DDW 2015

WASHINGTON – Performed when recommended, cholecystecomy significantly decreases the risk of near-term rehospitalization for acute biliary pancreatitis, results of a retrospective study indicate.

Among more than 23,000 patients with mild to moderate acute biliary pancreatitis, less than 2% of those who underwent cholecystectomy within 30 days, as recommended under American Gastroenterological Association guidelines, were rehospitalized for pancreatitis within 6 months. In contrast, nearly 17% of patients who had cholecystectomy after 1 month or never had it were back in the hospital within half a year, said Dr. Ayesha Kamal, a postdoctoral research fellow at the Johns Hopkins Hospital in Baltimore.

“Cholecystectomy prevents future hospitalization for biliary pancreatitis,” she said at the annual Digestive Disease Week.

The study, based on claims data, also showed that adherence to AGA guidelines is fairly high, on the order of 75%, she said.

Acute pancreatitis is one of the most common gastrointestinal diseases in the United States, accounting for about 300,000 hospitalizations in 2009, at a total cost of about $2.6 billion. Gallstone disease is the most common cause of acute pancreatitis, responsible for an estimated 40% of all cases, she said.

Guidelines from the AGA and other organizations recommend cholecystectomy either during the same hospitalization for acute biliary pancreatitis, or within 4 weeks. To see whether clinicians were adhering to the AGA guidelines and whether the guideline-recommended timing of cholecystectomy made a difference, Dr. Kamal and colleagues analyzed data from the MarketScan Commercial Claims & Encounters database, which includes individual-level clinical utilization data for both inpatient and outpatient visits paid for by employer-sponsored health plans.

They looked at data both on patients who were treated in accordance with guidelines (first hospitalization for mild to moderate acute biliary pancreatitis, with cholecystectomy performed either on the day of hospitalization or within 30 days), and outside of the guidelines (no cholecystectomy, or cholecystectomy performed later than 30 days after the index hospitalization).

They assessed recurrences within 30 days of follow-up by International Classification of Diseases, 9th Revision (ICD-9) codes for acute pancreatitis and gallstone disease.

Combing through 8.8 million adult inpatient encounters for acute biliary pancreatitis, they excluded those patients with a diagnosis of severe or chronic pancreatitis, alcohol abuse, less than 30 days of follow-up, deaths during hospitalization, discharge to hospice, and those with a length of stay longer than 30 days.

This left them with a final cohort of 23,515 patients with mild to moderate acute biliary pancreatitis.

They found that 61% of patients had cholecystectomy during their initial hospitalizations, and an additional 14% had the surgery during a subsequent hospitalization within 30 days. Of the remaining patients, 7% had cholecystectomies after 30 days, and 18% never had one.

Among patients treated under the guidelines, 1.3% who had their gallbladders removed during the initial hospitalization had a pancreatitis recurrence within 6 months, and 0.2% had a recurrence more than 6 months later.

In contrast, 36.7% of patients who had a cholecystectomy more than a month after their first hospitalization for pancreatitis had a recurrence within 6 months, and 4.5% had a recurrence after 6 months.

Among patients who never underwent cholecystectomy, the respective recurrence rates were 5.4% and 1.1%.

“One in six patients who did not receive a cholecystectomy within 30 days will be hospitalized again within 6 months,” Dr. Kamal said.

She acknowledged that the study was limited by the authors’ inability to confirm acute biliary pancreatitis with chart review, and by the limitations of the database, which is confined to adults younger than 65 with employer-sponsored medical plans.

In the question and answer portion of the presentation, Dr. Nirav Thosani, a gastroenterologist at Memorial Hermann Hospital in Houston, noted that ICD-9 codes do not distinguish between different types of pancreatitis.

“It might be possible that those patients who never had cholecystectomy never had acute biliary pancreatitis, or some other reason for acute pancreatitis, and that’s the reason for the rehospitalization,” he said.

Dr. Kamal replied that they tried to control for other causes of pancreatitis by including ICD-9 codes for gallstone disease and by excluding patients with diagnoses of alcohol abuse.

The study funding source was not disclosed. Dr. Kamal and Dr. Thosani reported having no relevant disclosures.

WASHINGTON – Performed when recommended, cholecystecomy significantly decreases the risk of near-term rehospitalization for acute biliary pancreatitis, results of a retrospective study indicate.

Among more than 23,000 patients with mild to moderate acute biliary pancreatitis, less than 2% of those who underwent cholecystectomy within 30 days, as recommended under American Gastroenterological Association guidelines, were rehospitalized for pancreatitis within 6 months. In contrast, nearly 17% of patients who had cholecystectomy after 1 month or never had it were back in the hospital within half a year, said Dr. Ayesha Kamal, a postdoctoral research fellow at the Johns Hopkins Hospital in Baltimore.

“Cholecystectomy prevents future hospitalization for biliary pancreatitis,” she said at the annual Digestive Disease Week.

The study, based on claims data, also showed that adherence to AGA guidelines is fairly high, on the order of 75%, she said.

Acute pancreatitis is one of the most common gastrointestinal diseases in the United States, accounting for about 300,000 hospitalizations in 2009, at a total cost of about $2.6 billion. Gallstone disease is the most common cause of acute pancreatitis, responsible for an estimated 40% of all cases, she said.

Guidelines from the AGA and other organizations recommend cholecystectomy either during the same hospitalization for acute biliary pancreatitis, or within 4 weeks. To see whether clinicians were adhering to the AGA guidelines and whether the guideline-recommended timing of cholecystectomy made a difference, Dr. Kamal and colleagues analyzed data from the MarketScan Commercial Claims & Encounters database, which includes individual-level clinical utilization data for both inpatient and outpatient visits paid for by employer-sponsored health plans.

They looked at data both on patients who were treated in accordance with guidelines (first hospitalization for mild to moderate acute biliary pancreatitis, with cholecystectomy performed either on the day of hospitalization or within 30 days), and outside of the guidelines (no cholecystectomy, or cholecystectomy performed later than 30 days after the index hospitalization).

They assessed recurrences within 30 days of follow-up by International Classification of Diseases, 9th Revision (ICD-9) codes for acute pancreatitis and gallstone disease.

Combing through 8.8 million adult inpatient encounters for acute biliary pancreatitis, they excluded those patients with a diagnosis of severe or chronic pancreatitis, alcohol abuse, less than 30 days of follow-up, deaths during hospitalization, discharge to hospice, and those with a length of stay longer than 30 days.

This left them with a final cohort of 23,515 patients with mild to moderate acute biliary pancreatitis.

They found that 61% of patients had cholecystectomy during their initial hospitalizations, and an additional 14% had the surgery during a subsequent hospitalization within 30 days. Of the remaining patients, 7% had cholecystectomies after 30 days, and 18% never had one.

Among patients treated under the guidelines, 1.3% who had their gallbladders removed during the initial hospitalization had a pancreatitis recurrence within 6 months, and 0.2% had a recurrence more than 6 months later.

In contrast, 36.7% of patients who had a cholecystectomy more than a month after their first hospitalization for pancreatitis had a recurrence within 6 months, and 4.5% had a recurrence after 6 months.

Among patients who never underwent cholecystectomy, the respective recurrence rates were 5.4% and 1.1%.

