User login
MAUI, HAWAII – With three highly effective, guideline-recommended nucleoside/tide therapies for chronic hepatitis B virus (HBV) infection now available, the selection of the optimal antiviral agent for a given patient can seem daunting.
Norah Terrault, MD, offered guidance on this score at the Gastroenterology Updates, IBD, Liver Disease meeting.
As the current guidelines of the American Association for the Study of Liver Disease and European Association for the Study of the Liver make clear, these agents are to be used in targeting patients with active disease, defined by elevated alanine aminotransferase and HBV DNA levels and/or advanced fibrosis. These antivirals aim at long-term HBV control rather than disease cure.
Although numerous investigational drugs are in development with a focus on cure, the day of curative therapy has not yet arrived, noted Dr. Terrault, a professor of medicine and the director of the viral hepatitis center at the University of California, San Francisco.
Randomized trials presented at the 2017 annual meeting of European Association for the Study of the Liver demonstrated that the newest agent, tenofovir alafenamide (TAF), was as effective as tenofovir disoproxil fumarate (TDF) at suppressing HBV DNA through 96 weeks in both hepatitis B e-antigen (HBeAg)–negative and HBeAg-positive patients.
Moreover, TAF had a small but statistically significant advantage in terms of seroconversion rate at week 96 in the HBeAg-positive group, by a margin of 18%-12%. The alanine aminotransferase normalization rate was also significantly higher in the TAF group, by a margin of 81%-71% in HBeAg-negative patients and 75%-68% in HBeAg-positive patients.
“This [TAF] is a very good drug, a nice one to have at our disposal,” according to Dr. Terrault. “The primary reason we wanted it has to do with its safety profile.”
Its potential benefit in this regard was illustrated in a pair of multinational phase 3 clinical trials totaling nearly 1,300 patients with chronic HBV presented at the 2017 meeting of American Association for the Study of Liver Disease. After completing 96 weeks of double-blind treatment with TAF or TDF, everyone was switched to open-label TAF.
“There was a nice rebound in creatinine clearance and bone density when the switch was made from TDF to TAF,” she observed. “This is encouraging data for us, in that if you have a patient on TDF and you are concerned about renal or bone safety, you can do the switch to TAF and very quickly see some recovery in those abnormalities.”
Dr. Terrault offered the following guidance in selecting HBV therapy: For most patients with no comorbidities, monotherapy with either TAF, TDF, or entecavir is an excellent approach.
However, in a patient who has preexisting bone or renal disease – or who is at increased risk for such disease based upon age greater than 60 years, a history of fragility fractures, chronic systemic corticosteroid therapy, or renal abnormalities – entecavir or TAF is a better option than TDF.
TAF becomes the preferred choice over entecavir if the patient has previously been exposed to a nucleoside or if the patient is coinfected with HIV because the drug is approved for treatment of HIV and HBV, while entecavir is not.
Also, no dose adjustment of TAF is needed so long as the creatinine clearance is at least 15 mL/min, whereas the dose-adjustment threshold is 50 mL/min for both entecavir and TDF.
Conversely, entecavir, an older and less expensive drug than TAF, deserves priority in a patient with no prior exposure to a nucleoside, no HIV coinfection, or in an individual with a creatinine clearance below 15 mL/min after dose adjustment. TAF hasn’t been studied in patients with a creatinine clearance that low.
Also, TAF has not been studied in pregnant women or in patients with decompensated cirrhosis, the hepatologist noted.
Dr. Terrault serves as a consultant to AbbVie, Biotest, CoCrystal Pharmaceuticals, and Gilead Sciences.
MAUI, HAWAII – With three highly effective, guideline-recommended nucleoside/tide therapies for chronic hepatitis B virus (HBV) infection now available, the selection of the optimal antiviral agent for a given patient can seem daunting.
Norah Terrault, MD, offered guidance on this score at the Gastroenterology Updates, IBD, Liver Disease meeting.
As the current guidelines of the American Association for the Study of Liver Disease and European Association for the Study of the Liver make clear, these agents are to be used in targeting patients with active disease, defined by elevated alanine aminotransferase and HBV DNA levels and/or advanced fibrosis. These antivirals aim at long-term HBV control rather than disease cure.
Although numerous investigational drugs are in development with a focus on cure, the day of curative therapy has not yet arrived, noted Dr. Terrault, a professor of medicine and the director of the viral hepatitis center at the University of California, San Francisco.
Randomized trials presented at the 2017 annual meeting of European Association for the Study of the Liver demonstrated that the newest agent, tenofovir alafenamide (TAF), was as effective as tenofovir disoproxil fumarate (TDF) at suppressing HBV DNA through 96 weeks in both hepatitis B e-antigen (HBeAg)–negative and HBeAg-positive patients.
Moreover, TAF had a small but statistically significant advantage in terms of seroconversion rate at week 96 in the HBeAg-positive group, by a margin of 18%-12%. The alanine aminotransferase normalization rate was also significantly higher in the TAF group, by a margin of 81%-71% in HBeAg-negative patients and 75%-68% in HBeAg-positive patients.
“This [TAF] is a very good drug, a nice one to have at our disposal,” according to Dr. Terrault. “The primary reason we wanted it has to do with its safety profile.”
