From the AGA Journals

Maintenance treatment with infliximab beyond 1 year after ileocolonic resection for Crohn’s disease was associated with reduced recurrence in a prospective, open-label long-term follow-up study.

Subjects were randomized in a prior study to receive infliximab for 1 year after ileocolonic resection performed between 2004 and 2007. At 1 year, the patients – who were blinded as to whether they had received placebo or infliximab – underwent ileocolonoscopy, were informed of the endoscopic findings, and were offered open-label infliximab every 8 weeks or other treatment.

Source: American Gastroenterological Association

Of 11 patients who had been receiving infliximab during the first year after surgery, 8 elected to stop infliximab, and all 8 experienced endoscopic recurrences at a mean of 18.2 months, including 5 who underwent re-resection. Of the three who continued on infliximab, one experienced endoscopic recurrence at the end of the first year, but stayed on treatment for control of arthritis symptoms and has not had Crohn’s disease symptoms, and two continued infliximab for the duration of long-term follow-up and remained in remission, Dr. Miguel Regueiro of the University of Pittsburgh Medical Center and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.12.035]).

Of 13 patients who received placebo during the first year after resection, 12 elected to initiate infliximab at 1-year follow-up, and 7 of those responded with endoscopic remission. The remaining five required another surgical resection. The patient who did not initiate infliximab ultimately progressed and underwent re-resection, the investigators said.

Overall, the time to first endoscopic recurrence was longer among those originally assigned to infliximab than among those who received placebo (1,231 days vs. 460 days). Additionally, 77.8% of colonoscopies performed on patients who received infliximab identified disease in remission, compared with only 6.1% of colonoscopies performed in patients not receiving biologic therapy.

"This analysis reflects the intermittent nature of use of infliximab and strong temporal relationship between exposure to infliximab and the probability of being in disease remission. To illustrate, compared with those not on biologic therapy, the adjusted rate ratio of patients being in remission while on infliximab was 13.47," they explained.

Also, while the rate of re-resectional surgery was similar among patients who originally received placebo and those who originally received infliximab, the time to repeat surgery was longer for those who originally received infliximab (1,798 vs. 1,058 days), and four of the five infliximab-treated patients who underwent reoperation during long-term follow-up did so after discontinuing infliximab after the initial 12 months, four of six of those without reoperation remained on infliximab for all or nearly all of the follow-up period, and five of seven patients who initially received placebo and who did not undergo reoperation received infliximab for most of the post 1-year follow-up period.

"Among patients on infliximab therapy for at least 60% of the full study period, and irrespective of initial random assignment, the rate of surgical re-resection was significantly lower, compared with those with less frequent use of infliximab (20.0% vs. 64.3%)," the investigators wrote.

The study is limited by several factors, including the small sample size and open-label design, and the fact that stopping and starting therapy was allowed at the discretion of the patient’s physician, with no restrictions placed on the use of concomitant medications.

The findings suggest, however, that patients at high risk for postoperative Crohn’s disease recurrence may benefit from long-term anti-TNF maintenance, the investigators concluded, noting that "results from postoperative anti-TNF studies with larger sample size and randomization to immediate ‘top down’ treatment vs. waiting for endoscopic recurrence are anticipated," they said.

Dr. Regueiro reported serving as a consultant for AbbVie, Janssen, Shire, Takeda, and UCB.

Maintenance treatment with infliximab beyond 1 year after ileocolonic resection for Crohn’s disease was associated with reduced recurrence in a prospective, open-label long-term follow-up study.

Subjects were randomized in a prior study to receive infliximab for 1 year after ileocolonic resection performed between 2004 and 2007. At 1 year, the patients – who were blinded as to whether they had received placebo or infliximab – underwent ileocolonoscopy, were informed of the endoscopic findings, and were offered open-label infliximab every 8 weeks or other treatment.

Source: American Gastroenterological Association

Of 11 patients who had been receiving infliximab during the first year after surgery, 8 elected to stop infliximab, and all 8 experienced endoscopic recurrences at a mean of 18.2 months, including 5 who underwent re-resection. Of the three who continued on infliximab, one experienced endoscopic recurrence at the end of the first year, but stayed on treatment for control of arthritis symptoms and has not had Crohn’s disease symptoms, and two continued infliximab for the duration of long-term follow-up and remained in remission, Dr. Miguel Regueiro of the University of Pittsburgh Medical Center and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.12.035]).

Of 13 patients who received placebo during the first year after resection, 12 elected to initiate infliximab at 1-year follow-up, and 7 of those responded with endoscopic remission. The remaining five required another surgical resection. The patient who did not initiate infliximab ultimately progressed and underwent re-resection, the investigators said.

Overall, the time to first endoscopic recurrence was longer among those originally assigned to infliximab than among those who received placebo (1,231 days vs. 460 days). Additionally, 77.8% of colonoscopies performed on patients who received infliximab identified disease in remission, compared with only 6.1% of colonoscopies performed in patients not receiving biologic therapy.

"This analysis reflects the intermittent nature of use of infliximab and strong temporal relationship between exposure to infliximab and the probability of being in disease remission. To illustrate, compared with those not on biologic therapy, the adjusted rate ratio of patients being in remission while on infliximab was 13.47," they explained.

Also, while the rate of re-resectional surgery was similar among patients who originally received placebo and those who originally received infliximab, the time to repeat surgery was longer for those who originally received infliximab (1,798 vs. 1,058 days), and four of the five infliximab-treated patients who underwent reoperation during long-term follow-up did so after discontinuing infliximab after the initial 12 months, four of six of those without reoperation remained on infliximab for all or nearly all of the follow-up period, and five of seven patients who initially received placebo and who did not undergo reoperation received infliximab for most of the post 1-year follow-up period.

"Among patients on infliximab therapy for at least 60% of the full study period, and irrespective of initial random assignment, the rate of surgical re-resection was significantly lower, compared with those with less frequent use of infliximab (20.0% vs. 64.3%)," the investigators wrote.

The study is limited by several factors, including the small sample size and open-label design, and the fact that stopping and starting therapy was allowed at the discretion of the patient’s physician, with no restrictions placed on the use of concomitant medications.

The findings suggest, however, that patients at high risk for postoperative Crohn’s disease recurrence may benefit from long-term anti-TNF maintenance, the investigators concluded, noting that "results from postoperative anti-TNF studies with larger sample size and randomization to immediate ‘top down’ treatment vs. waiting for endoscopic recurrence are anticipated," they said.

Dr. Regueiro reported serving as a consultant for AbbVie, Janssen, Shire, Takeda, and UCB.

Maintenance treatment with infliximab beyond 1 year after ileocolonic resection for Crohn’s disease was associated with reduced recurrence in a prospective, open-label long-term follow-up study.

Subjects were randomized in a prior study to receive infliximab for 1 year after ileocolonic resection performed between 2004 and 2007. At 1 year, the patients – who were blinded as to whether they had received placebo or infliximab – underwent ileocolonoscopy, were informed of the endoscopic findings, and were offered open-label infliximab every 8 weeks or other treatment.

Source: American Gastroenterological Association

Of 11 patients who had been receiving infliximab during the first year after surgery, 8 elected to stop infliximab, and all 8 experienced endoscopic recurrences at a mean of 18.2 months, including 5 who underwent re-resection. Of the three who continued on infliximab, one experienced endoscopic recurrence at the end of the first year, but stayed on treatment for control of arthritis symptoms and has not had Crohn’s disease symptoms, and two continued infliximab for the duration of long-term follow-up and remained in remission, Dr. Miguel Regueiro of the University of Pittsburgh Medical Center and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.12.035]).