“One in six patients who did not receive a cholecystectomy within 30 days will be hospitalized again within 6 months,” Dr. Kamal said.

She acknowledged that the study was limited by the authors’ inability to confirm acute biliary pancreatitis with chart review, and by the limitations of the database, which is confined to adults younger than 65 with employer-sponsored medical plans.

In the question and answer portion of the presentation, Dr. Nirav Thosani, a gastroenterologist at Memorial Hermann Hospital in Houston, noted that ICD-9 codes do not distinguish between different types of pancreatitis.

“It might be possible that those patients who never had cholecystectomy never had acute biliary pancreatitis, or some other reason for acute pancreatitis, and that’s the reason for the rehospitalization,” he said.

Dr. Kamal replied that they tried to control for other causes of pancreatitis by including ICD-9 codes for gallstone disease and by excluding patients with diagnoses of alcohol abuse.

The study funding source was not disclosed. Dr. Kamal and Dr. Thosani reported having no relevant disclosures.

WASHINGTON – Performed when recommended, cholecystecomy significantly decreases the risk of near-term rehospitalization for acute biliary pancreatitis, results of a retrospective study indicate.

Among more than 23,000 patients with mild to moderate acute biliary pancreatitis, less than 2% of those who underwent cholecystectomy within 30 days, as recommended under American Gastroenterological Association guidelines, were rehospitalized for pancreatitis within 6 months. In contrast, nearly 17% of patients who had cholecystectomy after 1 month or never had it were back in the hospital within half a year, said Dr. Ayesha Kamal, a postdoctoral research fellow at the Johns Hopkins Hospital in Baltimore.

“Cholecystectomy prevents future hospitalization for biliary pancreatitis,” she said at the annual Digestive Disease Week.

The study, based on claims data, also showed that adherence to AGA guidelines is fairly high, on the order of 75%, she said.

Acute pancreatitis is one of the most common gastrointestinal diseases in the United States, accounting for about 300,000 hospitalizations in 2009, at a total cost of about $2.6 billion. Gallstone disease is the most common cause of acute pancreatitis, responsible for an estimated 40% of all cases, she said.

Guidelines from the AGA and other organizations recommend cholecystectomy either during the same hospitalization for acute biliary pancreatitis, or within 4 weeks. To see whether clinicians were adhering to the AGA guidelines and whether the guideline-recommended timing of cholecystectomy made a difference, Dr. Kamal and colleagues analyzed data from the MarketScan Commercial Claims & Encounters database, which includes individual-level clinical utilization data for both inpatient and outpatient visits paid for by employer-sponsored health plans.

They looked at data both on patients who were treated in accordance with guidelines (first hospitalization for mild to moderate acute biliary pancreatitis, with cholecystectomy performed either on the day of hospitalization or within 30 days), and outside of the guidelines (no cholecystectomy, or cholecystectomy performed later than 30 days after the index hospitalization).

They assessed recurrences within 30 days of follow-up by International Classification of Diseases, 9th Revision (ICD-9) codes for acute pancreatitis and gallstone disease.

Combing through 8.8 million adult inpatient encounters for acute biliary pancreatitis, they excluded those patients with a diagnosis of severe or chronic pancreatitis, alcohol abuse, less than 30 days of follow-up, deaths during hospitalization, discharge to hospice, and those with a length of stay longer than 30 days.

This left them with a final cohort of 23,515 patients with mild to moderate acute biliary pancreatitis.

They found that 61% of patients had cholecystectomy during their initial hospitalizations, and an additional 14% had the surgery during a subsequent hospitalization within 30 days. Of the remaining patients, 7% had cholecystectomies after 30 days, and 18% never had one.

Among patients treated under the guidelines, 1.3% who had their gallbladders removed during the initial hospitalization had a pancreatitis recurrence within 6 months, and 0.2% had a recurrence more than 6 months later.

In contrast, 36.7% of patients who had a cholecystectomy more than a month after their first hospitalization for pancreatitis had a recurrence within 6 months, and 4.5% had a recurrence after 6 months.

Among patients who never underwent cholecystectomy, the respective recurrence rates were 5.4% and 1.1%.

“One in six patients who did not receive a cholecystectomy within 30 days will be hospitalized again within 6 months,” Dr. Kamal said.

She acknowledged that the study was limited by the authors’ inability to confirm acute biliary pancreatitis with chart review, and by the limitations of the database, which is confined to adults younger than 65 with employer-sponsored medical plans.

In the question and answer portion of the presentation, Dr. Nirav Thosani, a gastroenterologist at Memorial Hermann Hospital in Houston, noted that ICD-9 codes do not distinguish between different types of pancreatitis.

“It might be possible that those patients who never had cholecystectomy never had acute biliary pancreatitis, or some other reason for acute pancreatitis, and that’s the reason for the rehospitalization,” he said.

Dr. Kamal replied that they tried to control for other causes of pancreatitis by including ICD-9 codes for gallstone disease and by excluding patients with diagnoses of alcohol abuse.

The study funding source was not disclosed. Dr. Kamal and Dr. Thosani reported having no relevant disclosures.

WASHINGTON – More intensive treatment with early combined immunosuppression was associated with a longer time to first flare and fewer flares than conventional management during long-term follow-up of patients with Crohn’s disease.

Fewer patients treated with the “top-down” approach required anti–tumor necrosis factor (anti-TNF) agents or corticosteroids during follow-up, Dr. Daniël Hoekman reported during the annual Digestive Disease Week.

Current guidelines advocate an initial “step-up” approach for Crohn’s disease that focuses on controlling symptoms with corticosteroids followed by immunomodulators and then anti-TNF inhibitors to manage the chronic relapsing-remitting course of Crohn’s.

A new strategy has been proposed with the aim of altering the disease course and slow progression by reversing the treatment paradigm from a step-up to a top-down approach. A 2-year, randomized European trial showed that a top-down approach, combining early immunosuppression with infliximab (Remicade) and azathioprine (Imuran in Canada, Azasan in the United States) followed by azathioprine monotherapy and, if necessary, additional infliximab and corticosteroids, was more effective than step-up management for induction of remission and reduction of steroids in the short term (Lancet 2008;371:660-7).

To investigate the long-term outcome of Crohn’s disease, a retrospective chart review was performed in 119 of the 133 trial participants followed for 8 years or 16 semesters (mean 14.2 semesters) after the initial 2-year trial period. Management during the present study was left to physician discretion. At the start of the extended follow-up, most patients in both the step-up and top-down groups were on immunomodulators (66% vs. 82%) and only a small portion were using infliximab (15% vs. 20%). A total of 164 endoscopy reports were available for 59% of patients.

During follow-up, significantly more patients treated with the step-up approach than the top-down approach required anti-TNF inhibitors (73% vs. 54%; P = .04) and steroids (62% vs. 41%; P = .02), said Dr. Hoekman of the Academic Medical Center, Amsterdam.

There was no difference between the step-up and top-down groups in long-term remission rates (70% vs. 73%; P = .85).

The top-down group, however, had significantly fewer flares than the step-up group (7% vs. 19%; P = .01) and a longer time to first flare (median 9 semesters vs. 5 semesters; P = .02), he said.

