Viekira Pak safe for patients with HCV, Child-Pugh A cirrhosis

Patients with hepatitis C and Child-Pugh A cirrhosis had similar rates of treatment-related adverse events and lower rates of hepatic decompensation after treatment with Viekira Pak compared with untreated patients, according to recently published data. However, those with a history of advanced cirrhosis were more likely to experience treatment-related adverse events.

“Importantly, many of the events consistent with hepatic decompensation were self-limiting and improved without treatment interruption, or occurred at time points not typically associated with drug toxicity,” Fred Poordad, MD, from the Texas Liver Institute and University of Texas Health Science Center, San Antonio, and colleagues wrote.

The researchers pooled safety data from 12 phase 2 and phase 3 studies that included patients with HCV and compensated cirrhosis who received Viekira Pak (ombitasvir/paritaprevir/ritonavir, AbbVie) or ombitasvir/paritaprevir/ritonavir with dasabuvir, with or without ribavirin in either case.

Of the 1,066 patients included in the pooled safety assessment, 846 received ribavirin and 480 were HCV treatment-naive. Patients had a baseline Child-Pugh score of five (n = 891), six (n = 130) or seven (n = 19).

Overall, the rate of serious treatment-related adverse events was 5.3% (95% CI, 4.1-6.8) and the rate of serious treatment-related events that led to treatment discontinuation was 2.2% (95% CI, 1.4-3.2). Serious treatment-related adverse events, including those that led to treatment discontinuation, were less frequent among the 62 patients who received ombitasvir/paritaprevir/ritonavir with dasabuvir and without ribavirin.

Thirteen patients experienced a treatment-related adverse event that the researchers considered consistent with hepatic decompensation. Eleven of those 13 received ribavirin with treatment.

The 13 hepatic decompensation events resolved in nine patients — including six who continued treatment — were ongoing in two patients after follow-up, and led to death in one patient. One patient’s outcome was unknown.

Compared with those who experienced a treatment-related adverse event consistent with hepatic decompensation, those who did not had a higher frequency Child-Pugh score of six or higher at baseline, platelet count of less than 90 x 109 cells/L, and serum albumin levels less than 3.5 g/dL.

“Given that hepatic decompensation events have been reported in association with multiple classes of [direct-acting antivirals], it is unclear whether direct toxicity of DAAs, including protease inhibitors, is responsible for these events. Another possibility is that hepatic decompensation events reported with DAAs are unrelated to therapy and are instead simply part of the natural history of advanced liver disease caused by HCV infection,” the researchers wrote. “More data are needed to establish whether there is a causal relationship between this and other classes of DAA and events of hepatic decompensation.” – by Talitha Bennett

Disclosure: Poordad reports he received grants or research support from AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, BMS, Genentech, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Medarex, Medtronic, Merck, Novartis, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Vertex Pharmaceuticals and ZymoGenetics; is a speaker for Gilead, Kadmon, Merck, Onyx/Bayer, Genentech, GlaxoSmithKline, Salix, and Vertex; and is a consultant or advisor for AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, BMS, Gilead, GlaxoSmithKline, GlobeImmune, Idenix, Merck, Novartis, Tibotec/Janssen, Theravance and Vertex. Please see the full study for the other authors’ relevant financial disclosures.

Patients with hepatitis C and Child-Pugh A cirrhosis had similar rates of treatment-related adverse events and lower rates of hepatic decompensation after treatment with Viekira Pak compared with untreated patients, according to recently published data. However, those with a history of advanced cirrhosis were more likely to experience treatment-related adverse events.

“Importantly, many of the events consistent with hepatic decompensation were self-limiting and improved without treatment interruption, or occurred at time points not typically associated with drug toxicity,” Fred Poordad, MD, from the Texas Liver Institute and University of Texas Health Science Center, San Antonio, and colleagues wrote.

The researchers pooled safety data from 12 phase 2 and phase 3 studies that included patients with HCV and compensated cirrhosis who received Viekira Pak (ombitasvir/paritaprevir/ritonavir, AbbVie) or ombitasvir/paritaprevir/ritonavir with dasabuvir, with or without ribavirin in either case.

Of the 1,066 patients included in the pooled safety assessment, 846 received ribavirin and 480 were HCV treatment-naive. Patients had a baseline Child-Pugh score of five (n = 891), six (n = 130) or seven (n = 19).

Overall, the rate of serious treatment-related adverse events was 5.3% (95% CI, 4.1-6.8) and the rate of serious treatment-related events that led to treatment discontinuation was 2.2% (95% CI, 1.4-3.2). Serious treatment-related adverse events, including those that led to treatment discontinuation, were less frequent among the 62 patients who received ombitasvir/paritaprevir/ritonavir with dasabuvir and without ribavirin.

Thirteen patients experienced a treatment-related adverse event that the researchers considered consistent with hepatic decompensation. Eleven of those 13 received ribavirin with treatment.

The 13 hepatic decompensation events resolved in nine patients — including six who continued treatment — were ongoing in two patients after follow-up, and led to death in one patient. One patient’s outcome was unknown.

Compared with those who experienced a treatment-related adverse event consistent with hepatic decompensation, those who did not had a higher frequency Child-Pugh score of six or higher at baseline, platelet count of less than 90 x 109 cells/L, and serum albumin levels less than 3.5 g/dL.

“Given that hepatic decompensation events have been reported in association with multiple classes of [direct-acting antivirals], it is unclear whether direct toxicity of DAAs, including protease inhibitors, is responsible for these events. Another possibility is that hepatic decompensation events reported with DAAs are unrelated to therapy and are instead simply part of the natural history of advanced liver disease caused by HCV infection,” the researchers wrote. “More data are needed to establish whether there is a causal relationship between this and other classes of DAA and events of hepatic decompensation.” – by Talitha Bennett

Disclosure: Poordad reports he received grants or research support from AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, BMS, Genentech, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Medarex, Medtronic, Merck, Novartis, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Vertex Pharmaceuticals and ZymoGenetics; is a speaker for Gilead, Kadmon, Merck, Onyx/Bayer, Genentech, GlaxoSmithKline, Salix, and Vertex; and is a consultant or advisor for AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, BMS, Gilead, GlaxoSmithKline, GlobeImmune, Idenix, Merck, Novartis, Tibotec/Janssen, Theravance and Vertex. Please see the full study for the other authors’ relevant financial disclosures.