Hepatitis C virus (HCV)-infected patients with cirrhosis are historically a difficult-to-treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1-infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open-label, single-arm study (OPTIMIST-2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1-infected treatment-naive or treatment-experienced patients with cirrhosis. Patients (aged 18-70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient-reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%-91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment-naive and treatment-experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient-reported outcomes improved from baseline to follow-up week 12. CONCLUSION: Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment-naive and treatment-experienced HCV GT1-infected patients with cirrhosis and was generally safe and well tolerated. (Hepatology 2016;64:360-369).

Patient satisfaction with alosetron for the treatment of women with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: The efficacy and tolerability of alosetron in women with diarrhea-predominant irritable bowel syndrome (IBS) have been established in double-blind, placebo-controlled trials. However, the degree to which alosetron fulfills the needs of those suffering from IBS has not been thoroughly examined from the patient's perspective. This randomized, double-blind, placebo-controlled study conducted in women with diarrhea-predominant IBS evaluated patients' overall satisfaction with treatment as well as their satisfaction with respect to several specific medication attributes. METHODS: Patients randomized to receive either alosetron 1 mg b.id. (n = 532) or placebo (n = 269) were administered a questionnaire on which they rated on 7-point Likert scales their prestudy IBS treatment (at the screening visit) or study medication (on wk 12 or final study visit) with respect to overall satisfaction and 11 specific medication attributes. RESULTS: Whereas approximately 10% of patients were satisfied or very satisfied overall with prestudy IBS medication, 69% of patients were satisfied or very satisfied overall with alosetron and 46% with placebo (p < 0.001) at the end of 12 wk of therapy. The majority of alosetron-treated patients (61-87%) were satisfied or very satisfied with each of 11 specific medication attributes (p < 0.001 vs placebo for each attribute). Favorable satisfaction ratings for alosetron were assigned to the five medication attributes that patients considered to be most important, including relief of urgency (68% alosetron vs 41% placebo), speed of relief (71% vs 40%), time to return to normal activities (75% vs 49%), relief of abdominal pain (62% vs 44%), and prevention of return of urgency (68% vs 42%). CONCLUSIONS: Women with diarrhea-predominant IBS are satisfied with alosetron 1 mg b.i.d. treatment overall and also with respect to specific attributes of IBS medication they consider most important.