A therapeutic dose and its pharmacokinetics of ropeginterferon Alfa-2b for hepatitis C treatment.

AIM: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. Its biweekly dosing schema has demonstrated tolerability and clinical efficacy for treating chronic hepatitis in previous clinical studies. This trial evaluates the pharmacokinetics of 400 µg ropeginterferon alfa-2b in patients with chronic hepatitis C virus (HCV) and provides the data to support the clinical utility of ropeginterferon alfa-2b at 400 µg. METHODS: Seventeen patients with chronic HCV genotype 2 were enrolled to receive a single injection of 400 µg ropeginterferon alfa-2b plus 14-day treatment of ribavirin. Pharmacokinetics, safety, and HCV RNA reduction/clearance were assessed. RESULTS: Tmax was 154.003 h and T1/2 was 114.273 h. The Cmax was 29.823 ng mL-1. AUClast was 9364.292 h∗ng mL-1 and AUCinf was 11084.317 h∗ng mL-1. All adverse events were mild or moderate, and there were no serious adverse events. A 1000-fold reduction in the geometric mean of HCV RNA was observed 14 d after the single injection of ropeginterferon alfa-2b. Two patients achieved clearance of HCV RNA, and the other five patients had HCV RNA levels lower than 200 IU mL-1. CONCLUSION: Ropeginterferon alfa-2b at 400 µg led to PK exposures associated with safety and notable clinical activity in patients with chronic HCV. This study suggests that ropeginterferon alfa-2b at 400 µg is an acceptable dosing regimen for treating chronic HCV and also provides supporting data for the clinical use of ropeginterferon alfa-2b at a higher starting dose for other indications.

Controlled Dietary Restriction With a Prepackaged Low-Residue Diet Before Colonoscopy Offers Better-Quality Bowel Cleansing and Allows the Use of a Smaller Volume of Purgatives: A Randomized Multicenter Trial.

BACKGROUND: Bowel preparation is burdensome, and less-demanding preparation procedures are needed. Few studies have investigated the effects of low-residue diet and prepackaged low-residue diet in combination with low-volume polyethylene glycol-electrolyte lavage solution during colonoscopy preparation. OBJECTIVE: We compared self-prepared low-residue diets with prepackaged low-residue diets in combination with low-volume polyethylene glycol. DESIGN: This was a single-blinded, 3-arm, multicenter, randomized controlled trial. SETTING: Colonoscopies were conducted in outpatient settings at 3 centers in Taiwan. PATIENTS: The study included 180 patients (age range, 20-75 years) who were scheduled for colonoscopy. INTERVENTIONS: Three groups were compared: group A included self-prepared, 1-day, low-residue diets with a same-day 2.0-L single-dose of polyethylene glycol; group B included prepackaged low-residue diets plus 2.0 L of polyethylene glycol; and group C included prepackaged low-residue diets plus 1.5 L of polyethylene glycol. MAIN OUTCOME MEASURES: The outcome measures were adherence, bowel-cleansing level, and patient satisfaction. RESULTS: One third of the subjects in group A, but none in the prepackaged low-residue diets groups, violated the dietary restrictions. The proportion of right-segment preparation failure was 15.0%, 1.7%, and 6.7% (p = 0.025). Accordingly, treatment B was superior to A (p = 0.008). Among subjects violating the low-residue diets guideline, the right-segment preparation failure rate was 25%. According to a multivariate analysis, low-residue diet compliance (adjusted OR = 6.55 (95% CI, 1.83-23.43)) and BMI were predictors of right-sided preparation adequacy, but the volume of polyethylene glycol ingested was not a predictor. Compared with group A, a greater proportion of subjects in groups B and C reported satisfaction. LIMITATIONS: Patients with high BMI and severe constipation were excluded from this study. This study included only an Asian population. CONCLUSIONS: The prepackaged low-residue diet provides excellent adherence, better bowel cleansing, and a better experience than a self-prepared low-residue diet. With good dietary compliance, 1.5 L of polyethylene glycol provides effective preparation.

Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

Peginterferon alfa-2a is associated with elevations in alanine aminotransferase at the end of treatment in chronic hepatitis C patients with sustained virologic response.

BACKGROUND: The purpose of this study was to investigate the incidence and demographic/clinical factors of alanine aminotransferase (ALT) abnormalities at the end of treatment (EOT) in chronic hepatitis C (CHC) patients with sustained virologic response (SVR). METHODS AND FINDINGS: Seven hundred naïve CHC patients who underwent combination treatment between January 2003 and December 2010 were included in the study. The patients with SVR and serum ALT>upper limit of normal (ULN) at the EOT were further analyzed. The effects of clinical characteristics, treatment regimen, and virologic variables were evaluated by logistic regression. Of the 700 included patients, 488 (69.7%) achieved an SVR after treatment, and 235 (33.6%) had serum ALT levels>ULN at the EOT. Of those 488 patients, 137 (28.1%) had abnormal ALT values at the EOT. A multivariate analysis showed that the occurrence of ALT abnormalities at the EOT was significantly associated with pegylated interferon (PEG-IFN) alfa-2a (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.45-3.45; P<0.001), baseline fatty liver (OR, 1.76; 95% CI, 1.16-2.76; P = 0.007), and baseline liver cirrhosis (OR, 2.35; 95% CI, 1.35-4.09; P = 0.002). CONCLUSIONS: Use of PEG-IFN-alfa-2a, fatty liver, and cirrhosis are important factors associated with EOT-ALT abnormality in CHC patients receiving combination therapy that achieve an SVR. PEG-IFN-alfa-2a-related EOT-ALT elevation will become normal at the end of follow-up, but fatty liver and cirrhosis-related ALT elevation will not be resolved.

A double-blind randomized controlled study to evaluate the efficacy of low-dose oral interferon-alpha in preventing hepatitis C relapse.

Low-dose oral interferon could exert immune-modulating effects in human. We conducted a clinical trial to investigate the efficacy of oral interferon-alpha in preventing hepatitis C relapse. Totally 169 genotype 1b chronic hepatitis C patients having achieved end-of-therapy virological clearance were randomized to receive interferon-alpha lozenge 500 IU/day (n=59), 1,500 IU/day (n=53), or placebo (n=57) for 24 weeks. Overall, no significant differences were found for the relapse rates in the 3 groups (P>0.05). However, in patients with fibroindex 1.4-1.7, relapse occurred in 1/12 (8.3%) 500 IU-group patients versus 9/21 (42.9%) patients of the other groups (P=0.05). In 158 patients receiving at least 4 weeks of oral interferon, significantly higher platelet count was found at the end of trial in the 500 IU group (P=0.003). In thrombocytopenic patients, a significantly expedited recovery of platelet count was found in the 500 IU group (P=0.002). No drug-related severe adverse events were reported. In conclusion, at 500 IU/day, oral interferon exerted a borderline suppression effect of virological relapse in chronic hepatitis C patients with mild liver fibrosis. Additionally, it significantly expedited platelet count recovery after the end of peginterferon therapy.