There were no differences between groups in rates of hospitalization or surgery for Crohn’s disease, new fistula, or rescue treatment, defined as use of cyclosporine, experimental therapy, or surgery.

A review of the endoscopy reports suggested a trend for fewer large ulcers per patient in the top-down group than the step-up group, but this did not reach statistical significance (14% vs. 24%; P = .11), Dr. Hoekman said. The median proportion of endoscopies with remission also was similar (49% vs. 43%; P = .46).

Rates of adverse events also were similar in the top-down and step-up groups including infusion reactions (14% vs. 10%), serious infection (22% vs. 10%), malignancy (0 vs. 1 event), and dysplastic lesions (0 vs. 2 events), he said.

[email protected]

On Twitter@pwendl

WASHINGTON – More intensive treatment with early combined immunosuppression was associated with a longer time to first flare and fewer flares than conventional management during long-term follow-up of patients with Crohn’s disease.

Fewer patients treated with the “top-down” approach required anti–tumor necrosis factor (anti-TNF) agents or corticosteroids during follow-up, Dr. Daniël Hoekman reported during the annual Digestive Disease Week.

Current guidelines advocate an initial “step-up” approach for Crohn’s disease that focuses on controlling symptoms with corticosteroids followed by immunomodulators and then anti-TNF inhibitors to manage the chronic relapsing-remitting course of Crohn’s.

A new strategy has been proposed with the aim of altering the disease course and slow progression by reversing the treatment paradigm from a step-up to a top-down approach. A 2-year, randomized European trial showed that a top-down approach, combining early immunosuppression with infliximab (Remicade) and azathioprine (Imuran in Canada, Azasan in the United States) followed by azathioprine monotherapy and, if necessary, additional infliximab and corticosteroids, was more effective than step-up management for induction of remission and reduction of steroids in the short term (Lancet 2008;371:660-7).

To investigate the long-term outcome of Crohn’s disease, a retrospective chart review was performed in 119 of the 133 trial participants followed for 8 years or 16 semesters (mean 14.2 semesters) after the initial 2-year trial period. Management during the present study was left to physician discretion. At the start of the extended follow-up, most patients in both the step-up and top-down groups were on immunomodulators (66% vs. 82%) and only a small portion were using infliximab (15% vs. 20%). A total of 164 endoscopy reports were available for 59% of patients.

During follow-up, significantly more patients treated with the step-up approach than the top-down approach required anti-TNF inhibitors (73% vs. 54%; P = .04) and steroids (62% vs. 41%; P = .02), said Dr. Hoekman of the Academic Medical Center, Amsterdam.

There was no difference between the step-up and top-down groups in long-term remission rates (70% vs. 73%; P = .85).

The top-down group, however, had significantly fewer flares than the step-up group (7% vs. 19%; P = .01) and a longer time to first flare (median 9 semesters vs. 5 semesters; P = .02), he said.

There were no differences between groups in rates of hospitalization or surgery for Crohn’s disease, new fistula, or rescue treatment, defined as use of cyclosporine, experimental therapy, or surgery.

A review of the endoscopy reports suggested a trend for fewer large ulcers per patient in the top-down group than the step-up group, but this did not reach statistical significance (14% vs. 24%; P = .11), Dr. Hoekman said. The median proportion of endoscopies with remission also was similar (49% vs. 43%; P = .46).

Rates of adverse events also were similar in the top-down and step-up groups including infusion reactions (14% vs. 10%), serious infection (22% vs. 10%), malignancy (0 vs. 1 event), and dysplastic lesions (0 vs. 2 events), he said.

[email protected]

On Twitter@pwendl

WASHINGTON – More intensive treatment with early combined immunosuppression was associated with a longer time to first flare and fewer flares than conventional management during long-term follow-up of patients with Crohn’s disease.

Fewer patients treated with the “top-down” approach required anti–tumor necrosis factor (anti-TNF) agents or corticosteroids during follow-up, Dr. Daniël Hoekman reported during the annual Digestive Disease Week.

Current guidelines advocate an initial “step-up” approach for Crohn’s disease that focuses on controlling symptoms with corticosteroids followed by immunomodulators and then anti-TNF inhibitors to manage the chronic relapsing-remitting course of Crohn’s.

A new strategy has been proposed with the aim of altering the disease course and slow progression by reversing the treatment paradigm from a step-up to a top-down approach. A 2-year, randomized European trial showed that a top-down approach, combining early immunosuppression with infliximab (Remicade) and azathioprine (Imuran in Canada, Azasan in the United States) followed by azathioprine monotherapy and, if necessary, additional infliximab and corticosteroids, was more effective than step-up management for induction of remission and reduction of steroids in the short term (Lancet 2008;371:660-7).

To investigate the long-term outcome of Crohn’s disease, a retrospective chart review was performed in 119 of the 133 trial participants followed for 8 years or 16 semesters (mean 14.2 semesters) after the initial 2-year trial period. Management during the present study was left to physician discretion. At the start of the extended follow-up, most patients in both the step-up and top-down groups were on immunomodulators (66% vs. 82%) and only a small portion were using infliximab (15% vs. 20%). A total of 164 endoscopy reports were available for 59% of patients.

During follow-up, significantly more patients treated with the step-up approach than the top-down approach required anti-TNF inhibitors (73% vs. 54%; P = .04) and steroids (62% vs. 41%; P = .02), said Dr. Hoekman of the Academic Medical Center, Amsterdam.

There was no difference between the step-up and top-down groups in long-term remission rates (70% vs. 73%; P = .85).

The top-down group, however, had significantly fewer flares than the step-up group (7% vs. 19%; P = .01) and a longer time to first flare (median 9 semesters vs. 5 semesters; P = .02), he said.

There were no differences between groups in rates of hospitalization or surgery for Crohn’s disease, new fistula, or rescue treatment, defined as use of cyclosporine, experimental therapy, or surgery.

A review of the endoscopy reports suggested a trend for fewer large ulcers per patient in the top-down group than the step-up group, but this did not reach statistical significance (14% vs. 24%; P = .11), Dr. Hoekman said. The median proportion of endoscopies with remission also was similar (49% vs. 43%; P = .46).

Rates of adverse events also were similar in the top-down and step-up groups including infusion reactions (14% vs. 10%), serious infection (22% vs. 10%), malignancy (0 vs. 1 event), and dysplastic lesions (0 vs. 2 events), he said.

[email protected]

On Twitter@pwendl

WASHINGTON – Black patients with inflammatory bowel disease were significantly more likely to have at least one extraintestinal manifestation of the disease than were white patients, particularly uveitis, in a study of more than 500 people with Crohn’s disease or ulcerative colitis, Dr. Jemilat Badamas reported at the annual Digestive Disease Week.

Black patients were about twice as likely to have uveitis than were white patients in the study, after researchers controlled for other risk factors for extraintestinal manifestations of IBD, said Dr. Badamas, a gastroenterology fellow at Johns Hopkins University, Baltimore. Based on these results, and the increased rate of uveitis among black IBD patients seen in other studies, “practitioners should consider proactive referral of African-Americans [with IBD] to be screened for uveitis,” she said.

