ACG Annual Meeting

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – A regimen containing the oral investigational protease inhibitor faldaprevir is efficacious and safe as initial treatment for chronic hepatitis C virus genotype 1, a randomized phase III trial showed.

A team led by Dr. Christophe Moreno, a gastroenterologist at the Erasme Hospital, Université Libre de Bruxelles, Brussels, conducted the trial, known as STARTverso 1, among 652 patients in Europe and Japan.

More than three-fourths of patients given a faldaprevir-containing interferon-based regimen had achieved a sustained virologic response at 12 weeks after the end of treatment (SVR12). This compared with only about half of patients given a placebo-containing regimen, Dr. Moreno reported at the annual meeting of the American College of Gastroenterology.

A low dose of faldaprevir worked just as well as a high one. In addition, most faldaprevir-treated patients met criteria for early treatment success and were therefore able to stop treatment after half the full duration.

The rate of serious adverse events was similarly low across treatment groups, and rates of most laboratory abnormalities were comparable.

"Faldaprevir is highly efficacious in European and Japanese patients infected with HCV [hepatitis C virus] genotype 1. Almost 90% of patients treated with faldaprevir were eligible for a shortened treatment duration of 24 weeks," Dr. Moreno commented. "Faldaprevir was well tolerated with few discontinuations due to adverse events at both dosages."

"Since this was primarily a European and Japanese study, there were no patients from this country [the United States], with African American ethnicity, which is one of the negative predictors of response," noted session comoderator Dr. Zobair N. Younossi, executive director of the center for liver diseases at Inova Fairfax Hospital, Falls Church, Va.

"Do you think that that would change [the results], if you ran the trial in this country and had 20%-30% of patients with African American ethnicity?" he asked.

Two-thirds of the patients in the trial had HCV genotype 1b, Dr. Moreno replied. "As genotype 1a is more frequent in the U.S. and African Americans, we can suppose that maybe the results would be quite different.

"There is another trial, STARTverso 2, which is evaluating the efficacy of faldaprevir in patients from the U.S., Canada, and also other countries," he added.

The investigators enrolled in STARTverso 1 patients with treatment-naive HCV genotype 1and randomized them in 1:2:2 ratio to 24 weeks of pegylated interferon alfa-2a and ribavirin plus placebo for 24 weeks (arm 1), plus faldaprevir 120 mg once daily for 12 or 24 weeks depending on response (arm 2), or plus faldaprevir 240 mg once daily for 12 weeks (arm 3).

Patients meeting criteria for early treatment success (HCV RNA less than 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped treatment at week 24. Patients who did not meet these criteria and all patients in arm 1 received interferon and ribavirin out to 48 weeks.

The main trial results showed that the rate of SVR12 was higher in both the high-dose faldaprevir group (80%) and the low-dose faldaprevir group (79%) than in the placebo group (52%, P less than .0001 for both comparisons).

Fully 87% of patients treated with low-dose faldaprevir and 89% treated with high-dose faldaprevir achieved early treatment success and therefore qualified for the shortened treatment duration of 24 weeks. Among these patients, 86% and 89%, respectively, achieved SVR12.

Just 1% of all patients treated with faldaprevir had a primary nonresponse. About 4%-10% of patients had a viral breakthrough, and 6%-15% had a relapse.

"Common baseline polymorphisms were not found to affect the efficacy of faldaprevir," Dr. Moreno commented. In particular, the drug worked equally well in the 23% of patients with genotype 1a who had the Q80K polymorphism, which has been found to reduce the efficacy of other protease inhibitors.

"The high dose of faldaprevir showed no benefit over the 120-mg dose in any subgroup analyzed," he added.

The rate of serious adverse events was 7% with both doses of faldaprevir and 6% with placebo. Moderate or worse gastrointestinal adverse effects were more common with faldaprevir (7%-12%) than with placebo (3%).

Rates of grade 3 or higher laboratory abnormalities were largely the same. The faldaprevir groups had a higher rate of hyperbilirubinemia (12%-53% vs. 1%); however, "bilirubin elevations were benign and transient," Dr. Moreno noted.

Compared with placebo, faldaprevir was not associated with an increase in the incidence of anemia, one of the leading adverse effects of first-generation protease inhibitors.