Of 13 patients who received placebo during the first year after resection, 12 elected to initiate infliximab at 1-year follow-up, and 7 of those responded with endoscopic remission. The remaining five required another surgical resection. The patient who did not initiate infliximab ultimately progressed and underwent re-resection, the investigators said.

Overall, the time to first endoscopic recurrence was longer among those originally assigned to infliximab than among those who received placebo (1,231 days vs. 460 days). Additionally, 77.8% of colonoscopies performed on patients who received infliximab identified disease in remission, compared with only 6.1% of colonoscopies performed in patients not receiving biologic therapy.

"This analysis reflects the intermittent nature of use of infliximab and strong temporal relationship between exposure to infliximab and the probability of being in disease remission. To illustrate, compared with those not on biologic therapy, the adjusted rate ratio of patients being in remission while on infliximab was 13.47," they explained.

Also, while the rate of re-resectional surgery was similar among patients who originally received placebo and those who originally received infliximab, the time to repeat surgery was longer for those who originally received infliximab (1,798 vs. 1,058 days), and four of the five infliximab-treated patients who underwent reoperation during long-term follow-up did so after discontinuing infliximab after the initial 12 months, four of six of those without reoperation remained on infliximab for all or nearly all of the follow-up period, and five of seven patients who initially received placebo and who did not undergo reoperation received infliximab for most of the post 1-year follow-up period.

"Among patients on infliximab therapy for at least 60% of the full study period, and irrespective of initial random assignment, the rate of surgical re-resection was significantly lower, compared with those with less frequent use of infliximab (20.0% vs. 64.3%)," the investigators wrote.

The study is limited by several factors, including the small sample size and open-label design, and the fact that stopping and starting therapy was allowed at the discretion of the patient’s physician, with no restrictions placed on the use of concomitant medications.

The findings suggest, however, that patients at high risk for postoperative Crohn’s disease recurrence may benefit from long-term anti-TNF maintenance, the investigators concluded, noting that "results from postoperative anti-TNF studies with larger sample size and randomization to immediate ‘top down’ treatment vs. waiting for endoscopic recurrence are anticipated," they said.

Dr. Regueiro reported serving as a consultant for AbbVie, Janssen, Shire, Takeda, and UCB.

Two interferon-free combination therapies yielded sustained virologic responses of 96%-100% in an international, open-label, phase III, randomized trial involving 186 patients with refractory hepatitis C virus type 1b infection, Dr. Pietro Andreone and his colleagues reported in the August 2014 issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

Twelve weeks of treatment using the combination regimen plus ribavirin (91 patients) or the same regimen without ribavirin (95 patients) produced sustained virologic responses (SVRs) that were noninferior to historic SVRs reported in the literature for comparable patients treated with telaprevir plus pegylated-interferon plus ribavirin.

Source: American Gastroenterological Institute

None of the patients taking the new combination regimen experienced virologic failure while taking the drugs or relapse during the year after completing treatment. And adverse effects were characterized as "generally mild and manageable," said Dr. Andreone of the department of medical science and surgery, University of Bologna (Italy), and his associates.

HCV type 1b is the most prevalent genotype worldwide. Patients with this genotype who have failed on standard treatments "have not been extensively studied with currently approved or investigational interferon-free regimens, hence this large patient population represents a group with unmet need," the investigators noted.

They assessed such patients at 43 medical centers in Austria, Belgium, Italy, the Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Turkey, and the United States. All were aged between 18 and 70 years, and all were free of cirrhosis and coinfections.

The daily oral combination regimen consisted of ABT-450, a protease inhibitor that has shown in-vitro antiviral activity; ritonavir, a CYP3A4 inhibitor that enables once-daily rather than more frequent dosing of the ABT-450; ombitasvir, an HCV NS5A inhibitor; and dasabuvir, an HCV NS5B RNA nonnucleoside polymerase inhibitor.

The primary efficacy endpoint was an SVR rate noninferior to the historical rate for interferon-containing regimens in comparable patients. In the intention-to-treat analysis, the SVRs met and surpassed that standard, at 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.

Moreover, of the three patients who did not achieve a sustained virologic response, two had discontinued the study drug because of adverse events and one was lost to follow-up after only 4 weeks of treatment.

The most common adverse events were fatigue, headache, and nausea, all of which were significantly more frequent among patients taking ribavirin. Insomnia, anemia, rash, and elevated bilirubin also were related to ribavirin and were easily managed.

Only two patients discontinued treatment due to adverse events, neither of which were considered to be related to a study drug. One patient developed pancreatitis and another developed anxiety, tachycardia, and dyspnea.

Three other serious adverse events – cellulitis, nephrolithiasis, and osteoarthritis – also were judged to be unrelated to the study treatments.

Declines in hemoglobin levels occurred in 42% of the patients who received ribavirin but only 5.5% of those who did not. However, clinically significant declines occurred in only two patients, and neither of them required transfusions or erythropoietin.

Their findings show that 12 weeks of combined oral ABT-450/ritonavir/ombitasvir/dasabuvir therapy without ribavirin is at least as effective as interferon-containing regimens, and it produces significantly fewer and less severe adverse effects, the investigators said.

This study was somewhat limited in that it used an open-label design and did not include patients with concomitant cirrhosis, hepatitis B viral infection, or HIV infection, they added.

This study was sponsored by AbbVie, which also participated in the study design, data collection and analysis, and manuscript preparation. Dr. Andreone reported receiving research support from, being a consultant for, or serving on advisory committees for Roche, Merck, Gilead Sciences, Janssen Cilag, AbbVie, Boehringer Ingelheim, and BMS; his associates reported ties to numerous industry sources.

Two interferon-free combination therapies yielded sustained virologic responses of 96%-100% in an international, open-label, phase III, randomized trial involving 186 patients with refractory hepatitis C virus type 1b infection, Dr. Pietro Andreone and his colleagues reported in the August 2014 issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

Twelve weeks of treatment using the combination regimen plus ribavirin (91 patients) or the same regimen without ribavirin (95 patients) produced sustained virologic responses (SVRs) that were noninferior to historic SVRs reported in the literature for comparable patients treated with telaprevir plus pegylated-interferon plus ribavirin.

Source: American Gastroenterological Institute

None of the patients taking the new combination regimen experienced virologic failure while taking the drugs or relapse during the year after completing treatment. And adverse effects were characterized as "generally mild and manageable," said Dr. Andreone of the department of medical science and surgery, University of Bologna (Italy), and his associates.

HCV type 1b is the most prevalent genotype worldwide. Patients with this genotype who have failed on standard treatments "have not been extensively studied with currently approved or investigational interferon-free regimens, hence this large patient population represents a group with unmet need," the investigators noted.

They assessed such patients at 43 medical centers in Austria, Belgium, Italy, the Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Turkey, and the United States. All were aged between 18 and 70 years, and all were free of cirrhosis and coinfections.

The daily oral combination regimen consisted of ABT-450, a protease inhibitor that has shown in-vitro antiviral activity; ritonavir, a CYP3A4 inhibitor that enables once-daily rather than more frequent dosing of the ABT-450; ombitasvir, an HCV NS5A inhibitor; and dasabuvir, an HCV NS5B RNA nonnucleoside polymerase inhibitor.

The primary efficacy endpoint was an SVR rate noninferior to the historical rate for interferon-containing regimens in comparable patients. In the intention-to-treat analysis, the SVRs met and surpassed that standard, at 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.

Moreover, of the three patients who did not achieve a sustained virologic response, two had discontinued the study drug because of adverse events and one was lost to follow-up after only 4 weeks of treatment.