The study compared the incidence of various extraintestinal manifestations of IBD among 196 black patients and 342 white patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), which included uveitis, small and large joint disease, sacroiliitis, ankylosing spondylitis, episcleritis, pyoderma gangrenosum (PG), erythema nodosum (EN), and progressive sclerosing cholangitis, confirmed in the medical records. All the patients had been treated at outpatient gastroenterology clinics and infliximab infusion clinics at Johns Hopkins Hospital, including patients who were hospitalized and were subsequently followed up at the GI clinics. Cases with no information on extraintestinal manifestations were excluded.

Enrollment of all patients at one medical center overcame one of the limitations of previous studies evaluating racial differences in extraintestinal manifestations of IBD, where most of the black and white patients were treated in different centers, so researchers could not account for differences in practices at different institutions or access to subspecialty care, she pointed out.

In the Johns Hopkins study, patients in both groups were diagnosed with IBD at a mean age of 28-29 years. Among the black patients, 62% were female and they were enrolled in the study at a mean age of 38 years. Among the white patients, half were female and they were enrolled at a mean age of 41 years. The data on these patients are being collected as part of the Multicenter African American Inflammatory Bowel Disease Study (MAAIS).

More black patients (41%) had at least one extraintestinal manifestation of IBD compared with white patients (33%). The most common was large joint disease, affecting 25.5% of black patients and 19% of white patients, Dr. Badamas said. Uveitis was more common in black patients (6.9% vs. 2.7%), a difference that was statistically significant (P = 0.021). Pyoderma gangrenosum was more common in black patients (4.8% vs. 1.8%), a difference of borderline significance (P = 0.051).

After the researchers controlled for gender, disease location, and extent of disease, which are factors known to be associated with extraintestinal manifestations of IBD, there were no significant differences between the two groups for most of the manifestations, she said. But black patients were about two times more likely to have uveitis, compared with white patients (odds ratio, 2.3), and were 1.5 times more likely to have at least one extraintestinal manifestation (OR, 1.5), she added.

The study did not include a temporal analysis to determine if any of these manifestations occurred before the diagnosis of IBD was made, but Dr. Badamas said that most were diagnosed after the diagnosis of IBD.

Dr. Badamas had no relevant disclosures.

[email protected]

WASHINGTON – Black patients with inflammatory bowel disease were significantly more likely to have at least one extraintestinal manifestation of the disease than were white patients, particularly uveitis, in a study of more than 500 people with Crohn’s disease or ulcerative colitis, Dr. Jemilat Badamas reported at the annual Digestive Disease Week.

Black patients were about twice as likely to have uveitis than were white patients in the study, after researchers controlled for other risk factors for extraintestinal manifestations of IBD, said Dr. Badamas, a gastroenterology fellow at Johns Hopkins University, Baltimore. Based on these results, and the increased rate of uveitis among black IBD patients seen in other studies, “practitioners should consider proactive referral of African-Americans [with IBD] to be screened for uveitis,” she said.

The study compared the incidence of various extraintestinal manifestations of IBD among 196 black patients and 342 white patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), which included uveitis, small and large joint disease, sacroiliitis, ankylosing spondylitis, episcleritis, pyoderma gangrenosum (PG), erythema nodosum (EN), and progressive sclerosing cholangitis, confirmed in the medical records. All the patients had been treated at outpatient gastroenterology clinics and infliximab infusion clinics at Johns Hopkins Hospital, including patients who were hospitalized and were subsequently followed up at the GI clinics. Cases with no information on extraintestinal manifestations were excluded.

Enrollment of all patients at one medical center overcame one of the limitations of previous studies evaluating racial differences in extraintestinal manifestations of IBD, where most of the black and white patients were treated in different centers, so researchers could not account for differences in practices at different institutions or access to subspecialty care, she pointed out.

In the Johns Hopkins study, patients in both groups were diagnosed with IBD at a mean age of 28-29 years. Among the black patients, 62% were female and they were enrolled in the study at a mean age of 38 years. Among the white patients, half were female and they were enrolled at a mean age of 41 years. The data on these patients are being collected as part of the Multicenter African American Inflammatory Bowel Disease Study (MAAIS).

More black patients (41%) had at least one extraintestinal manifestation of IBD compared with white patients (33%). The most common was large joint disease, affecting 25.5% of black patients and 19% of white patients, Dr. Badamas said. Uveitis was more common in black patients (6.9% vs. 2.7%), a difference that was statistically significant (P = 0.021). Pyoderma gangrenosum was more common in black patients (4.8% vs. 1.8%), a difference of borderline significance (P = 0.051).

After the researchers controlled for gender, disease location, and extent of disease, which are factors known to be associated with extraintestinal manifestations of IBD, there were no significant differences between the two groups for most of the manifestations, she said. But black patients were about two times more likely to have uveitis, compared with white patients (odds ratio, 2.3), and were 1.5 times more likely to have at least one extraintestinal manifestation (OR, 1.5), she added.

The study did not include a temporal analysis to determine if any of these manifestations occurred before the diagnosis of IBD was made, but Dr. Badamas said that most were diagnosed after the diagnosis of IBD.

Dr. Badamas had no relevant disclosures.

[email protected]

WASHINGTON – Black patients with inflammatory bowel disease were significantly more likely to have at least one extraintestinal manifestation of the disease than were white patients, particularly uveitis, in a study of more than 500 people with Crohn’s disease or ulcerative colitis, Dr. Jemilat Badamas reported at the annual Digestive Disease Week.

Black patients were about twice as likely to have uveitis than were white patients in the study, after researchers controlled for other risk factors for extraintestinal manifestations of IBD, said Dr. Badamas, a gastroenterology fellow at Johns Hopkins University, Baltimore. Based on these results, and the increased rate of uveitis among black IBD patients seen in other studies, “practitioners should consider proactive referral of African-Americans [with IBD] to be screened for uveitis,” she said.

The study compared the incidence of various extraintestinal manifestations of IBD among 196 black patients and 342 white patients with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC), which included uveitis, small and large joint disease, sacroiliitis, ankylosing spondylitis, episcleritis, pyoderma gangrenosum (PG), erythema nodosum (EN), and progressive sclerosing cholangitis, confirmed in the medical records. All the patients had been treated at outpatient gastroenterology clinics and infliximab infusion clinics at Johns Hopkins Hospital, including patients who were hospitalized and were subsequently followed up at the GI clinics. Cases with no information on extraintestinal manifestations were excluded.

Enrollment of all patients at one medical center overcame one of the limitations of previous studies evaluating racial differences in extraintestinal manifestations of IBD, where most of the black and white patients were treated in different centers, so researchers could not account for differences in practices at different institutions or access to subspecialty care, she pointed out.

In the Johns Hopkins study, patients in both groups were diagnosed with IBD at a mean age of 28-29 years. Among the black patients, 62% were female and they were enrolled in the study at a mean age of 38 years. Among the white patients, half were female and they were enrolled at a mean age of 41 years. The data on these patients are being collected as part of the Multicenter African American Inflammatory Bowel Disease Study (MAAIS).