Dr. Moreno disclosed that he is a board member for Janssen, Gilead, MSD, and Bristol-Myers Squibb; is a consultant for Janssen and MSD; receives grants from Janssen, MSD, Roche, and Novartis; is on the speakers’ bureau for MSD, Janssen, and BMS; and receives travel support from Janssen, Gilead, MSD, and Novartis. The trial was sponsored by Boehringer Ingelheim Pharmaceuticals. Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.

*This article was updated October 30, 2013.

SAN DIEGO – Commonly used pain medications increase the risk of exacerbations of Crohn’s disease, judging from the findings of a prospective cohort study of nearly 800 patients with inflammatory bowel disease initially in remission.

Patients with Crohn’s disease who used nonsteroidal anti-inflammatory drugs (NSAIDs) at least five times monthly were 65% more likely to have active disease 6 months later, investigators reported at the annual meeting of the American College of Gastroenterology. Unexpectedly, any use of acetaminophen was also an independent risk factor in this group.

"A lot of our patients in remission are taking these medications. We need to ask detailed histories about this," she added. It is noteworthy that no such effect was seen in ulcerative colitis patients. "There might be a dose/response issue here. We have a lot of young women obviously with inflammatory bowel disease who take ibuprofen for menstrual cramping." When taken fewer than five times monthly, these drugs do not seem to have an effect, she noted.

"Implications may be that the requirement for any pain medication while in remission may actually be a marker of occult ongoing disease. Occult disease itself may be the risk factor for disease activity," commented lead investigator Dr. Millie Long, an assistant professor at the University of North Carolina, Chapel Hill.

"It’s also theoretically possible that a mechanism common to both drugs may be associated with increased disease activity," she added. For example, both NSAIDs and acetaminophen inhibit cyclooxygenase-3.

"Further prospective studies are needed with objective inflammatory outcomes to better assess the risks of these pain medications and better counsel patients," Dr. Long maintained.

One audience member noted that the study could not tease apart whether analgesic use was the cause or the result of an exacerbation.

"I would argue that we specifically limited this to a population of patients in remission by validated disease activity indices at baseline. ... We also had data on the quality of life of these individuals, the Shortened Inflammatory Bowel Disease questionnaire. These were individuals who felt well," Dr. Long replied. "That said, they could have been taking their pain medication for gut pain, I agree. They could have been taking it for arthritis, they could have been taking it for a headache."

Session comoderator Dr. Miguel D. Regueiro, a gastroenterologist at the University of Pittsburgh, asked, "In your practice, will you allow Crohn’s patients to take an NSAID three or four times a month?"

"I do, particularly for my young women who really need it for menstrual cramping. I don’t think that one time a week – and obviously these data support that – is going to cause a problem," Dr. Long replied. "I do feel these data as well as the Bonner prospective cohort data [Inflamm. Bowel Dis. 2004;10:751-57] show that high-dose NSAIDs may be bad news in patients with Crohn’s disease."

The investigators conducted the study among Crohn’s and Colitis Foundation of America (CCFA) Partners, an Internet-based cohort of patients with inflammatory bowel disease. The patients completed online surveys at baseline and 6 months, answering questions about disease activity and average number of times per month they used various pain medications.

Analyses were based on 791 patients who were in remission at baseline. About 75% had Crohn’s disease, reported Dr. Long. The mean duration of inflammatory bowel disease was approximately 14 years.

Overall, 43% of patients reported using any NSAIDs, and 19% reported using them at least five times monthly. Additionally, 65% reported any use of acetaminophen.

At follow-up, about a fifth of patients overall had experienced an exacerbation and now had active disease, defined as a simplified Crohn’s Disease Activity Index (sCDAI) score of at least 150 or a Simple Clinical Colitis Activity Index (SCCAI) score of greater than 2.

In the cohort as a whole, the proportion of patients with an exacerbation did not vary significantly according NSAID use, but it was higher among acetaminophen users versus nonusers (20% vs. 14%; P = .03).

Analyses stratified by type of disease showed that patients with Crohn’s disease were more likely to have an exacerbation if they used NSAIDs at least five times monthly versus less often, and if they used acetaminophen at all. In contrast, patients with ulcerative colitis were not affected.

In multivariate analyses that controlled for potential confounders, including use of other medications, NSAID use five or more times monthly was an independent risk factor for exacerbation in the entire cohort (relative risk, 1.46) and in the subset with Crohn’s disease (RR, 1.65).

