DDW 2015

WASHINGTON – Reactivation of tuberculosis and hepatitis B virus infections after starting treatment with anti–tumor necrosis factor (TNF) therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease (IBD), Dr. Jason Hou reported at the annual Digestive Disease Week.

The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.

CDC/Dr. Erskine Palmer

Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”

Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.

They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years.

Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.

They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.

They identified 12 patients with codes related to hepatitis B after the treatment started; 2 had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation.

There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.

The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued, and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.

Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.

The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.”

Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said. Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.

[email protected]

WASHINGTON – Reactivation of tuberculosis and hepatitis B virus infections after starting treatment with anti–tumor necrosis factor (TNF) therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease (IBD), Dr. Jason Hou reported at the annual Digestive Disease Week.

The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.

CDC/Dr. Erskine Palmer

Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”

Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.

They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years.

Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.

They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.

They identified 12 patients with codes related to hepatitis B after the treatment started; 2 had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation.

There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.

The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued, and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.

Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.

The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.”

Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said. Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.

[email protected]

WASHINGTON – Reactivation of tuberculosis and hepatitis B virus infections after starting treatment with anti–tumor necrosis factor (TNF) therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease (IBD), Dr. Jason Hou reported at the annual Digestive Disease Week.

The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.

CDC/Dr. Erskine Palmer

Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”

Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.

They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years.

Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.

They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.

They identified 12 patients with codes related to hepatitis B after the treatment started; 2 had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation.

There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.

The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued, and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.

Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.

The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.”

Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said. Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.

[email protected]

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, researchers performed a retrospective chart review 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 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, researchers performed a retrospective chart review 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 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, researchers performed a retrospective chart review 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 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 – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.

Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.

“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”

Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.

The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.

Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.

At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.

From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).

Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.

During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.

After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.

Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.

The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.

“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”

The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.

WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.

Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.

“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”

Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.

The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.

Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.

At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.

From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).

Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.

During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.

After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.

Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.

The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.

“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”

The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.

WASHINGTON – Treatment with an oral formulation of budesonide was associated with significant improvements in dysphagia and esophageal eosinophil counts in adolescents and adults with eosinophilic esophagitis, in a study that is also the first to use a recently validated scoring instrument to evaluate medical therapy for this disorder in a randomized trial.

Results of the multicenter, double-blind, randomized study comparing treatment with an oral budesonide suspension to placebo for 12 weeks in almost 100 patients with eosinophilic esophagitis (EoE) were reported in two separate presentations at the annual Digestive Disease Week. One of the investigators, Dr. Evan Dellon of the Center for Gastrointestinal Biology and Disease, at the University of North Carolina, Chapel Hill, said that treatment with this “mucoadherent” formulation of the topical steroid was associated with significant improvements in dysphagia symptoms, as measured with the Dysphagia Symptom Questionnaire (DSQ), and a histologic response rate of 39%, vs. 3% among those on placebo.

“The study not only adds to the evidence that topical budesonide is effective for inducing histologic response in subjects with active EoE, but [also] shows for the first time that symptoms of dysphagia, as measured with a validated symptom instrument, improve concordantly with the histologic and endoscopic findings,” Dr. Dellon said in an interview after the meeting. “Moreover, this study shows that a topical steroid formulation designed specifically for EoE, rather than an asthma formulation that is adapted for esophageal use, will likely be a beneficial and potentially preferred clinical treatment option.”

Another study investigator, Dr. Ikuo Hirano, professor of medicine and director of the gastroenterology and hepatology fellowship program at Northwestern University, Chicago, reported that treatment was also associated with significant improvements in the EoE Endoscopic Reference Score, EREFS, which was designed to classify and grade the severity of five major endoscopic features of EoE: edema, rings, exudates, furrows, and stricture formation. This was the first study to use this validated endoscopic scoring instrument in a randomized controlled trial of a medical therapy in patients with EoE, he said at the meeting.

The study was conducted between 2012 and 2014 at 25 U.S. sites, in patients aged 11-40 years with EoE. Baseline demographic and endoscopic characteristics were similar in the two groups. Their mean age was 21-22 years (41% of those on placebo and 35% of those on budesonide were younger than age 18 years) and 69% were male; most patients had edema, all had dysphagia, and 39%-41% had heartburn. Patients were excluded if they had esophageal stricture on screening endoscopy that did not allow passage of a standard adult diagnostic endoscope.

Patients were randomized to treatment with budesonide suspension, at a dose of 2 mg twice a day (51 patients) or a placebo suspension (42 patients). The primary outcomes were a change in the DSQ score from baseline, and the proportion of patients with a histologic response, defined as at least 6 eosinophils per high-power field (eos/hpf) from all biopsies. The final analysis included 87 patients.

At baseline, the mean peak eosinophil counts were 156/hpf among those on budesonide and 130/hpf among those on placebo; after treatment, the mean peak counts dropped to 39/hpf among those on budesonide (a 65% reduction) and to 113/hpf among those on placebo (a 10% reduction), a statistically significant difference (P < .05), said Dr. Dellon, also with the department of medicine at UNC.