The most common adverse events were fatigue, headache, and nausea, all of which were significantly more frequent among patients taking ribavirin. Insomnia, anemia, rash, and elevated bilirubin also were related to ribavirin and were easily managed.

Only two patients discontinued treatment due to adverse events, neither of which were considered to be related to a study drug. One patient developed pancreatitis and another developed anxiety, tachycardia, and dyspnea.

Three other serious adverse events – cellulitis, nephrolithiasis, and osteoarthritis – also were judged to be unrelated to the study treatments.

Declines in hemoglobin levels occurred in 42% of the patients who received ribavirin but only 5.5% of those who did not. However, clinically significant declines occurred in only two patients, and neither of them required transfusions or erythropoietin.

Their findings show that 12 weeks of combined oral ABT-450/ritonavir/ombitasvir/dasabuvir therapy without ribavirin is at least as effective as interferon-containing regimens, and it produces significantly fewer and less severe adverse effects, the investigators said.

This study was somewhat limited in that it used an open-label design and did not include patients with concomitant cirrhosis, hepatitis B viral infection, or HIV infection, they added.

This study was sponsored by AbbVie, which also participated in the study design, data collection and analysis, and manuscript preparation. Dr. Andreone reported receiving research support from, being a consultant for, or serving on advisory committees for Roche, Merck, Gilead Sciences, Janssen Cilag, AbbVie, Boehringer Ingelheim, and BMS; his associates reported ties to numerous industry sources.

Two interferon-free combination therapies yielded sustained virologic responses of 96%-100% in an international, open-label, phase III, randomized trial involving 186 patients with refractory hepatitis C virus type 1b infection, Dr. Pietro Andreone and his colleagues reported in the August 2014 issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

Twelve weeks of treatment using the combination regimen plus ribavirin (91 patients) or the same regimen without ribavirin (95 patients) produced sustained virologic responses (SVRs) that were noninferior to historic SVRs reported in the literature for comparable patients treated with telaprevir plus pegylated-interferon plus ribavirin.

Source: American Gastroenterological Institute

None of the patients taking the new combination regimen experienced virologic failure while taking the drugs or relapse during the year after completing treatment. And adverse effects were characterized as "generally mild and manageable," said Dr. Andreone of the department of medical science and surgery, University of Bologna (Italy), and his associates.

HCV type 1b is the most prevalent genotype worldwide. Patients with this genotype who have failed on standard treatments "have not been extensively studied with currently approved or investigational interferon-free regimens, hence this large patient population represents a group with unmet need," the investigators noted.

They assessed such patients at 43 medical centers in Austria, Belgium, Italy, the Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Turkey, and the United States. All were aged between 18 and 70 years, and all were free of cirrhosis and coinfections.

The daily oral combination regimen consisted of ABT-450, a protease inhibitor that has shown in-vitro antiviral activity; ritonavir, a CYP3A4 inhibitor that enables once-daily rather than more frequent dosing of the ABT-450; ombitasvir, an HCV NS5A inhibitor; and dasabuvir, an HCV NS5B RNA nonnucleoside polymerase inhibitor.

The primary efficacy endpoint was an SVR rate noninferior to the historical rate for interferon-containing regimens in comparable patients. In the intention-to-treat analysis, the SVRs met and surpassed that standard, at 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.

Moreover, of the three patients who did not achieve a sustained virologic response, two had discontinued the study drug because of adverse events and one was lost to follow-up after only 4 weeks of treatment.

The most common adverse events were fatigue, headache, and nausea, all of which were significantly more frequent among patients taking ribavirin. Insomnia, anemia, rash, and elevated bilirubin also were related to ribavirin and were easily managed.

Only two patients discontinued treatment due to adverse events, neither of which were considered to be related to a study drug. One patient developed pancreatitis and another developed anxiety, tachycardia, and dyspnea.

Three other serious adverse events – cellulitis, nephrolithiasis, and osteoarthritis – also were judged to be unrelated to the study treatments.

Declines in hemoglobin levels occurred in 42% of the patients who received ribavirin but only 5.5% of those who did not. However, clinically significant declines occurred in only two patients, and neither of them required transfusions or erythropoietin.

Their findings show that 12 weeks of combined oral ABT-450/ritonavir/ombitasvir/dasabuvir therapy without ribavirin is at least as effective as interferon-containing regimens, and it produces significantly fewer and less severe adverse effects, the investigators said.

This study was somewhat limited in that it used an open-label design and did not include patients with concomitant cirrhosis, hepatitis B viral infection, or HIV infection, they added.

This study was sponsored by AbbVie, which also participated in the study design, data collection and analysis, and manuscript preparation. Dr. Andreone reported receiving research support from, being a consultant for, or serving on advisory committees for Roche, Merck, Gilead Sciences, Janssen Cilag, AbbVie, Boehringer Ingelheim, and BMS; his associates reported ties to numerous industry sources.

Among adults at average risk for colorectal cancer who undergo screening colonoscopy, the yield of large polyps and tumors varies widely by patient age, sex, race, and ethnicity. This means that an across-the-board recommendation to initiate screening for all patients at a particular age "may not appear rational and could negatively impact adherence," Dr. David A. Lieberman and his colleagues said in the August issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

In what they described as "the largest and most comprehensive analysis of average-risk screening with colonoscopy in the United States," the investigators found that the rate of detecting large (and therefore likely advanced) neoplastic lesions was much higher or lower at any given age, depending on the patient’s sex, race, and ethnicity. So the fact that most practice guidelines uniformly recommend initiating colonoscopy screens at age 50 years doesn’t make sense.

"We believe these data, combined with [those of] prior studies, are compelling enough to consider customization of the initiation age of screening based on the risk of large polyps," said Dr. Lieberman and his associates at Oregon Health & Science University, Portland.

They analyzed information from the Clinical Outcomes Research Initiative database, which includes endoscopy findings from 84 diverse practice settings across the country that are representative of all U.S. community, academic, and Veterans Administration endoscopy centers. They included 327,785 exams of patients aged 40 years and older who were at average risk for colorectal cancer and were screened in 2000 through 2011.

Women accounted for half of the study subjects, except for those examined at VA centers, who were predominately male. The study population was 83.6% white, 5.7% black, and 7.7% Hispanic. More than 95% of the participants were aged 50-79 years.

The outcome of interest was the detection of a polyp or tumor larger than 9 mm. "These large lesions are a surrogate for advanced neoplasia," the investigators said.

The prevalence of large neoplasias rose steadily with increasing age across all races and ethnicities and in both sexes.

Across all age groups, women had a lower prevalence of large polyps than men did, suggesting that the initiation of screening colonoscopy can be safely delayed until age 60 years, at least in white and Hispanic women.

Among men younger than 50 years, the prevalence of large polyps was similar between whites (5.3%) and blacks (5.0%). However, the sample of black men in this age group was small (380 patients), so it is possible that this study was simply underpowered to detect the well-known excess of colorectal neoplasias in younger black men.

The prevalence of large polyps was higher in black men than did white men at all other ages until the age of 70 years, at which point the rates even out. Prevalences were 7.1% vs. 6.2% at 50-54 years, 8.5% vs. 7.4% at 55-59 years, 11.5% vs. 8.6% at 60-64 years, and 12.0% vs. 9.7% at 65-69 years.

Black women had a higher prevalence of large polyps than did white women until age 65 years, when the rates evened out. Prevalences were 5.2% vs. 4.2% at 50-54 years, 6.6% vs. 4.5% at 55-59 years, and 6.9% vs. 5.2% at 60-64 years.

These findings "support intensification of screening in black men and women at age 50 years," Dr. Lieberman and his associates said.