Any use of acetaminophen was also an independent risk factor, both in the entire cohort (RR, 1.41) and in the subset with Crohn’s disease (RR, 1.72).

Dr. Long disclosed no relevant conflicts of interest.

SAN DIEGO – Commonly used pain medications increase the risk of exacerbations of Crohn’s disease, judging from the findings of a prospective cohort study of nearly 800 patients with inflammatory bowel disease initially in remission.

Patients with Crohn’s disease who used nonsteroidal anti-inflammatory drugs (NSAIDs) at least five times monthly were 65% more likely to have active disease 6 months later, investigators reported at the annual meeting of the American College of Gastroenterology. Unexpectedly, any use of acetaminophen was also an independent risk factor in this group.

"A lot of our patients in remission are taking these medications. We need to ask detailed histories about this," she added. It is noteworthy that no such effect was seen in ulcerative colitis patients. "There might be a dose/response issue here. We have a lot of young women obviously with inflammatory bowel disease who take ibuprofen for menstrual cramping." When taken fewer than five times monthly, these drugs do not seem to have an effect, she noted.

"Implications may be that the requirement for any pain medication while in remission may actually be a marker of occult ongoing disease. Occult disease itself may be the risk factor for disease activity," commented lead investigator Dr. Millie Long, an assistant professor at the University of North Carolina, Chapel Hill.

"It’s also theoretically possible that a mechanism common to both drugs may be associated with increased disease activity," she added. For example, both NSAIDs and acetaminophen inhibit cyclooxygenase-3.

"Further prospective studies are needed with objective inflammatory outcomes to better assess the risks of these pain medications and better counsel patients," Dr. Long maintained.

One audience member noted that the study could not tease apart whether analgesic use was the cause or the result of an exacerbation.

"I would argue that we specifically limited this to a population of patients in remission by validated disease activity indices at baseline. ... We also had data on the quality of life of these individuals, the Shortened Inflammatory Bowel Disease questionnaire. These were individuals who felt well," Dr. Long replied. "That said, they could have been taking their pain medication for gut pain, I agree. They could have been taking it for arthritis, they could have been taking it for a headache."

Session comoderator Dr. Miguel D. Regueiro, a gastroenterologist at the University of Pittsburgh, asked, "In your practice, will you allow Crohn’s patients to take an NSAID three or four times a month?"

"I do, particularly for my young women who really need it for menstrual cramping. I don’t think that one time a week – and obviously these data support that – is going to cause a problem," Dr. Long replied. "I do feel these data as well as the Bonner prospective cohort data [Inflamm. Bowel Dis. 2004;10:751-57] show that high-dose NSAIDs may be bad news in patients with Crohn’s disease."

The investigators conducted the study among Crohn’s and Colitis Foundation of America (CCFA) Partners, an Internet-based cohort of patients with inflammatory bowel disease. The patients completed online surveys at baseline and 6 months, answering questions about disease activity and average number of times per month they used various pain medications.

Analyses were based on 791 patients who were in remission at baseline. About 75% had Crohn’s disease, reported Dr. Long. The mean duration of inflammatory bowel disease was approximately 14 years.

Overall, 43% of patients reported using any NSAIDs, and 19% reported using them at least five times monthly. Additionally, 65% reported any use of acetaminophen.

At follow-up, about a fifth of patients overall had experienced an exacerbation and now had active disease, defined as a simplified Crohn’s Disease Activity Index (sCDAI) score of at least 150 or a Simple Clinical Colitis Activity Index (SCCAI) score of greater than 2.

In the cohort as a whole, the proportion of patients with an exacerbation did not vary significantly according NSAID use, but it was higher among acetaminophen users versus nonusers (20% vs. 14%; P = .03).

Analyses stratified by type of disease showed that patients with Crohn’s disease were more likely to have an exacerbation if they used NSAIDs at least five times monthly versus less often, and if they used acetaminophen at all. In contrast, patients with ulcerative colitis were not affected.

In multivariate analyses that controlled for potential confounders, including use of other medications, NSAID use five or more times monthly was an independent risk factor for exacerbation in the entire cohort (relative risk, 1.46) and in the subset with Crohn’s disease (RR, 1.65).

Any use of acetaminophen was also an independent risk factor, both in the entire cohort (RR, 1.41) and in the subset with Crohn’s disease (RR, 1.72).

