Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial

Abstract

Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.Trial RegistrationClinicalTrials.gov NCT00803309

Real‐world effectiveness of sofosbuvir‐based treatment regimens for chronic hepatitis C genotype 3 infection: Results from the multicenter German hepatitis C cohort (GECCO‐03)

“…SVR12 rates in this real world GECCO cohort were lower compared to phase III trials with comparable DAA regimes but much higher than those rates reported in the era of dual PEG/RBV‐based therapy in other real world cohorts …”

“…SVR12 rates in this real world GECCO cohort were lower compared to phase III trials with comparable DAA regimes but much higher than those rates reported in the era of dual PEG/RBV-based therapy in other real world cohorts. 17,18 SVR12 rates in non-cirrhotic patients who received a 12 week course of SOF/DCV ± RBV were higher as compared to SOF/RBV patients and only slightly lower as reported in the ALLY-3 trial. 13 Importantly, 12 weeks of SOF/DCV ± RBV were equally effective in treatment-experienced and −naïve patients, as reported before.…”

Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls

“…In this study, transient elastography (TE, Fibroscan ® ; Echosens, Paris, France) and Acoustic Radiation Force Impulse (ARFI) (Siemens Acuson S2000, Munich, Germany) elastography were used for assessment of liver fibrosis . In case of incongruent results in ARFI and TE or in cases of missing values of both, platelet counts, the AST/ALT ratio and the concentration of bilirubin and albumin were determined …”

“…21,22 In case of incongruent results in ARFI and TE or in cases of missing values of both, platelet counts, the AST/ALT ratio and the concentration of bilirubin and albumin were determined. 23 Measurements of ARFI and TE were performed at the same day after an overnight fast. For ARFI, only procedures with at least 10 valid acquisitions and a success rate of at least 60% were defined as eligible for the study.…”

Real World Experience with All-Oral Interferon Free Regimen for the Treatment of Lebanese Patients with Hepatitis C Virus (HCV) Infection

“…High rates of SVR12 were achieved even in patients, who were generally considered "difficult-totreat", such as patients with cirrhosis or those previously treated, and in HIV co-infected patients. Moreover, SVR12 rates in the real world GECCO cohort were lower compared to phase III trials with comparable DAA regimes, yet were much higher than rates reported in the era of dual PEG/RBV-based therapy real world cohorts (18)(19)(20).…”