More black patients (41%) had at least one extraintestinal manifestation of IBD compared with white patients (33%). The most common was large joint disease, affecting 25.5% of black patients and 19% of white patients, Dr. Badamas said. Uveitis was more common in black patients (6.9% vs. 2.7%), a difference that was statistically significant (P = 0.021). Pyoderma gangrenosum was more common in black patients (4.8% vs. 1.8%), a difference of borderline significance (P = 0.051).

After the researchers controlled for gender, disease location, and extent of disease, which are factors known to be associated with extraintestinal manifestations of IBD, there were no significant differences between the two groups for most of the manifestations, she said. But black patients were about two times more likely to have uveitis, compared with white patients (odds ratio, 2.3), and were 1.5 times more likely to have at least one extraintestinal manifestation (OR, 1.5), she added.

The study did not include a temporal analysis to determine if any of these manifestations occurred before the diagnosis of IBD was made, but Dr. Badamas said that most were diagnosed after the diagnosis of IBD.

Dr. Badamas had no relevant disclosures.

[email protected]

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that she and her colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real-world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

Dr. Backus had no conflicts of interest.

[email protected]


On Twitter @pwendl

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that she and her colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real-world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

Dr. Backus had no conflicts of interest.

[email protected]


On Twitter @pwendl

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that she and her colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real-world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

Dr. Backus had no conflicts of interest.

[email protected]


On Twitter @pwendl

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.

Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that he and his colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.

Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that he and his colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.

Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that he and his colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.

Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that she and her* colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

[email protected]


On Twitter @pwendl

*This story was updated July 1, 2015

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.

Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that she and her* colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

[email protected]


On Twitter @pwendl

*This story was updated July 1, 2015

WASHINGTON – Sustained virologic response rates for genotype 1 and 2 patients are lower with sofosbuvir-based hepatitis C virus regimens in routine clinical practice than clinical trials, results from a large observational cohort analysis showed.

Patients with advanced liver disease and those with detectable HCV RNA at 4 weeks were significantly less likely to achieve a sustained virologic response (SVR), study author Dr. Lisa Backus reported at the annual Digestive Disease Week.

SVR rates with sofosbuvir (Sovaldi), which was approved in late 2013 for the treatment of HCV, have been reported in clinical trials generally in the 90%-plus range in genotype 1 (GT1) and 2 (GT2) patients.

“Often, however, it’s apparent that there are differences between the outcomes in clinical trials and routine medical practice,” said Dr. Backus of the VA Palo Alto (Calif.) Health Care System.

As a result, the investigators assessed clinical data from electronic medical records for 4,026 patients with GT1 or GT2 HCV who started sofosbuvir-based therapy for the recommended 12-week duration through the U.S. Department of Veterans Affairs, the largest integrated national provider of HCV care. Roughly a third of the patients were treatment experienced, and their average age was 61 years.

Among 3,203 GT1 patients, 1,302 started sofosbuvir, peginterferon, and ribavirin (SOF+PEG+RBV); 1,559, sofosbuvir plus simeprevir (SOF+SIM; Olysio); and 342, SOF+SIM+RBV. All 823 GT2 patients started SOF+RBV. About 10%-14% of patients did not receive 84 days of drug.

Patients were considered to have no SVR if HCV RNA was detectable on any test after the end of treatment, if they had no test after the end of treatment and HCV RNA was detectable on their last on-treatment test, or if they died before 12 weeks after the end of treatment. In all, 2,417 GT1 patients and 619 GT2 patients had SVR results.

Overall SVR rates were 66.8% with SOF+PEG+RBV, 75.3% with SOF+SIM, and 74.1% with SOF+SIM+RBV in GT1 patients and 79% with SOF+RBV in GT2 patients, Dr. Backus said.

For GT1 patients, SVR rates for treatment-naive vs. treatment-experienced patients were significantly different with SOF+PEG+RBV (73.7% vs. 55.6%; P <.001), but not with SOF+SIM (77.8% vs. 71.2%) or SOF+SIM+RBV (74.7% vs. 73.3%).

SVR rates were also different with SOF+RBV for GT2 treatment-naive vs. treatment-experienced patients (81.6% vs. 70.9%; P <.01), she reported.

Baseline factors associated with significantly lower SVR rates varied in GT1 treatment-naive and treatment-experienced patients by regimen, although an aspartate aminotransferase-to-platelet ratio index (APRI) score >2 was a significant predictor in treatment-naive patients for all three regimens and in treatment-experienced patients on SOF+PEG+RBV or SOF+SIM.

In a multivariate analysis adjusted for age, sex, race, body mass index (BMI), decompensated liver disease, diabetes, treatment experience, APRI score, HCV subtype, and regimen, GT1 patients with a BMI of at least 30 kg/m² had significantly lower odds of achieving a sustained virologic response (odds ratio, 0.64), as did those with decompensated liver disease (OR, 0.51), prior treatment experience (OR, 0.58), or an APRI score >2 (OR, 0.44), or those receiving SOF+PEG+RBV, compared with SOF-SIM (OR, 0.50; P values for all <.001), Dr. Backus said. The odds of achieving a sustained virologic response with SOF+SIM+RBV did not differ from the odds of doing so with SOF+SIM (OR, 1.03; P = .86).

Adding 4-week HCV RNA levels to the model did not change most baseline predictors, but showed that the odds of an SVR were reduced 41% for patients with 4-week HCV RNA <43 IU/mL (OR, 0.59; P <.001) and 58% for those with 4-week HCV RNA ≥43 IU/mL (OR, 0.42; P <.001), compared with patients with undetectable levels.

In GT2 patients, significant baseline predictors of lower SVR rates were an APRI >2 and a fibrosis-4 (FIB-4) index >3.25 in treatment-naive patients and a FIB-4 >3.25 in treatment-experienced patients.

Using the first multivariate model, treatment experience (OR, 0.55; P <.01) and an APRI >2 (OR, 0.39; P <.001) predicted markedly lower odds of a sustained virologic response. Both factors remained significant in the second multivariate model, along with 4-week HCV RNA <43 IU/mL (OR, 0.29; P <.001) and ≥43 IU/mL (OR, 0.21; P <.001), Dr. Backus reported.

Study limitations were the lack of treatment randomization, testing and follow-up at the discretion of the provider, the use of surrogate laboratory markers (APRI or FIB-4) since few patients had biopsy or fibroscan results, and the lack of data on Q80K polymorphism status, she said.

Attendees questioned whether compliance could have caused such vastly lower SVR rates than reported in other trial settings. Dr. Backus acknowledged that she and her* colleagues did not do chart reviews of actual discontinuation rates, but argued that adherence rates of 70%-80% in regular clinical practice in other fields of medicine, such as infectious diseases, are considered incredibly high.

“I think some of it is people have just gotten really spoiled, and we now think that 95% treatment completion is the real world,” she said. “We just don’t see it. I think one may argue that some of the other supposed real world trials, the TARGET or TRIO trials, those generally are people getting seen at academic medical centers. … Those kinds of centers, although they’re a version of the real world, it’s not quite the same as my nurse practitioner in some of the VA clinics.”

[email protected]


On Twitter @pwendl

*This story was updated July 1, 2015

WASHNGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton-pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton-pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. PPIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence.

In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%.

In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time. Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States.

The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHNGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton-pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton-pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. PPIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence.