Hispanic men and women had a 25% lower rate of polyps than did whites from age 50 through age 79. This finding suggests that initiation of screening colonoscopy can be delayed in Hispanic men and especially in Hispanic women.

The researchers used white men aged 50-54 years as a reference group to compare rates of detection across the study groups. Screening colonoscopy detected large polyps in 6.2% of white men aged 50-54 years. To achieve a similar yield in Hispanic men or black women, they wouldn’t need to be screened until age 55-59 years. To achieve it in Hispanic women, they wouldn’t need to be screened until age 70-74 years.

This study was supported by the National Institute of Digestive and Kidney Diseases. Dr. Lieberman and his associates reported no relevant financial conflicts of interest.

Among adults at average risk for colorectal cancer who undergo screening colonoscopy, the yield of large polyps and tumors varies widely by patient age, sex, race, and ethnicity. This means that an across-the-board recommendation to initiate screening for all patients at a particular age "may not appear rational and could negatively impact adherence," Dr. David A. Lieberman and his colleagues said in the August issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

In what they described as "the largest and most comprehensive analysis of average-risk screening with colonoscopy in the United States," the investigators found that the rate of detecting large (and therefore likely advanced) neoplastic lesions was much higher or lower at any given age, depending on the patient’s sex, race, and ethnicity. So the fact that most practice guidelines uniformly recommend initiating colonoscopy screens at age 50 years doesn’t make sense.

"We believe these data, combined with [those of] prior studies, are compelling enough to consider customization of the initiation age of screening based on the risk of large polyps," said Dr. Lieberman and his associates at Oregon Health & Science University, Portland.

They analyzed information from the Clinical Outcomes Research Initiative database, which includes endoscopy findings from 84 diverse practice settings across the country that are representative of all U.S. community, academic, and Veterans Administration endoscopy centers. They included 327,785 exams of patients aged 40 years and older who were at average risk for colorectal cancer and were screened in 2000 through 2011.

Women accounted for half of the study subjects, except for those examined at VA centers, who were predominately male. The study population was 83.6% white, 5.7% black, and 7.7% Hispanic. More than 95% of the participants were aged 50-79 years.

The outcome of interest was the detection of a polyp or tumor larger than 9 mm. "These large lesions are a surrogate for advanced neoplasia," the investigators said.

The prevalence of large neoplasias rose steadily with increasing age across all races and ethnicities and in both sexes.

Across all age groups, women had a lower prevalence of large polyps than men did, suggesting that the initiation of screening colonoscopy can be safely delayed until age 60 years, at least in white and Hispanic women.

Among men younger than 50 years, the prevalence of large polyps was similar between whites (5.3%) and blacks (5.0%). However, the sample of black men in this age group was small (380 patients), so it is possible that this study was simply underpowered to detect the well-known excess of colorectal neoplasias in younger black men.

The prevalence of large polyps was higher in black men than did white men at all other ages until the age of 70 years, at which point the rates even out. Prevalences were 7.1% vs. 6.2% at 50-54 years, 8.5% vs. 7.4% at 55-59 years, 11.5% vs. 8.6% at 60-64 years, and 12.0% vs. 9.7% at 65-69 years.

Black women had a higher prevalence of large polyps than did white women until age 65 years, when the rates evened out. Prevalences were 5.2% vs. 4.2% at 50-54 years, 6.6% vs. 4.5% at 55-59 years, and 6.9% vs. 5.2% at 60-64 years.

These findings "support intensification of screening in black men and women at age 50 years," Dr. Lieberman and his associates said.

Hispanic men and women had a 25% lower rate of polyps than did whites from age 50 through age 79. This finding suggests that initiation of screening colonoscopy can be delayed in Hispanic men and especially in Hispanic women.

The researchers used white men aged 50-54 years as a reference group to compare rates of detection across the study groups. Screening colonoscopy detected large polyps in 6.2% of white men aged 50-54 years. To achieve a similar yield in Hispanic men or black women, they wouldn’t need to be screened until age 55-59 years. To achieve it in Hispanic women, they wouldn’t need to be screened until age 70-74 years.

This study was supported by the National Institute of Digestive and Kidney Diseases. Dr. Lieberman and his associates reported no relevant financial conflicts of interest.

Among adults at average risk for colorectal cancer who undergo screening colonoscopy, the yield of large polyps and tumors varies widely by patient age, sex, race, and ethnicity. This means that an across-the-board recommendation to initiate screening for all patients at a particular age "may not appear rational and could negatively impact adherence," Dr. David A. Lieberman and his colleagues said in the August issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).

In what they described as "the largest and most comprehensive analysis of average-risk screening with colonoscopy in the United States," the investigators found that the rate of detecting large (and therefore likely advanced) neoplastic lesions was much higher or lower at any given age, depending on the patient’s sex, race, and ethnicity. So the fact that most practice guidelines uniformly recommend initiating colonoscopy screens at age 50 years doesn’t make sense.

"We believe these data, combined with [those of] prior studies, are compelling enough to consider customization of the initiation age of screening based on the risk of large polyps," said Dr. Lieberman and his associates at Oregon Health & Science University, Portland.

They analyzed information from the Clinical Outcomes Research Initiative database, which includes endoscopy findings from 84 diverse practice settings across the country that are representative of all U.S. community, academic, and Veterans Administration endoscopy centers. They included 327,785 exams of patients aged 40 years and older who were at average risk for colorectal cancer and were screened in 2000 through 2011.

Women accounted for half of the study subjects, except for those examined at VA centers, who were predominately male. The study population was 83.6% white, 5.7% black, and 7.7% Hispanic. More than 95% of the participants were aged 50-79 years.

The outcome of interest was the detection of a polyp or tumor larger than 9 mm. "These large lesions are a surrogate for advanced neoplasia," the investigators said.

The prevalence of large neoplasias rose steadily with increasing age across all races and ethnicities and in both sexes.

Across all age groups, women had a lower prevalence of large polyps than men did, suggesting that the initiation of screening colonoscopy can be safely delayed until age 60 years, at least in white and Hispanic women.

Among men younger than 50 years, the prevalence of large polyps was similar between whites (5.3%) and blacks (5.0%). However, the sample of black men in this age group was small (380 patients), so it is possible that this study was simply underpowered to detect the well-known excess of colorectal neoplasias in younger black men.

The prevalence of large polyps was higher in black men than did white men at all other ages until the age of 70 years, at which point the rates even out. Prevalences were 7.1% vs. 6.2% at 50-54 years, 8.5% vs. 7.4% at 55-59 years, 11.5% vs. 8.6% at 60-64 years, and 12.0% vs. 9.7% at 65-69 years.

Black women had a higher prevalence of large polyps than did white women until age 65 years, when the rates evened out. Prevalences were 5.2% vs. 4.2% at 50-54 years, 6.6% vs. 4.5% at 55-59 years, and 6.9% vs. 5.2% at 60-64 years.

These findings "support intensification of screening in black men and women at age 50 years," Dr. Lieberman and his associates said.

Hispanic men and women had a 25% lower rate of polyps than did whites from age 50 through age 79. This finding suggests that initiation of screening colonoscopy can be delayed in Hispanic men and especially in Hispanic women.

The researchers used white men aged 50-54 years as a reference group to compare rates of detection across the study groups. Screening colonoscopy detected large polyps in 6.2% of white men aged 50-54 years. To achieve a similar yield in Hispanic men or black women, they wouldn’t need to be screened until age 55-59 years. To achieve it in Hispanic women, they wouldn’t need to be screened until age 70-74 years.

