By Brian Hoyle
WASHINGTON, DC -- November 6, 2013 -- Altered glucose metabolism, diabetes, and metabolic syndrome have been linked with a markedly diminished sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infections being treated with telaprevir-based triple therapy, according to results of an observational study presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
“Astonishingly, metabolic markers had a marked influence on SVR rates in this real-world setting, which was not reported before,” noted presenter Elmar Jaeckel, MD, Hannover Medical School, Hannover, Germany, in a poster presented here on November 5.
In this study, patients were allowed the choice of 2 currently approved and available protease inhibitors, utilising dual therapy with pegylated interferon alfa-2a and ribavirin or triple therapy with the inclusion of telaprevir. The choice of therapy, drug dose, and duration of therapy were at the discretion of the physician.
Dr. Jaeckel and colleagues examined 5,716 patients treated in private practice by German gastroenterologists since 2011 with the dual therapy (n = 4,501) or the telaprevir-based triple therapy (n = 1,873). The results presented here are interim data from 421 patients treated with the triple-drug combination who had completed follow-up.
The 421 patients were evaluated for metabolic risk markers and their influence on early virologic response (EVR, defined as HCV-RNA <10 IU/mL at week 4 after therapy), rapid virologic response (RVR; negative HCV-RNA at week 4 after therapy), and SVR (HCV-RNA <10 IU/mL at least 12 weeks after therapy).
SVR, it was observed, was greatly influenced by the metabolic markers. Patients with pre-diabetic alterations of glucose metabolism (evident as fasting glucose levels over 100 mg/dL) displayed diminished SVR compared with those with unaltered glucose metabolism (43.9% vs 64.1%; P = .020). The same trend held for those with glycated haemoglobin (HbA1c) of 6.0% or greater (30.8%) versus those with 6.0% or less (59.7%) (P = .057).
SVR rates were decreased in those diagnosed with diabetes mellitus compared with those without diabetes (27.3% vs 55.7%; P = .009). SVR was also reduced according to triglyceride levels >150 mg/dL (37.5% vs 55.8%;P = .050), HDL levels under 40 mg/dL (23.5% vs 60.5%; P = .006), and hypertension (43.8% vs 56.8%; P = .009).
EVR was not appreciably influenced by risk markers of metabolic syndrome. RVR, however, was diminished for patients with HbA1c level ≥ 6% compared with those with a level under 6% (30.8% vs 67.3%; P = .016), diabetes mellitus (40.9% vs 66.0%; P = .018), and high-density lipoprotein levels below 40 mg/dL (35.7% vs 67.1%; P = .028).
Patients in this interim analysis were predominantly male (63.2%), with a median age of 48.7 years. Median body mass index (BMI) was 25.9, with 25.2% of patients having a BMI ≥ 28. Duration of infection was 17.2 years, with a viral load exceeding 400,000 IU/mL in 73.6% of patients. Blood glucose levels exceeded 100 mg/dL in 20.7% of patients.
Metabolic syndrome has been linked with reduced efficacy of dual therapy involving pegylated interferon alfa-2a and ribavirin. No such association was reported, however, in phase 3 studies involving triple therapy with telaprevir.
The researchers expressed hope that the novelty of the findings, despite prior phase 3 studies, will help identify hard-to-treat patients who will need other, more efficacious, therapies.
Funding for this study was provided by Roche Pharma AG, Grenzach-Wyhlen, Germany.
[Presentation title: Elevated Glucose, Metabolic Syndrome and Diabetes Predict Lower Treatment Response to Triple Therapy With Telaprevir. Abstract 1948]