In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%.

In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time. Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States.

The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHNGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton-pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton-pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen. PPIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence.

In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%.

In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time. Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States.

The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHINGTON – The anti-MAdCAM candidate, PF-00547659, induced responses in up to 54% of patients with moderately to severely active ulcerative colitis failing at least one prior therapy.

At the optimal dose of 22.5 mg, 16.7% of all patients and 25.8% of patients naive to anti–tumor necrosis factor (TNF) therapy achieved remission with the anti-mucosal addressin cell adhesion molecule 1 (MAdCAM-1) monoclonal antibody in the phase II TURANDOT trial, Dr. Walter Reinisch reported in a late-breaking abstract session at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

Selective blockade of adhesion molecules is an attractive treatment strategy for inflammatory bowel disease, with one approach shown to improve clinical outcomes by blocking alpha4beta7 integrin. Drugs that bind to alpha4beta7 include the ulcerative colitis (UC) drug vedolizumab (Entyvio), the experimental UC drug etrolizumab, and the Crohn’s disease and multiple sclerosis drug natalizumab (Tysabri).

Natalizumab, which also binds to alpha4beta1 integrin on endothelial cells expressing VCAM-1, however, has raised concerns because it increases the risk of progressive multifocal leukoencephalopathy (PML), a rare and fatal viral infection of the brain.

PF-00547659 has no cross-reactivity with vascular cell adhesion proten-1 (VCAM-1) and has no effect on central nervous system immune surveillance, said Dr. Reinisch of McMaster University, Hamilton, Ont.

The phase II double-blind TURANDOT trial randomly assigned 357 patients with moderate to severe UC who had failed or were intolerant to at least one conventional therapy to one of four doses of PF-00547659 (7.5 mg, 22.5 mg, 75 mg, or 225 mg) or placebo delivered by subcutaneous injection in three doses separated by 4 weeks. The primary endpoint was clinical remission, defined by a total Mayo Score at week 12 of ≤ 2 points with no individual subscore > 1. More than half of patients had received prior anti-TNF therapy, the average baseline total Mayo Score was 8.4, and average age was 40 years.

Clinical remission rates followed a bell-shaped curve, occurring in 2.7% of patients on placebo, 11.3% on PF-00547659 at the 7.5-mg dose, 16.7% at 22.5 mg, 15.5% at 75 mg, and 5.7% at 225 mg. The difference between placebo and active treatment was statistically significant at a P value of less than .05 for all but the 225-mg dose, Dr. Reinisch reported.

Clinical responses were seen in 28.8%, 38%, 54.2%, 45%, and 50% of patients, respectively, with the three highest PF-00547659 doses achieving significance (P values < .05).

Compared with placebo, mucosal healing was significantly more common at the 22.5-mgdose (8.2% vs. 27.8%; P < .05) and 75-mg dose (8.2% vs. 25.4%; P < .05) and trended higher for the 7.5-mg dose (15.5%) and 225-mg dose (14.3%).

Mucosal healing may be driving the bell-shaped dose-response curve, but additional analyses are ongoing to determine whether the curve is a robust finding, he said.

Fetal calprotectin declined in all treatment groups versus placebo, with the nadir reached at week 8 and maintained.

No major differences in safety signals between placebo and active treatment were seen, including infections (18% vs. 21%), GI infections (1% vs. 4%), and infections in ex-GI MAdCAM bearing tissues (7% vs. 6%), Dr. Reinisch said.

During a discussion of the findings, concerns were raised about a theoretical risk for PML akin to natalizumab because MAdCAM is not that specific. Dr. Reinisch repeated that there’s no evidence to suggest this, and cited a vedolizumab trial showing no PML in patients with Crohn’s disease (N. Engl. J. Med. 2013;369:711-21).

Dr. Reinisch disclosed ties with several drug companies, including Pfizer, which sponsored the study.

[email protected]

On Twitter @pwendl

WASHINGTON – The anti-MAdCAM candidate, PF-00547659, induced responses in up to 54% of patients with moderately to severely active ulcerative colitis failing at least one prior therapy.

At the optimal dose of 22.5 mg, 16.7% of all patients and 25.8% of patients naive to anti–tumor necrosis factor (TNF) therapy achieved remission with the anti-mucosal addressin cell adhesion molecule 1 (MAdCAM-1) monoclonal antibody in the phase II TURANDOT trial, Dr. Walter Reinisch reported in a late-breaking abstract session at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

Selective blockade of adhesion molecules is an attractive treatment strategy for inflammatory bowel disease, with one approach shown to improve clinical outcomes by blocking alpha4beta7 integrin. Drugs that bind to alpha4beta7 include the ulcerative colitis (UC) drug vedolizumab (Entyvio), the experimental UC drug etrolizumab, and the Crohn’s disease and multiple sclerosis drug natalizumab (Tysabri).

Natalizumab, which also binds to alpha4beta1 integrin on endothelial cells expressing VCAM-1, however, has raised concerns because it increases the risk of progressive multifocal leukoencephalopathy (PML), a rare and fatal viral infection of the brain.

PF-00547659 has no cross-reactivity with vascular cell adhesion proten-1 (VCAM-1) and has no effect on central nervous system immune surveillance, said Dr. Reinisch of McMaster University, Hamilton, Ont.

The phase II double-blind TURANDOT trial randomly assigned 357 patients with moderate to severe UC who had failed or were intolerant to at least one conventional therapy to one of four doses of PF-00547659 (7.5 mg, 22.5 mg, 75 mg, or 225 mg) or placebo delivered by subcutaneous injection in three doses separated by 4 weeks. The primary endpoint was clinical remission, defined by a total Mayo Score at week 12 of ≤ 2 points with no individual subscore > 1. More than half of patients had received prior anti-TNF therapy, the average baseline total Mayo Score was 8.4, and average age was 40 years.

Clinical remission rates followed a bell-shaped curve, occurring in 2.7% of patients on placebo, 11.3% on PF-00547659 at the 7.5-mg dose, 16.7% at 22.5 mg, 15.5% at 75 mg, and 5.7% at 225 mg. The difference between placebo and active treatment was statistically significant at a P value of less than .05 for all but the 225-mg dose, Dr. Reinisch reported.

Clinical responses were seen in 28.8%, 38%, 54.2%, 45%, and 50% of patients, respectively, with the three highest PF-00547659 doses achieving significance (P values < .05).

Compared with placebo, mucosal healing was significantly more common at the 22.5-mgdose (8.2% vs. 27.8%; P < .05) and 75-mg dose (8.2% vs. 25.4%; P < .05) and trended higher for the 7.5-mg dose (15.5%) and 225-mg dose (14.3%).

Mucosal healing may be driving the bell-shaped dose-response curve, but additional analyses are ongoing to determine whether the curve is a robust finding, he said.

Fetal calprotectin declined in all treatment groups versus placebo, with the nadir reached at week 8 and maintained.

No major differences in safety signals between placebo and active treatment were seen, including infections (18% vs. 21%), GI infections (1% vs. 4%), and infections in ex-GI MAdCAM bearing tissues (7% vs. 6%), Dr. Reinisch said.