This study was supported by the National Institute of Digestive and Kidney Diseases. Dr. Lieberman and his associates reported no relevant financial conflicts of interest.

Only a minority of patients with longstanding inflammatory bowel disease – 19% of those with Crohn’s disease and 11% of those with ulcerative colitis – report having moderate to severe disability, Dr. Eran Israeli and his colleagues reported in the August issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.12.009).

These rates compare favorably with those for patients with other chronic inflammatory diseases of long duration such as multiple sclerosis and ankylosing spondylitis, they noted.

Until now, most studies of IBD-related disability "have focused narrowly on work and employment," while data have been limited regarding home, social, and psychological domains. Dr. Israeli and his associates assessed IBD-related disability across all of these domains by analyzing information from the ongoing Manitoba IBD Cohort Study. This longitudinal cohort included patients aged 16 years and older who had had their disease for at least a decade when they enrolled in 2002.The MICS-enrolled patients from a population-based research registry who were representative of the general population of IBD patients in Canada, and tracked disease-related factors through semiannual questionnaires and annual in-person interviews.

For their study, Dr. Israeli and his colleagues assessed disability in 125 of these study patients with Crohn’s disease and 119 with ulcerative colitis 8 years after they had enrolled in the MCIS. Approximately 60% were women, and most of the participants were younger than 50 years, married, and working full- or part-time jobs. The median duration of IBD at the time of the disability assessment was 13 years, said Dr. Israeli of Hadassah-Hebrew University Medical Center, Jerusalem, and his associates.

Overall, 19% of the patients with Crohn’s disease and 11% of those with ulcerative colitis reported having significant disability across all spheres of life, as measured using the World Health Organization Disability Schedule and the Work and Social Adjustment Scale.

These rates were remarkably consistent across all domains studied, including patients’ perception of their stress level, as measured by the Cohen Perceived Stress Scale; current emotional distress, as measured by the Brief Symptom Inventory; and quality of life, as measured by the Inflammatory Bowel Disease Questionnaire.

Not only was the prevalence of disability higher in Crohn’s disease than in ulcerative colitis, but the severity of disability also was significantly greater in the realms of home management and social relationships. Patients with Crohn’s disease also reported greater emotional distress (depression and anxiety), higher stress levels, and poorer quality of life than those with ulcerative colitis.

Overall, 27% of the participants had a history of major depression, which often predated the development of IBD. This rate was much higher than that in the general population, and it was higher still in the subgroup of patients with the most significant disability: Depression was reported in 57% of the significantly disabled patients with Crohn’s disease and 37% among the significantly disabled patients with ulcerative colitis.

Both a history of depression and a higher degree of disease activity over time were significant predictors of disability. "The strong predictive effect of lifetime history of depression on disability in IBD suggests that when depression is identified, clinicians should be as aggressive in its treatment as they are in treating the luminal manifestations of the disease," the investigators said.

Somewhat surprisingly, a history of multiple IBD-related surgeries did not predict disability. This may be because surgical resection leads to long-term remission of symptoms, at least among patients with ulcerative colitis, they added.

[email protected]

Only a minority of patients with longstanding inflammatory bowel disease – 19% of those with Crohn’s disease and 11% of those with ulcerative colitis – report having moderate to severe disability, Dr. Eran Israeli and his colleagues reported in the August issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.12.009).

These rates compare favorably with those for patients with other chronic inflammatory diseases of long duration such as multiple sclerosis and ankylosing spondylitis, they noted.

Until now, most studies of IBD-related disability "have focused narrowly on work and employment," while data have been limited regarding home, social, and psychological domains. Dr. Israeli and his associates assessed IBD-related disability across all of these domains by analyzing information from the ongoing Manitoba IBD Cohort Study. This longitudinal cohort included patients aged 16 years and older who had had their disease for at least a decade when they enrolled in 2002.The MICS-enrolled patients from a population-based research registry who were representative of the general population of IBD patients in Canada, and tracked disease-related factors through semiannual questionnaires and annual in-person interviews.

For their study, Dr. Israeli and his colleagues assessed disability in 125 of these study patients with Crohn’s disease and 119 with ulcerative colitis 8 years after they had enrolled in the MCIS. Approximately 60% were women, and most of the participants were younger than 50 years, married, and working full- or part-time jobs. The median duration of IBD at the time of the disability assessment was 13 years, said Dr. Israeli of Hadassah-Hebrew University Medical Center, Jerusalem, and his associates.

Overall, 19% of the patients with Crohn’s disease and 11% of those with ulcerative colitis reported having significant disability across all spheres of life, as measured using the World Health Organization Disability Schedule and the Work and Social Adjustment Scale.

These rates were remarkably consistent across all domains studied, including patients’ perception of their stress level, as measured by the Cohen Perceived Stress Scale; current emotional distress, as measured by the Brief Symptom Inventory; and quality of life, as measured by the Inflammatory Bowel Disease Questionnaire.

Not only was the prevalence of disability higher in Crohn’s disease than in ulcerative colitis, but the severity of disability also was significantly greater in the realms of home management and social relationships. Patients with Crohn’s disease also reported greater emotional distress (depression and anxiety), higher stress levels, and poorer quality of life than those with ulcerative colitis.

Overall, 27% of the participants had a history of major depression, which often predated the development of IBD. This rate was much higher than that in the general population, and it was higher still in the subgroup of patients with the most significant disability: Depression was reported in 57% of the significantly disabled patients with Crohn’s disease and 37% among the significantly disabled patients with ulcerative colitis.

Both a history of depression and a higher degree of disease activity over time were significant predictors of disability. "The strong predictive effect of lifetime history of depression on disability in IBD suggests that when depression is identified, clinicians should be as aggressive in its treatment as they are in treating the luminal manifestations of the disease," the investigators said.

Somewhat surprisingly, a history of multiple IBD-related surgeries did not predict disability. This may be because surgical resection leads to long-term remission of symptoms, at least among patients with ulcerative colitis, they added.

[email protected]

Only a minority of patients with longstanding inflammatory bowel disease – 19% of those with Crohn’s disease and 11% of those with ulcerative colitis – report having moderate to severe disability, Dr. Eran Israeli and his colleagues reported in the August issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.12.009).

These rates compare favorably with those for patients with other chronic inflammatory diseases of long duration such as multiple sclerosis and ankylosing spondylitis, they noted.

Until now, most studies of IBD-related disability "have focused narrowly on work and employment," while data have been limited regarding home, social, and psychological domains. Dr. Israeli and his associates assessed IBD-related disability across all of these domains by analyzing information from the ongoing Manitoba IBD Cohort Study. This longitudinal cohort included patients aged 16 years and older who had had their disease for at least a decade when they enrolled in 2002.The MICS-enrolled patients from a population-based research registry who were representative of the general population of IBD patients in Canada, and tracked disease-related factors through semiannual questionnaires and annual in-person interviews.

For their study, Dr. Israeli and his colleagues assessed disability in 125 of these study patients with Crohn’s disease and 119 with ulcerative colitis 8 years after they had enrolled in the MCIS. Approximately 60% were women, and most of the participants were younger than 50 years, married, and working full- or part-time jobs. The median duration of IBD at the time of the disability assessment was 13 years, said Dr. Israeli of Hadassah-Hebrew University Medical Center, Jerusalem, and his associates.

Overall, 19% of the patients with Crohn’s disease and 11% of those with ulcerative colitis reported having significant disability across all spheres of life, as measured using the World Health Organization Disability Schedule and the Work and Social Adjustment Scale.

These rates were remarkably consistent across all domains studied, including patients’ perception of their stress level, as measured by the Cohen Perceived Stress Scale; current emotional distress, as measured by the Brief Symptom Inventory; and quality of life, as measured by the Inflammatory Bowel Disease Questionnaire.

