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Prioritization for interferon-free regimens and potential drug interactions of current direct-acting anti-hepatitis C agents in routine clinical practice.
BACKGROUND: We determined the proportions of patients with chronic hepatitis C (CHC) in association with possible prioritized indications for interferon-free regimens and the use of co-medications with potential drug-drug interactions (DDIs).
METHODS: Five hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure. All co-medications were classified into those with no DDIs/no clear data for DDIs, potential DDIs, and contraindication due to DDI for each agent, according to the HEP Drug Interaction Checker.
RESULTS: Of the 500 patients, 1% had undergone liver transplantation, whereas 6.6% had decompensated cirrhosis, 21.8% F4, 17.1% F3, 10.4% F2, and 34.8% F0-1 fibrosis. Contraindications for interferon were present in 38.5% of non-transplant patients with compensated liver disease. The probability of contraindications/potential DDIs was greater for boceprevir/telaprevir and ombitasvir/paritaprevir/ritonavir±dasabuvir, compared to all other agents (P<0.001), and least for sofosbuvir (P<0.05). Contraindications/potential DDIs were more frequently present in patients ≥50 than <50 years old (P≤0.034), and more common in F3-4 than F0-2, and F4 than F0-3 fibrosis (P≤0.019) for all direct-acting antivirals (DAAs).
CONCLUSIONS: The expansion of the criteria for prioritization of interferon-free regimens from cirrhosis to F3 and perhaps F2 fibrosis will increase the proportion of patients with DAA access by only 10-15% and 10%, respectively. A potential for DDIs is frequently present with protease inhibitors, but also exists with other DAAs. The probability of DDIs is higher in patients with priority for DAAs, including those who have advanced liver disease and are usually of older age.
METHODS: Five hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure. All co-medications were classified into those with no DDIs/no clear data for DDIs, potential DDIs, and contraindication due to DDI for each agent, according to the HEP Drug Interaction Checker.
RESULTS: Of the 500 patients, 1% had undergone liver transplantation, whereas 6.6% had decompensated cirrhosis, 21.8% F4, 17.1% F3, 10.4% F2, and 34.8% F0-1 fibrosis. Contraindications for interferon were present in 38.5% of non-transplant patients with compensated liver disease. The probability of contraindications/potential DDIs was greater for boceprevir/telaprevir and ombitasvir/paritaprevir/ritonavir±dasabuvir, compared to all other agents (P<0.001), and least for sofosbuvir (P<0.05). Contraindications/potential DDIs were more frequently present in patients ≥50 than <50 years old (P≤0.034), and more common in F3-4 than F0-2, and F4 than F0-3 fibrosis (P≤0.019) for all direct-acting antivirals (DAAs).
CONCLUSIONS: The expansion of the criteria for prioritization of interferon-free regimens from cirrhosis to F3 and perhaps F2 fibrosis will increase the proportion of patients with DAA access by only 10-15% and 10%, respectively. A potential for DDIs is frequently present with protease inhibitors, but also exists with other DAAs. The probability of DDIs is higher in patients with priority for DAAs, including those who have advanced liver disease and are usually of older age.
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