During a discussion of the findings, concerns were raised about a theoretical risk for PML akin to natalizumab because MAdCAM is not that specific. Dr. Reinisch repeated that there’s no evidence to suggest this, and cited a vedolizumab trial showing no PML in patients with Crohn’s disease (N. Engl. J. Med. 2013;369:711-21).

Dr. Reinisch disclosed ties with several drug companies, including Pfizer, which sponsored the study.

[email protected]

On Twitter @pwendl

WASHINGTON – The anti-MAdCAM candidate, PF-00547659, induced responses in up to 54% of patients with moderately to severely active ulcerative colitis failing at least one prior therapy.

At the optimal dose of 22.5 mg, 16.7% of all patients and 25.8% of patients naive to anti–tumor necrosis factor (TNF) therapy achieved remission with the anti-mucosal addressin cell adhesion molecule 1 (MAdCAM-1) monoclonal antibody in the phase II TURANDOT trial, Dr. Walter Reinisch reported in a late-breaking abstract session at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

Selective blockade of adhesion molecules is an attractive treatment strategy for inflammatory bowel disease, with one approach shown to improve clinical outcomes by blocking alpha4beta7 integrin. Drugs that bind to alpha4beta7 include the ulcerative colitis (UC) drug vedolizumab (Entyvio), the experimental UC drug etrolizumab, and the Crohn’s disease and multiple sclerosis drug natalizumab (Tysabri).

Natalizumab, which also binds to alpha4beta1 integrin on endothelial cells expressing VCAM-1, however, has raised concerns because it increases the risk of progressive multifocal leukoencephalopathy (PML), a rare and fatal viral infection of the brain.

PF-00547659 has no cross-reactivity with vascular cell adhesion proten-1 (VCAM-1) and has no effect on central nervous system immune surveillance, said Dr. Reinisch of McMaster University, Hamilton, Ont.

The phase II double-blind TURANDOT trial randomly assigned 357 patients with moderate to severe UC who had failed or were intolerant to at least one conventional therapy to one of four doses of PF-00547659 (7.5 mg, 22.5 mg, 75 mg, or 225 mg) or placebo delivered by subcutaneous injection in three doses separated by 4 weeks. The primary endpoint was clinical remission, defined by a total Mayo Score at week 12 of ≤ 2 points with no individual subscore > 1. More than half of patients had received prior anti-TNF therapy, the average baseline total Mayo Score was 8.4, and average age was 40 years.

Clinical remission rates followed a bell-shaped curve, occurring in 2.7% of patients on placebo, 11.3% on PF-00547659 at the 7.5-mg dose, 16.7% at 22.5 mg, 15.5% at 75 mg, and 5.7% at 225 mg. The difference between placebo and active treatment was statistically significant at a P value of less than .05 for all but the 225-mg dose, Dr. Reinisch reported.

Clinical responses were seen in 28.8%, 38%, 54.2%, 45%, and 50% of patients, respectively, with the three highest PF-00547659 doses achieving significance (P values < .05).

Compared with placebo, mucosal healing was significantly more common at the 22.5-mgdose (8.2% vs. 27.8%; P < .05) and 75-mg dose (8.2% vs. 25.4%; P < .05) and trended higher for the 7.5-mg dose (15.5%) and 225-mg dose (14.3%).

Mucosal healing may be driving the bell-shaped dose-response curve, but additional analyses are ongoing to determine whether the curve is a robust finding, he said.

Fetal calprotectin declined in all treatment groups versus placebo, with the nadir reached at week 8 and maintained.

No major differences in safety signals between placebo and active treatment were seen, including infections (18% vs. 21%), GI infections (1% vs. 4%), and infections in ex-GI MAdCAM bearing tissues (7% vs. 6%), Dr. Reinisch said.

During a discussion of the findings, concerns were raised about a theoretical risk for PML akin to natalizumab because MAdCAM is not that specific. Dr. Reinisch repeated that there’s no evidence to suggest this, and cited a vedolizumab trial showing no PML in patients with Crohn’s disease (N. Engl. J. Med. 2013;369:711-21).

Dr. Reinisch disclosed ties with several drug companies, including Pfizer, which sponsored the study.

[email protected]

On Twitter @pwendl

WASHINGTON – Even wonder drugs have their limits: Aspirin use was associated with a significant reduction in the incidence of noncardiac gastric adenocarcinoma, but it had no effect on the incidence of esophageal adenocarcinomas, results of a cohort study suggest.

Among participants enrolled in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), any aspirin use was associated with a nearly 40% reduction in the incidence of noncardiac gastric adenocarcinoma, whereas the incidence of gastroesophageal adenocarcinoma was numerically but not significantly increased, reported Dr. Jigarkumar A. Patel of the Walter Reed National Military Medical Center in Bethesda, Md.

Ibuprofen, another nonsteroidal anti-inflammatory drug (NSAID), showed a trend toward reduction in the incidence of esophageal adenocarcinoma but did not reach statistical significance.

“The role for aspirin or any other NSAID in cancer prevention still offers hope across some of the other upper gastrointestinal tract malignancies,” Dr. Patel said at the annual Digestive Disease Week.

Mortality rates for esophageal and gastric adenocarcinomas are among the highest of common cancers, with 5-year survival of 18% and 28%, respectively. The incidence of esophageal cancer has risen in the past several decades, with adenocarcinoma in the distal esophagus accounting for most cases in the United States, he said.

A 2011 analysis of individual patient data from randomized controlled trials showed that 5 or more years of aspirin use was associated with significantly lower risk for death from gastrointestinal cancer among all adult age groups, Dr. Patel noted.

To see whether chemoprevention with aspirin or ibuprofen could reduce the incidence of esophageal and gastric cancers, Dr. Patel and his colleagues looked at data on the use of each drug, collected from 1993 through 2001, for 149,024 participants in the PLCO trial. The participants ranged from 55 to 74 years in age and were followed for a median of 12.4 years. The investigators collected data on the incidence of esophageal and gastric cancers for the cohort and created multivariate models to arrive at hazard ratios (HR) for each type of cancer.

There were 487 upper gastrointestinal tract malignancies, which the authors divided by diagnostic codes into either esophageal, cardioesophageal, or noncardiac gastric (i.e., in the distal stomach) adenocarcinomas. They did not include squamous cell malignancies in the analysis.

Any aspirin use was associated with a significant reduction in risk for incident noncardiac gastric adenocarcinoma (HR, 0.61; P = .001). Aspirin had no apparent effects, however, on either esophageal or cardioespohageal cancers.

The strongest effect was seen among participants who reported using aspirin less than once a day but more than once a week (HR, 0.47; P = .005).

As noted before, there was a nonsignificant trend toward a benefit for ibuprofen use against noncardiac adenocarcinomas but only for those who reported it using it daily; weekly or monthly ibuprofen use did not appear to be protective.

“The mixed data could be in part due to some limitations of having multiple confounding factors, such as having Barrett’s esophagus, having reflux disease, having H. pylori, or reverse causation, which is a factor when patients consider taking NSAIDS when counseled by their primary care doctors,” he said.