Not only was the prevalence of disability higher in Crohn’s disease than in ulcerative colitis, but the severity of disability also was significantly greater in the realms of home management and social relationships. Patients with Crohn’s disease also reported greater emotional distress (depression and anxiety), higher stress levels, and poorer quality of life than those with ulcerative colitis.

Overall, 27% of the participants had a history of major depression, which often predated the development of IBD. This rate was much higher than that in the general population, and it was higher still in the subgroup of patients with the most significant disability: Depression was reported in 57% of the significantly disabled patients with Crohn’s disease and 37% among the significantly disabled patients with ulcerative colitis.

Both a history of depression and a higher degree of disease activity over time were significant predictors of disability. "The strong predictive effect of lifetime history of depression on disability in IBD suggests that when depression is identified, clinicians should be as aggressive in its treatment as they are in treating the luminal manifestations of the disease," the investigators said.

Somewhat surprisingly, a history of multiple IBD-related surgeries did not predict disability. This may be because surgical resection leads to long-term remission of symptoms, at least among patients with ulcerative colitis, they added.

[email protected]

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.

Once-daily ramosetron improved stool consistency in male patients with diarrhea-predominant irritable bowel syndrome, Dr. Shin Fukudo and colleagues reported in the June issue of Clinical Gastroenterology and Hepatology 2014 [doi:10.1016/j.cgh.2013.11.024].

Indeed, compared with other 5-hydroxytryptamine₃ (5-HT3) agonists in its class, the "high selectivity, clear efficacy, and lower incidence of serious adverse events suggest that ramosetron is the most promising therapeutic agent for IBS-D [irritable bowel syndrome–diarrhea subtype]," Dr. Fukudo and associates wrote.

In the current study, which was funded by the drug’s maker, Astellas Pharma, Dr. Fukudo of Tohoku University Graduate School of Medicine, in Sendai, Japan, looked at male patients aged 20-64 years diagnosed with IBS-D according to Rome III criteria.

To begin, subjects were monitored for 1 week to gather baseline assessments of severity of abdominal pain/discomfort, using a five-point ordinate scale, as well as stool consistency – the primary endpoint of the study – using the Bristol Stool Form Scale (BSFS).

For inclusion in the analysis, patients had to demonstrate mean abdominal pain/discomfort scores of at least 0.7 during the baseline period, have no type 1 or 2 stool form, and have an overall mean score of greater than 5 on the BSFS.

Patients were then randomized to a 12-week regimen of either ramosetron 5 mcg daily before breakfast or placebo and began recording their IBS symptoms daily on paper diary cards as well as in a voice-activated electronic database system.

Overall, 148 placebo patients and 147 ramosetron-treated patients were included in the analysis.

Looking at the primary endpoint, Dr. Fukudo found that in the first month, 50.3% of patients in the ramosetron group reported improvement in stool consistency (95% confidence interval, 42.0%-58.7%) versus 19.6% among placebo patients (95% CI, 13.5%-26.9%) (P less than 0.001).

That trend held for the remainder of the study, with a significantly greater portion of ramosetron patients consistently logging gains in stool consistency from month to month.

Similarly, the ramosetron group also recorded changes in the severity of abdominal pain/discomfort week from baseline, with a decrease in severity of 0.78, compared with mean weekly reductions of 0.60 among placebo patients.

The difference between groups, however, was only significant at week 5, with a mean 0.70 decrease in symptoms over the previous week, compared with 0.48 for placebo (P = .012).

Safety profiles, meanwhile, were similar for both drugs: adverse events occurred in 46.9% and 51.7% of ramosetron and placebo patients, respectively, with constipation occurring in 3.4% of treatment patients versus 0.7% of placebo patients, a nonsignificant difference.

Moreover, "All episodes of constipation and hard stools in the ramosetron group, assumed to be caused by the pharmacologic actions of ramosetron, were classified as mild and resolved early without using rescue drugs."

According to the researchers, the efficacy of ramosetron likely stems from the "crucial role" that 5-hydroxytryptamine plays in IBS-D pathophysiology.

"IBS-D patients have exaggerated colonic motility in response to colorectal distention," they wrote.

Since the distention-induced peristaltic reflex is mediated by 5-HT, and since abnormal neurotransmission of 5-HT via the 5-HT3 receptor has been reported in IBS-diarrhea patients, "Use of a 5-HT3 antagonist for IBS-D patients is a logical consequence."

In addition to the disclosure that the study was funded by Astellas Pharma, Dr. Fukudo also disclosed working as a contracted consultant to the company, along with a coinvestigator; the three remaining authors are Astellas employees.

Nonselective beta-blockers are contraindicated in cirrhosis with spontaneous bacterial peritonitis, wrote Dr. Mattias Mandorfer and his colleagues in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2014.03.005).

Indeed, in a retrospective analysis, the drugs increased the length of hospitalization and the rate of hepatorenal syndrome, while decreasing overall transplant-free survival.

"These observations suggest that nonselective beta-blocker treatment should be discontinued at the first development of spontaneous bacterial peritonitis (SBP), raising the question of whether to permanently discontinue or to restart ... treatment after resolving the SBP episode," they added.

Dr. Mandorfer, of the Medical University of Vienna, and his colleagues followed 607 consecutive cirrhosis patients who underwent their first paracentesis at that institution between 2006 and 2011.

Overall, 245 patients were taking beta-blockers, including propranolol, with doses ranging from 20 to 120 mg, and carvedilol, with doses between 6.25 and 25 mg.

Spontaneous bacterial peritonitis was defined as an ascitic polymorphonuclear neutrophil count greater than 250 cells/mL with no evident source of infection.

A total of 182 cases of a first SBP infection were detected during the study period and included for analysis (86 in beta-blocker patients), with incidence rates comparable between beta-blocker and non–beta-blocker cohorts (0.107 vs, 0.117 per person-year, respectively).

The authors found that a higher proportion of beta-blocker patients were hemodynamically unstable, with 38% registering mean systolic arterial pressures less than 100 mm Hg at the time of first paracentesis during an SBP episode, compared with 18% of non–beta-blocker patients (P = .002).

And although variceal bleeding rates were similar between cohorts, beta-blocker patients tallied overall longer durations of hospitalization than did their untreated counterparts (33.4 vs. 28.8 days per person-year).

Looking at the development of hepatorenal syndrome, Dr. Mandorfer also noted that the incidence was significantly higher in patients taking beta-blockers (24%) than in patients who were not (11%; P = .027).

Perhaps most importantly, while beta-blocker treatment was associated with improved transplant-free survival generally, after SBP diagnosis, taking beta-blockers resulted in a lower transplant-free survival (hazard ratio, 1.58; 95% confidence interval, 1.098-2.274; P = .014) after adjustment for the presence of varices and the Child-Pugh score.

According to Dr. Mandorfer, the present study adds another voice to the "lively debate" that began after a 2010 study showed that beta-blockers had deleterious effects on survival (Hepatology 2010;52:1017-22).

And while these findings support the "window hypothesis," which posits that the optimal "window" for beta-blocker treatment opens at the diagnosis of cirrhosis but closes at the development of SBP, "whether the therapeutic window for [beta-blocker] treatment reopens after resolving the SBP episode remains unclear," they wrote.

Indeed, "The development of bacterial infections might define a distinct group of critically ill patients with cirrhosis with a highly restricted prognosis in which maintaining the circulatory reserve is crucial not only during the acute phase of infection but also later on," they added.

