Shobha Joshi

Retreating chronic hepatitis C with daily interferon alfacon‐1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results

Up to 50% of patients with chronic hepatitis C fail to respond to initial therapy with pegylated interferon (PEG‐IFN) and ribavirin (RBV). With unsuccessful viral eradication, these patients remain at risk for developing progression of their liver disease. Retreatment with PEG‐IFN/RBV yields sustained virologic response (SVR) rates that are under 10%. A wholly synthetic interferon, interferon alfacon‐1 or consensus interferon (CIFN) given with RBV, was evaluated in patients who failed initial PEG‐IFN/RBV therapy. The intent‐to‐treat analysis included 487 patients; 245 received CIFN 9 μg/day and RBV, and 242 received CIFN 15 μg/day and RBV. Within this group of patients, 59.3% had documented advanced fibrosis at baseline liver biopsy (stage F3 or F4). SVR rates were 6.9% (17/245 patients) in the 9 μg group and 10.7% (26/242) in the 15 μg group. In the intent‐to‐treat analysis, SVR rates were higher among patients with a >2‐log10 decrease in hepatitis C virus RNA during prior PEG‐IFN/RBV therapy: 11% (4/38) in the 9 μg group and 23% (7/31) in the 15 μg group. Among patients with lower baseline fibrosis scores (F0‐F3), SVR rates were 7.8% (15/192) in the 9 μg group and 13.1% (23/175) in the 15 μg group. In this same group of patients (F0‐F3), if a >2‐log10 decrease in hepatitis C virus RNA with previous PEG‐IFN/RBV treatment was achieved, SVR rates improved to 10.7% and 31.6% in the 9 μg and 15 μg groups, respectively. CIFN/RBV combination retreatment was safe and well tolerated. Conclusion: Retreatment of PEG‐IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG‐IFN/RBV, especially in interferon‐sensitive patients with lower baseline fibrosis scores. (HEPATOLOGY 2009.)

Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure

BACKGROUND & AIMS This is a phase II multicentre study to investigate the efficacy and safety of avatrombopag (E5501), an investigational second-generation thrombopoietin receptor agonist, administered one week prior to elective procedures in patients with thrombocytopenia secondary to cirrhosis. METHODS Adults with cirrhosis and platelet counts ⩾10 to ⩽58×10(9)/L were randomized to placebo or avatrombopag in two sequential cohorts. Cohort A: placebo vs. one of 3 different doses (100mg loading dose followed by 20, 40, or 80 mg/day on days 2-7) of a first-generation avatrombopag formulation. Cohort B: placebo vs. one of 2 different doses (80 mg loading dose followed by 10 mg/day for days 2-7, or 20mg/day for days 2-4) of a second-generation avatrombopag formulation. Primary end point was achievement of a platelet increase of ⩾20×10(9)/L from baseline and >50×10(9)/L at least once during days 4-8. RESULTS A total of 130 patients were randomized: 93 patients (51, cohort A; 42, cohort B) to avatrombopag and 37 (16, cohort A; 21 cohort B) to placebo. The primary end point was achieved by 49.0% of treated patients in cohort A and 47.6% in cohort B compared to 6.3% and 9.5% of controls; a dose response was seen. Each avatrombopag regimen had a higher proportion of responders compared with their respective cohort placebo arms (p<0.01), except for the 100/40 mg group in cohort A (p=0.17). The most common adverse events were nausea, fatigue, and headache. One patient in the (100/80) avatrombopag group, without a Doppler assessment at screening was diagnosed with portal vein thrombosis during post-treatment follow-up. CONCLUSIONS In this study avatrombopag was generally well-tolerated and increased platelet counts in patients with cirrhosis undergoing elective invasive procedures.