Dr. Patel said that their findings are similar to those seen in other large cohort studies. However, until the results of randomized, prospective trials of aspirin chemoprevention, such as the study of Aspirin and Esomeprazole Chemoprevention in Barrett’s Metaplasia (ASPECT) and the Aspirin in Reducing Events in the Elderly trial, (ASPREE) become available, prospective cohort studies for evidence of aspirin’s protective effects will have to be relied upon.

The study was supported by the National Cancer Institute. Dr. Patel reported no conflicts of interest.

WASHINGTON – Even wonder drugs have their limits: Aspirin use was associated with a significant reduction in the incidence of noncardiac gastric adenocarcinoma, but it had no effect on the incidence of esophageal adenocarcinomas, results of a cohort study suggest.

Among participants enrolled in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), any aspirin use was associated with a nearly 40% reduction in the incidence of noncardiac gastric adenocarcinoma, whereas the incidence of gastroesophageal adenocarcinoma was numerically but not significantly increased, reported Dr. Jigarkumar A. Patel of the Walter Reed National Military Medical Center in Bethesda, Md.

Ibuprofen, another nonsteroidal anti-inflammatory drug (NSAID), showed a trend toward reduction in the incidence of esophageal adenocarcinoma but did not reach statistical significance.

“The role for aspirin or any other NSAID in cancer prevention still offers hope across some of the other upper gastrointestinal tract malignancies,” Dr. Patel said at the annual Digestive Disease Week.

Mortality rates for esophageal and gastric adenocarcinomas are among the highest of common cancers, with 5-year survival of 18% and 28%, respectively. The incidence of esophageal cancer has risen in the past several decades, with adenocarcinoma in the distal esophagus accounting for most cases in the United States, he said.

A 2011 analysis of individual patient data from randomized controlled trials showed that 5 or more years of aspirin use was associated with significantly lower risk for death from gastrointestinal cancer among all adult age groups, Dr. Patel noted.

To see whether chemoprevention with aspirin or ibuprofen could reduce the incidence of esophageal and gastric cancers, Dr. Patel and his colleagues looked at data on the use of each drug, collected from 1993 through 2001, for 149,024 participants in the PLCO trial. The participants ranged from 55 to 74 years in age and were followed for a median of 12.4 years. The investigators collected data on the incidence of esophageal and gastric cancers for the cohort and created multivariate models to arrive at hazard ratios (HR) for each type of cancer.

There were 487 upper gastrointestinal tract malignancies, which the authors divided by diagnostic codes into either esophageal, cardioesophageal, or noncardiac gastric (i.e., in the distal stomach) adenocarcinomas. They did not include squamous cell malignancies in the analysis.

Any aspirin use was associated with a significant reduction in risk for incident noncardiac gastric adenocarcinoma (HR, 0.61; P = .001). Aspirin had no apparent effects, however, on either esophageal or cardioespohageal cancers.

The strongest effect was seen among participants who reported using aspirin less than once a day but more than once a week (HR, 0.47; P = .005).

As noted before, there was a nonsignificant trend toward a benefit for ibuprofen use against noncardiac adenocarcinomas but only for those who reported it using it daily; weekly or monthly ibuprofen use did not appear to be protective.

“The mixed data could be in part due to some limitations of having multiple confounding factors, such as having Barrett’s esophagus, having reflux disease, having H. pylori, or reverse causation, which is a factor when patients consider taking NSAIDS when counseled by their primary care doctors,” he said.

Dr. Patel said that their findings are similar to those seen in other large cohort studies. However, until the results of randomized, prospective trials of aspirin chemoprevention, such as the study of Aspirin and Esomeprazole Chemoprevention in Barrett’s Metaplasia (ASPECT) and the Aspirin in Reducing Events in the Elderly trial, (ASPREE) become available, prospective cohort studies for evidence of aspirin’s protective effects will have to be relied upon.

The study was supported by the National Cancer Institute. Dr. Patel reported no conflicts of interest.

WASHINGTON – Even wonder drugs have their limits: Aspirin use was associated with a significant reduction in the incidence of noncardiac gastric adenocarcinoma, but it had no effect on the incidence of esophageal adenocarcinomas, results of a cohort study suggest.

Among participants enrolled in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), any aspirin use was associated with a nearly 40% reduction in the incidence of noncardiac gastric adenocarcinoma, whereas the incidence of gastroesophageal adenocarcinoma was numerically but not significantly increased, reported Dr. Jigarkumar A. Patel of the Walter Reed National Military Medical Center in Bethesda, Md.

Ibuprofen, another nonsteroidal anti-inflammatory drug (NSAID), showed a trend toward reduction in the incidence of esophageal adenocarcinoma but did not reach statistical significance.

“The role for aspirin or any other NSAID in cancer prevention still offers hope across some of the other upper gastrointestinal tract malignancies,” Dr. Patel said at the annual Digestive Disease Week.

Mortality rates for esophageal and gastric adenocarcinomas are among the highest of common cancers, with 5-year survival of 18% and 28%, respectively. The incidence of esophageal cancer has risen in the past several decades, with adenocarcinoma in the distal esophagus accounting for most cases in the United States, he said.

A 2011 analysis of individual patient data from randomized controlled trials showed that 5 or more years of aspirin use was associated with significantly lower risk for death from gastrointestinal cancer among all adult age groups, Dr. Patel noted.

To see whether chemoprevention with aspirin or ibuprofen could reduce the incidence of esophageal and gastric cancers, Dr. Patel and his colleagues looked at data on the use of each drug, collected from 1993 through 2001, for 149,024 participants in the PLCO trial. The participants ranged from 55 to 74 years in age and were followed for a median of 12.4 years. The investigators collected data on the incidence of esophageal and gastric cancers for the cohort and created multivariate models to arrive at hazard ratios (HR) for each type of cancer.

There were 487 upper gastrointestinal tract malignancies, which the authors divided by diagnostic codes into either esophageal, cardioesophageal, or noncardiac gastric (i.e., in the distal stomach) adenocarcinomas. They did not include squamous cell malignancies in the analysis.

Any aspirin use was associated with a significant reduction in risk for incident noncardiac gastric adenocarcinoma (HR, 0.61; P = .001). Aspirin had no apparent effects, however, on either esophageal or cardioespohageal cancers.

The strongest effect was seen among participants who reported using aspirin less than once a day but more than once a week (HR, 0.47; P = .005).

As noted before, there was a nonsignificant trend toward a benefit for ibuprofen use against noncardiac adenocarcinomas but only for those who reported it using it daily; weekly or monthly ibuprofen use did not appear to be protective.

“The mixed data could be in part due to some limitations of having multiple confounding factors, such as having Barrett’s esophagus, having reflux disease, having H. pylori, or reverse causation, which is a factor when patients consider taking NSAIDS when counseled by their primary care doctors,” he said.

Dr. Patel said that their findings are similar to those seen in other large cohort studies. However, until the results of randomized, prospective trials of aspirin chemoprevention, such as the study of Aspirin and Esomeprazole Chemoprevention in Barrett’s Metaplasia (ASPECT) and the Aspirin in Reducing Events in the Elderly trial, (ASPREE) become available, prospective cohort studies for evidence of aspirin’s protective effects will have to be relied upon.

The study was supported by the National Cancer Institute. Dr. Patel reported no conflicts of interest.