"Prospective studies are highly encouraged to investigate the appropriate, stage-dependent use of this cornerstone in the treatment of portal hypertension."

The authors stated that they had no conflicts of interest and disclosed no funding for this study.

Nonselective beta-blockers are contraindicated in cirrhosis with spontaneous bacterial peritonitis, wrote Dr. Mattias Mandorfer and his colleagues in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2014.03.005).

Indeed, in a retrospective analysis, the drugs increased the length of hospitalization and the rate of hepatorenal syndrome, while decreasing overall transplant-free survival.

"These observations suggest that nonselective beta-blocker treatment should be discontinued at the first development of spontaneous bacterial peritonitis (SBP), raising the question of whether to permanently discontinue or to restart ... treatment after resolving the SBP episode," they added.

Dr. Mandorfer, of the Medical University of Vienna, and his colleagues followed 607 consecutive cirrhosis patients who underwent their first paracentesis at that institution between 2006 and 2011.

Overall, 245 patients were taking beta-blockers, including propranolol, with doses ranging from 20 to 120 mg, and carvedilol, with doses between 6.25 and 25 mg.

Spontaneous bacterial peritonitis was defined as an ascitic polymorphonuclear neutrophil count greater than 250 cells/mL with no evident source of infection.

A total of 182 cases of a first SBP infection were detected during the study period and included for analysis (86 in beta-blocker patients), with incidence rates comparable between beta-blocker and non–beta-blocker cohorts (0.107 vs, 0.117 per person-year, respectively).

The authors found that a higher proportion of beta-blocker patients were hemodynamically unstable, with 38% registering mean systolic arterial pressures less than 100 mm Hg at the time of first paracentesis during an SBP episode, compared with 18% of non–beta-blocker patients (P = .002).

And although variceal bleeding rates were similar between cohorts, beta-blocker patients tallied overall longer durations of hospitalization than did their untreated counterparts (33.4 vs. 28.8 days per person-year).

Looking at the development of hepatorenal syndrome, Dr. Mandorfer also noted that the incidence was significantly higher in patients taking beta-blockers (24%) than in patients who were not (11%; P = .027).

Perhaps most importantly, while beta-blocker treatment was associated with improved transplant-free survival generally, after SBP diagnosis, taking beta-blockers resulted in a lower transplant-free survival (hazard ratio, 1.58; 95% confidence interval, 1.098-2.274; P = .014) after adjustment for the presence of varices and the Child-Pugh score.

According to Dr. Mandorfer, the present study adds another voice to the "lively debate" that began after a 2010 study showed that beta-blockers had deleterious effects on survival (Hepatology 2010;52:1017-22).

And while these findings support the "window hypothesis," which posits that the optimal "window" for beta-blocker treatment opens at the diagnosis of cirrhosis but closes at the development of SBP, "whether the therapeutic window for [beta-blocker] treatment reopens after resolving the SBP episode remains unclear," they wrote.

Indeed, "The development of bacterial infections might define a distinct group of critically ill patients with cirrhosis with a highly restricted prognosis in which maintaining the circulatory reserve is crucial not only during the acute phase of infection but also later on," they added.

"Prospective studies are highly encouraged to investigate the appropriate, stage-dependent use of this cornerstone in the treatment of portal hypertension."

The authors stated that they had no conflicts of interest and disclosed no funding for this study.

Nonselective beta-blockers are contraindicated in cirrhosis with spontaneous bacterial peritonitis, wrote Dr. Mattias Mandorfer and his colleagues in the June issue of Gastroenterology (doi: 10.1053/j.gastro.2014.03.005).

Indeed, in a retrospective analysis, the drugs increased the length of hospitalization and the rate of hepatorenal syndrome, while decreasing overall transplant-free survival.

"These observations suggest that nonselective beta-blocker treatment should be discontinued at the first development of spontaneous bacterial peritonitis (SBP), raising the question of whether to permanently discontinue or to restart ... treatment after resolving the SBP episode," they added.

Dr. Mandorfer, of the Medical University of Vienna, and his colleagues followed 607 consecutive cirrhosis patients who underwent their first paracentesis at that institution between 2006 and 2011.

Overall, 245 patients were taking beta-blockers, including propranolol, with doses ranging from 20 to 120 mg, and carvedilol, with doses between 6.25 and 25 mg.

Spontaneous bacterial peritonitis was defined as an ascitic polymorphonuclear neutrophil count greater than 250 cells/mL with no evident source of infection.

A total of 182 cases of a first SBP infection were detected during the study period and included for analysis (86 in beta-blocker patients), with incidence rates comparable between beta-blocker and non–beta-blocker cohorts (0.107 vs, 0.117 per person-year, respectively).

The authors found that a higher proportion of beta-blocker patients were hemodynamically unstable, with 38% registering mean systolic arterial pressures less than 100 mm Hg at the time of first paracentesis during an SBP episode, compared with 18% of non–beta-blocker patients (P = .002).

And although variceal bleeding rates were similar between cohorts, beta-blocker patients tallied overall longer durations of hospitalization than did their untreated counterparts (33.4 vs. 28.8 days per person-year).

Looking at the development of hepatorenal syndrome, Dr. Mandorfer also noted that the incidence was significantly higher in patients taking beta-blockers (24%) than in patients who were not (11%; P = .027).

Perhaps most importantly, while beta-blocker treatment was associated with improved transplant-free survival generally, after SBP diagnosis, taking beta-blockers resulted in a lower transplant-free survival (hazard ratio, 1.58; 95% confidence interval, 1.098-2.274; P = .014) after adjustment for the presence of varices and the Child-Pugh score.

According to Dr. Mandorfer, the present study adds another voice to the "lively debate" that began after a 2010 study showed that beta-blockers had deleterious effects on survival (Hepatology 2010;52:1017-22).

And while these findings support the "window hypothesis," which posits that the optimal "window" for beta-blocker treatment opens at the diagnosis of cirrhosis but closes at the development of SBP, "whether the therapeutic window for [beta-blocker] treatment reopens after resolving the SBP episode remains unclear," they wrote.

Indeed, "The development of bacterial infections might define a distinct group of critically ill patients with cirrhosis with a highly restricted prognosis in which maintaining the circulatory reserve is crucial not only during the acute phase of infection but also later on," they added.

"Prospective studies are highly encouraged to investigate the appropriate, stage-dependent use of this cornerstone in the treatment of portal hypertension."

The authors stated that they had no conflicts of interest and disclosed no funding for this study.

Inflammatory bowel disease patients rely on phone communication as much as or more than doctor visits for management of their disease, and heavier reliance may be a sign of impending emergency department visits.

Indeed, monitoring telephone activity among this population not only serves as a "clinical barometer," but also offers a glimpse into the "the currently unrecognized and unreimbursed effort that is made by clinic support staff in handling telephone calls in the care of IBD," wrote Dr. Claudia Ramos-Rivers and her colleagues in the June issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.11.015]).

Dr. Ramos-Rivers of the University of Pittsburgh looked at all incoming and outgoing calls registered at a tertiary care IBD clinic over 2 years, 2009 and 2010.

© Arkady Chubykin/Fotolia.com

In total, the clinic served 2,475 patients in 2009 and 3,118 in 2010, and logged 21,979 and 32,667 calls in each year, respectively.

According to the authors, during the 2-year period there were no spikes in activity from month to month.

Overall, more than half (52%) of patient-generated calls were related to a problem or follow-up question, and 25% were nurse-generated calls with a resolution or plan.

The remaining calls were for refill requests (12%), insurance authorizations (10%), and form completion or records requests (1%).

The mean number of calls was 8.9/patient in 2009 and 10.5/patient in 2010.