From a mean of about 29 in both groups at baseline, DSQ scores dropped by a mean of 14.3 among the treated patients, vs. 7.5 among those on placebo, which was a statistically significant difference (P = .0096). The other primary endpoint, the histologic response rate, was 39% among treated patients, vs. 3% among those on placebo, also a significant difference (P < .0001).

Adverse events were not different between the two groups, and growth velocity among those under age 18 years and cortisol levels were not different between the two groups, he added. There was one case of esophageal candidiasis in a patient on budesonide.

During his presentation, Dr. Hirano said that there were also significant improvements in EREFS scores from baseline in the proximal and distal esophagus among those treated with budesonide, but not among those on placebo. Based on EREFS scores, oral budesonide “resulted in significant improvement in endoscopic features of edema, exudate, rings, [and] furrows, compared to placebo,” but there was no significant change in strictures, another component of the EREFS, in either the treatment or placebo groups. However, patients with high-grade strictures were not enrolled in the study, he added.

After treatment, proximal, distal, and total EREFS scores correlated with peak eosinophil counts, a highly statistically significant finding.

Dr. Hirano said that the primary endpoints used in most EoE clinical trials to date have focused mostly on assessments of symptoms and histopathology, which have limitations. “Symptoms are difficult to quantify and often intermittent [and] they may improve as a result of changes in eating behavior and food avoidance,” he said. Patient-reported outcome instruments have been recently validated, “but have questionable utility in clinical practice” and histology “has shown limited correlation between degree of esophageal eosinophilia and symptom severity [and does not] assess for modeling, an important determinant of overall disease complications,” he added.

The utility of endoscopy in EoE includes the features that are present in vast majority of patients with EoE, and provides a gross assessment of overall disease activity, “both in terms of inflammatory and fibrostenotic features,” he said.

“Endoscopic outcomes are now emerging as clinically relevant endpoints of therapy of trials of eosinophilic esophagitis that supports and complements” symptom and histologic assessments, Dr. Hirano commented, adding that more studies are need to determine the “relative importance of these individual endoscopic features as well as the appropriate utilization of endoscopic parameters in disease management.”

The study was funded by Meritage Pharma, recently acquired by the Shire group of companies. All authors received research funds to conduct the study, and Dr. Hirano disclosed having worked as a consultant for Meritage. Dr. Dellon’s disclosures included receiving grant and research support from Meritage. Shire is developing the oral budesonide suspension formulation as a treatment for adolescents and adults with EoE.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

WASHINGTON – An investigational once-daily antiviral drug combination produced high rates of sustained viral responses after 12 or 16 weeks of therapy – with or without ribavirin – in patients with chronic hepatitis viral infections for whom prior therapy with peg-interferon and ribavirin had failed, investigators reported.

The rate of sustained viral responses at 12 weeks after the end of treatment (SVR12) was 92% for patients who received the combination of grazoprevir and elbasvir (GZR/EBR, Merck) alone, compared with 94% for patients who received the antivirals plus ribavirin, reported Dr. Paul Kwo of Indiana University Hospital in Indianapolis.

Among patients who received 16 weeks of therapy, the SVR12 rates were 92% without ribavirin, and 97% with ribavirin, Dr. Kwo said at the annual Digestive Disease Week.

“In patients who have failed peg-interferon and ribavirin therapy, 12 weeks of grazoprevir and elbasvir without ribavirin gives outstanding SVR rates in genotype 1b-infected individuals, regardless of treatment response, including those with cirrhosis. If you’re a relapser with genotype 1a or genotype 4 infection, 12 weeks of grazoprevir and elbasvir gives outstanding SVR rates. For genotype 1a, 4 and 6 prior null and partial responders, including those with cirrhosis, 16 weeks of grazoprevir and elbasvir with ribavirin gives outstanding SVR rates with no virologic failures,” he said.

Dr. Kwo presented updated results from the C-EDGE(Study of Efficacy and Safety of Grazoprevir (MK-5172)/Elbasvir (MK-8742) Combination Regimen for Treatment-Naive Participants With Chronic Hepatitis C Virus Genotypes 1, 4, and 6) treatment-experienced trial.

The 12-week C-EDGE results in 316 treatment-naive patients were presented earlier this year in Vienna at the International Liver Congress.

The fixed-dose, once-daily combination is composed of grazoprevir, an inhibitor of the HCV NS3/4a protease, at a dose of 100 mg, and elbasvir, a potent inhibitor of the NS5a protein, at a dose of 50 mg. This combination was shown to have broad activity against most HCV genotypes in vitro, and was efficacious in both treatment-naive and treatment-experienced patients with and without cirrhosis, including those with HIV/HCV coinfections, in the C-WORTHY trial.

The C-EDGE study was a phase III trial of GZR/EBR with or without ribavirin for 12 or 16 weeks for patients for whom prior therapy with peg-interferon and ribavirin had failed because of either null or partial response or viral relapse. The trial included patients with and without cirrhosis, those with HCV genotypes 1, 4, or 6, and those with either HCV mono-infections or HIV coinfections.

A total of 420 patients were enrolled.