Dr. Long disclosed no relevant conflicts of interest.

SAN DIEGO – Commonly used pain medications increase the risk of exacerbations of Crohn’s disease, judging from the findings of a prospective cohort study of nearly 800 patients with inflammatory bowel disease initially in remission.

Patients with Crohn’s disease who used nonsteroidal anti-inflammatory drugs (NSAIDs) at least five times monthly were 65% more likely to have active disease 6 months later, investigators reported at the annual meeting of the American College of Gastroenterology. Unexpectedly, any use of acetaminophen was also an independent risk factor in this group.

"A lot of our patients in remission are taking these medications. We need to ask detailed histories about this," she added. It is noteworthy that no such effect was seen in ulcerative colitis patients. "There might be a dose/response issue here. We have a lot of young women obviously with inflammatory bowel disease who take ibuprofen for menstrual cramping." When taken fewer than five times monthly, these drugs do not seem to have an effect, she noted.

"Implications may be that the requirement for any pain medication while in remission may actually be a marker of occult ongoing disease. Occult disease itself may be the risk factor for disease activity," commented lead investigator Dr. Millie Long, an assistant professor at the University of North Carolina, Chapel Hill.

"It’s also theoretically possible that a mechanism common to both drugs may be associated with increased disease activity," she added. For example, both NSAIDs and acetaminophen inhibit cyclooxygenase-3.

"Further prospective studies are needed with objective inflammatory outcomes to better assess the risks of these pain medications and better counsel patients," Dr. Long maintained.

One audience member noted that the study could not tease apart whether analgesic use was the cause or the result of an exacerbation.

"I would argue that we specifically limited this to a population of patients in remission by validated disease activity indices at baseline. ... We also had data on the quality of life of these individuals, the Shortened Inflammatory Bowel Disease questionnaire. These were individuals who felt well," Dr. Long replied. "That said, they could have been taking their pain medication for gut pain, I agree. They could have been taking it for arthritis, they could have been taking it for a headache."

Session comoderator Dr. Miguel D. Regueiro, a gastroenterologist at the University of Pittsburgh, asked, "In your practice, will you allow Crohn’s patients to take an NSAID three or four times a month?"

"I do, particularly for my young women who really need it for menstrual cramping. I don’t think that one time a week – and obviously these data support that – is going to cause a problem," Dr. Long replied. "I do feel these data as well as the Bonner prospective cohort data [Inflamm. Bowel Dis. 2004;10:751-57] show that high-dose NSAIDs may be bad news in patients with Crohn’s disease."

The investigators conducted the study among Crohn’s and Colitis Foundation of America (CCFA) Partners, an Internet-based cohort of patients with inflammatory bowel disease. The patients completed online surveys at baseline and 6 months, answering questions about disease activity and average number of times per month they used various pain medications.

Analyses were based on 791 patients who were in remission at baseline. About 75% had Crohn’s disease, reported Dr. Long. The mean duration of inflammatory bowel disease was approximately 14 years.

Overall, 43% of patients reported using any NSAIDs, and 19% reported using them at least five times monthly. Additionally, 65% reported any use of acetaminophen.

At follow-up, about a fifth of patients overall had experienced an exacerbation and now had active disease, defined as a simplified Crohn’s Disease Activity Index (sCDAI) score of at least 150 or a Simple Clinical Colitis Activity Index (SCCAI) score of greater than 2.

In the cohort as a whole, the proportion of patients with an exacerbation did not vary significantly according NSAID use, but it was higher among acetaminophen users versus nonusers (20% vs. 14%; P = .03).

Analyses stratified by type of disease showed that patients with Crohn’s disease were more likely to have an exacerbation if they used NSAIDs at least five times monthly versus less often, and if they used acetaminophen at all. In contrast, patients with ulcerative colitis were not affected.

In multivariate analyses that controlled for potential confounders, including use of other medications, NSAID use five or more times monthly was an independent risk factor for exacerbation in the entire cohort (relative risk, 1.46) and in the subset with Crohn’s disease (RR, 1.65).

Any use of acetaminophen was also an independent risk factor, both in the entire cohort (RR, 1.41) and in the subset with Crohn’s disease (RR, 1.72).

Dr. Long disclosed no relevant conflicts of interest.