Next, the researchers looked at clinical factors associated with higher telephone usage. They found that being female as well as having a diagnosis of Crohn’s disease conferred a greater likelihood of frequent phone contact, as did a history of previous IBD-related surgeries and clinic visits.

In fact, these so-called "high telephone encounter" patients had an average of five visits annually, vs. just one for less frequent callers (P less than .001).

Increased telephone encounters were also associated with CRP elevation (P less than 0.001), erythrocyte sedimentation rate (ESR) elevation (P less than .001), and prednisone prescriptions (P less than .001).

Finally, the researchers looked at the association between phone use and emergency department visits and/or hospitalizations.

As predicted, they found that in 2009, ED visits occurred among 6.4% of the "low" telephone contact group, compared with 36.4% of the high-volume calls group.

Hospitalizations followed a similar trend (3.9% of low-volume callers in 2009, vs. 39.7% of high-volume callers), as did 2010 data.

The authors conceded that their study is limited by the fact that all data were gathered from a single center.

Furthermore, "Correlating poor clinical outcome with telephone calls in patients who are instructed to contact our clinic if they are experiencing problems can be criticized as being tautologic," they added.

"We acknowledge this, but point out that the goal of our study was to identify a common ‘red flag’ that would function for all heterogenous subgroups of patients with IBD ... who were at risk of complications."

They concluded: "Increased telephone encounters recorded in the [electronic medical record] may function as an early warning mechanism to identify at-risk patients with IBD who may benefit from improved inflammatory and multidisciplinary treatment."

The authors disclosed no conflicts of interest. They stated that one researcher was supported by a grant from the Doris Duke Charitable Research Foundation, and two others by grants from the U.S. Army Medical Research and Materiel Command.

Inflammatory bowel disease patients rely on phone communication as much as or more than doctor visits for management of their disease, and heavier reliance may be a sign of impending emergency department visits.

Indeed, monitoring telephone activity among this population not only serves as a "clinical barometer," but also offers a glimpse into the "the currently unrecognized and unreimbursed effort that is made by clinic support staff in handling telephone calls in the care of IBD," wrote Dr. Claudia Ramos-Rivers and her colleagues in the June issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.11.015]).

Dr. Ramos-Rivers of the University of Pittsburgh looked at all incoming and outgoing calls registered at a tertiary care IBD clinic over 2 years, 2009 and 2010.

© Arkady Chubykin/Fotolia.com

In total, the clinic served 2,475 patients in 2009 and 3,118 in 2010, and logged 21,979 and 32,667 calls in each year, respectively.

According to the authors, during the 2-year period there were no spikes in activity from month to month.

Overall, more than half (52%) of patient-generated calls were related to a problem or follow-up question, and 25% were nurse-generated calls with a resolution or plan.

The remaining calls were for refill requests (12%), insurance authorizations (10%), and form completion or records requests (1%).

The mean number of calls was 8.9/patient in 2009 and 10.5/patient in 2010.

Next, the researchers looked at clinical factors associated with higher telephone usage. They found that being female as well as having a diagnosis of Crohn’s disease conferred a greater likelihood of frequent phone contact, as did a history of previous IBD-related surgeries and clinic visits.

In fact, these so-called "high telephone encounter" patients had an average of five visits annually, vs. just one for less frequent callers (P less than .001).

Increased telephone encounters were also associated with CRP elevation (P less than 0.001), erythrocyte sedimentation rate (ESR) elevation (P less than .001), and prednisone prescriptions (P less than .001).

Finally, the researchers looked at the association between phone use and emergency department visits and/or hospitalizations.

As predicted, they found that in 2009, ED visits occurred among 6.4% of the "low" telephone contact group, compared with 36.4% of the high-volume calls group.

Hospitalizations followed a similar trend (3.9% of low-volume callers in 2009, vs. 39.7% of high-volume callers), as did 2010 data.

The authors conceded that their study is limited by the fact that all data were gathered from a single center.

Furthermore, "Correlating poor clinical outcome with telephone calls in patients who are instructed to contact our clinic if they are experiencing problems can be criticized as being tautologic," they added.

"We acknowledge this, but point out that the goal of our study was to identify a common ‘red flag’ that would function for all heterogenous subgroups of patients with IBD ... who were at risk of complications."

They concluded: "Increased telephone encounters recorded in the [electronic medical record] may function as an early warning mechanism to identify at-risk patients with IBD who may benefit from improved inflammatory and multidisciplinary treatment."

The authors disclosed no conflicts of interest. They stated that one researcher was supported by a grant from the Doris Duke Charitable Research Foundation, and two others by grants from the U.S. Army Medical Research and Materiel Command.

Inflammatory bowel disease patients rely on phone communication as much as or more than doctor visits for management of their disease, and heavier reliance may be a sign of impending emergency department visits.

Indeed, monitoring telephone activity among this population not only serves as a "clinical barometer," but also offers a glimpse into the "the currently unrecognized and unreimbursed effort that is made by clinic support staff in handling telephone calls in the care of IBD," wrote Dr. Claudia Ramos-Rivers and her colleagues in the June issue of Clinical Gastroenterology and Hepatology (2014 [doi:10.1016/j.cgh.2013.11.015]).

Dr. Ramos-Rivers of the University of Pittsburgh looked at all incoming and outgoing calls registered at a tertiary care IBD clinic over 2 years, 2009 and 2010.

© Arkady Chubykin/Fotolia.com

In total, the clinic served 2,475 patients in 2009 and 3,118 in 2010, and logged 21,979 and 32,667 calls in each year, respectively.

According to the authors, during the 2-year period there were no spikes in activity from month to month.

Overall, more than half (52%) of patient-generated calls were related to a problem or follow-up question, and 25% were nurse-generated calls with a resolution or plan.

The remaining calls were for refill requests (12%), insurance authorizations (10%), and form completion or records requests (1%).

The mean number of calls was 8.9/patient in 2009 and 10.5/patient in 2010.

Next, the researchers looked at clinical factors associated with higher telephone usage. They found that being female as well as having a diagnosis of Crohn’s disease conferred a greater likelihood of frequent phone contact, as did a history of previous IBD-related surgeries and clinic visits.

In fact, these so-called "high telephone encounter" patients had an average of five visits annually, vs. just one for less frequent callers (P less than .001).

Increased telephone encounters were also associated with CRP elevation (P less than 0.001), erythrocyte sedimentation rate (ESR) elevation (P less than .001), and prednisone prescriptions (P less than .001).

Finally, the researchers looked at the association between phone use and emergency department visits and/or hospitalizations.

As predicted, they found that in 2009, ED visits occurred among 6.4% of the "low" telephone contact group, compared with 36.4% of the high-volume calls group.

Hospitalizations followed a similar trend (3.9% of low-volume callers in 2009, vs. 39.7% of high-volume callers), as did 2010 data.

The authors conceded that their study is limited by the fact that all data were gathered from a single center.

Furthermore, "Correlating poor clinical outcome with telephone calls in patients who are instructed to contact our clinic if they are experiencing problems can be criticized as being tautologic," they added.

"We acknowledge this, but point out that the goal of our study was to identify a common ‘red flag’ that would function for all heterogenous subgroups of patients with IBD ... who were at risk of complications."

They concluded: "Increased telephone encounters recorded in the [electronic medical record] may function as an early warning mechanism to identify at-risk patients with IBD who may benefit from improved inflammatory and multidisciplinary treatment."

The authors disclosed no conflicts of interest. They stated that one researcher was supported by a grant from the Doris Duke Charitable Research Foundation, and two others by grants from the U.S. Army Medical Research and Materiel Command.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.