As noted before, 97 of 105 patients (92%) on 12 weeks of therapy without ribavirin had an SVR12, although two patients in this group were lost to follow-up or discontinued therapy for reasons other than virologic failure (included as nonresponders). Among patients who received 12 weeks of GZR/EBR plus ribavirin, 98 of 104 (94%) had an SVR12, with no losses to follow-up.

For those patients treated for 16 weeks, 97 of 105 (92%) without ribavirin had an SVR12, compared with 103 of 106 (97%) who received ribavirin in addition to the combination antivirals. In these groups, one and three patients, respectively, were lost to follow-up.

In a subanalysis by HCV genotype or subtype, the combination alone was least effective among patients with genotype 4 treated for 16 weeks, with 3 of 5 patients (60%) having an SVR12, compared with 7 of 9 patients (79%) with genotype 4 treated with no ribavirin for 12 weeks, 14 of 15 (93%) with ribavirin for 12 weeks, and 8 of 8 (100%) treated with ribavirin for 16 weeks. The overall numbers of patients in each subgroup was too small for statistical significance analysis, however.

Among patients with HCV coinfection, the SVR12 rate was 100% in all treatment arms except 16 weeks GZR/EBR without ribavirin (5 of 6; 83%).

A subanalysis by prior response, excluding the 12 total patients who did not complete treatment, showed excellent SVR12 rates in all four treatment arms among patients with a prior relapse, and slightly less robust but still high rates among prior partial or null responders, Dr. Kwo said.

Patients tolerated the regimen well, with the rates of serious adverse events ranging from 2.9% to 3.8%. There were no deaths, and seven discontinuations due to adverse events (one in each in the 12-week arms, and five in the 16-week with ribavirin arm). A total of 31 patients who received ribavirin had hemoglobin reductions below 10 g/dL, and 60 reported fatigue, both common with ribavirin. The majority of adverse events in all arms were fatigue, headache, and nausea.

The combination has received two Breakthrough Therapy designations from the Food and Drug Administration for patients with HCV genotype 4, and for patients with genotype 1 infections who are on hemodialysis for end stage renal disease. The breakthrough designation makes the drug eligible for expedited review.

Dr. Kwo disclosed ties with Merck, which supported the C-EDGE study.

Achieving a cure in hepatitis C infection could result in significant economic gains, with a study estimating that the beneficial effects in terms of improved worker productivity could total around $3.23 billion per year for the United States alone.

Researchers used data on work productivity and activity scores from patients enrolled in clinical trials of the all-oral sofosbuvir and lepidasvir combo to estimate the impact of achieving sustained virologic response at 12 weeks (SVR-12) on workers’ productivity.

They calculated an average work productivity loss of $4,954 for each employed patient with chronic hepatitis C infection per year in the United States and $1,129 per year for the five European Union countries included in the mix.“These new all-oral combinations such as lepidasvir and sofosbuvir have cure rates between 95% and 99% with minimum side effects, [so] treating patients with these combinations results in improved work productivity, improved quality of life, and patient-reported outcomes that can translate into economic benefit,” Dr. Zobair M. Younossi of the Inova Fairfax Medical Campus, Falls Church, Va., said at the annual Digestive Disease Week.

No conflicts of interest were disclosed.

Achieving a cure in hepatitis C infection could result in significant economic gains, with a study estimating that the beneficial effects in terms of improved worker productivity could total around $3.23 billion per year for the United States alone.

Researchers used data on work productivity and activity scores from patients enrolled in clinical trials of the all-oral sofosbuvir and lepidasvir combo to estimate the impact of achieving sustained virologic response at 12 weeks (SVR-12) on workers’ productivity.

They calculated an average work productivity loss of $4,954 for each employed patient with chronic hepatitis C infection per year in the United States and $1,129 per year for the five European Union countries included in the mix.“These new all-oral combinations such as lepidasvir and sofosbuvir have cure rates between 95% and 99% with minimum side effects, [so] treating patients with these combinations results in improved work productivity, improved quality of life, and patient-reported outcomes that can translate into economic benefit,” Dr. Zobair M. Younossi of the Inova Fairfax Medical Campus, Falls Church, Va., said at the annual Digestive Disease Week.

No conflicts of interest were disclosed.

Achieving a cure in hepatitis C infection could result in significant economic gains, with a study estimating that the beneficial effects in terms of improved worker productivity could total around $3.23 billion per year for the United States alone.

Researchers used data on work productivity and activity scores from patients enrolled in clinical trials of the all-oral sofosbuvir and lepidasvir combo to estimate the impact of achieving sustained virologic response at 12 weeks (SVR-12) on workers’ productivity.

They calculated an average work productivity loss of $4,954 for each employed patient with chronic hepatitis C infection per year in the United States and $1,129 per year for the five European Union countries included in the mix.“These new all-oral combinations such as lepidasvir and sofosbuvir have cure rates between 95% and 99% with minimum side effects, [so] treating patients with these combinations results in improved work productivity, improved quality of life, and patient-reported outcomes that can translate into economic benefit,” Dr. Zobair M. Younossi of the Inova Fairfax Medical Campus, Falls Church, Va., said at the annual Digestive Disease Week.

No conflicts of interest were disclosed.