Its potential benefit in this regard was illustrated in a pair of multinational phase 3 clinical trials totaling nearly 1,300 patients with chronic HBV presented at the 2017 meeting of American Association for the Study of Liver Disease. After completing 96 weeks of double-blind treatment with TAF or TDF, everyone was switched to open-label TAF.
“There was a nice rebound in creatinine clearance and bone density when the switch was made from TDF to TAF,” she observed. “This is encouraging data for us, in that if you have a patient on TDF and you are concerned about renal or bone safety, you can do the switch to TAF and very quickly see some recovery in those abnormalities.”
Dr. Terrault offered the following guidance in selecting HBV therapy: For most patients with no comorbidities, monotherapy with either TAF, TDF, or entecavir is an excellent approach.
However, in a patient who has preexisting bone or renal disease – or who is at increased risk for such disease based upon age greater than 60 years, a history of fragility fractures, chronic systemic corticosteroid therapy, or renal abnormalities – entecavir or TAF is a better option than TDF.
TAF becomes the preferred choice over entecavir if the patient has previously been exposed to a nucleoside or if the patient is coinfected with HIV because the drug is approved for treatment of HIV and HBV, while entecavir is not.
Also, no dose adjustment of TAF is needed so long as the creatinine clearance is at least 15 mL/min, whereas the dose-adjustment threshold is 50 mL/min for both entecavir and TDF.
Conversely, entecavir, an older and less expensive drug than TAF, deserves priority in a patient with no prior exposure to a nucleoside, no HIV coinfection, or in an individual with a creatinine clearance below 15 mL/min after dose adjustment. TAF hasn’t been studied in patients with a creatinine clearance that low.
Also, TAF has not been studied in pregnant women or in patients with decompensated cirrhosis, the hepatologist noted.
Dr. Terrault serves as a consultant to AbbVie, Biotest, CoCrystal Pharmaceuticals, and Gilead Sciences.
MAUI, HAWAII – With three highly effective, guideline-recommended nucleoside/tide therapies for chronic hepatitis B virus (HBV) infection now available, the selection of the optimal antiviral agent for a given patient can seem daunting.
Norah Terrault, MD, offered guidance on this score at the Gastroenterology Updates, IBD, Liver Disease meeting.
As the current guidelines of the American Association for the Study of Liver Disease and European Association for the Study of the Liver make clear, these agents are to be used in targeting patients with active disease, defined by elevated alanine aminotransferase and HBV DNA levels and/or advanced fibrosis. These antivirals aim at long-term HBV control rather than disease cure.
Although numerous investigational drugs are in development with a focus on cure, the day of curative therapy has not yet arrived, noted Dr. Terrault, a professor of medicine and the director of the viral hepatitis center at the University of California, San Francisco.
Randomized trials presented at the 2017 annual meeting of European Association for the Study of the Liver demonstrated that the newest agent, tenofovir alafenamide (TAF), was as effective as tenofovir disoproxil fumarate (TDF) at suppressing HBV DNA through 96 weeks in both hepatitis B e-antigen (HBeAg)–negative and HBeAg-positive patients.
Moreover, TAF had a small but statistically significant advantage in terms of seroconversion rate at week 96 in the HBeAg-positive group, by a margin of 18%-12%. The alanine aminotransferase normalization rate was also significantly higher in the TAF group, by a margin of 81%-71% in HBeAg-negative patients and 75%-68% in HBeAg-positive patients.
“This [TAF] is a very good drug, a nice one to have at our disposal,” according to Dr. Terrault. “The primary reason we wanted it has to do with its safety profile.”
Its potential benefit in this regard was illustrated in a pair of multinational phase 3 clinical trials totaling nearly 1,300 patients with chronic HBV presented at the 2017 meeting of American Association for the Study of Liver Disease. After completing 96 weeks of double-blind treatment with TAF or TDF, everyone was switched to open-label TAF.
“There was a nice rebound in creatinine clearance and bone density when the switch was made from TDF to TAF,” she observed. “This is encouraging data for us, in that if you have a patient on TDF and you are concerned about renal or bone safety, you can do the switch to TAF and very quickly see some recovery in those abnormalities.”
Dr. Terrault offered the following guidance in selecting HBV therapy: For most patients with no comorbidities, monotherapy with either TAF, TDF, or entecavir is an excellent approach.
However, in a patient who has preexisting bone or renal disease – or who is at increased risk for such disease based upon age greater than 60 years, a history of fragility fractures, chronic systemic corticosteroid therapy, or renal abnormalities – entecavir or TAF is a better option than TDF.
TAF becomes the preferred choice over entecavir if the patient has previously been exposed to a nucleoside or if the patient is coinfected with HIV because the drug is approved for treatment of HIV and HBV, while entecavir is not.
Also, no dose adjustment of TAF is needed so long as the creatinine clearance is at least 15 mL/min, whereas the dose-adjustment threshold is 50 mL/min for both entecavir and TDF.
Conversely, entecavir, an older and less expensive drug than TAF, deserves priority in a patient with no prior exposure to a nucleoside, no HIV coinfection, or in an individual with a creatinine clearance below 15 mL/min after dose adjustment. TAF hasn’t been studied in patients with a creatinine clearance that low.
Also, TAF has not been studied in pregnant women or in patients with decompensated cirrhosis, the hepatologist noted.
Dr. Terrault serves as a consultant to AbbVie, Biotest, CoCrystal Pharmaceuticals, and Gilead Sciences.
EXPERT ANALYSIS FROM GUILD 2018