Hepatic failure flagged as unexpected boceprevir safety signal in adverse event review

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

[email protected]

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

[email protected]

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

[email protected]