From the AGA Journals

"Deep remission" of Crohn’s disease is associated with better quality of life, physical function, and cost savings.

Moreover, this composite clinical and endoscopic endpoint may be best accomplished through monitoring of the tumor necrosis factor antagonists’ plasma concentration, meaning that the pharmacokinetics of these therapies must be accounted for when optimizing drug treatment.

Those are the findings from two new analyses in the March issue of Clinical Gastroenterology and Hepatology, both by Dr. Jean-Frédéric Colombel of the Mount Sinai Hospital School of Medicine in New York.

In the first study, Dr. Colombel and his colleagues looked at 135 adults with moderate to severe ileocolonic Crohn’s enrolled in the EXTEND trial, a 52-week, randomized, double-blind placebo-controlled trial of adalimumab (doi:10.1016/j.cgh.2013.06.019).

The goal of EXTEND was to assess the effect of induction plus maintenance dosing of adalimumab, versus induction only. All patients received open-label adalimumab (160 mg and 80 mg at weeks 0 and 2, respectively) during the 4-week induction phase and were randomized at week 4 to receive adalimumab 40 mg every other week or placebo.

Overall, 19% of patients who received both adalimumab induction and maintenance therapy achieved so-called deep remission, defined as the absence of mucosal ulceration plus clinical remission (Crohn’s Disease Activity Index [CDAI], less than 150). Of the remaining responders, 8 had an absence of mucosal ulceration without clinical remission, and 19 had clinical remission with persistent mucosal ulceration.

Dr. Colombel and his coinvestigators found that patients in deep remission registered significantly fewer days absent from work, less work productivity impairment, greater work productivity, and less daily nonwork activity impairment, compared with patients who did not achieve deep remission (P less than .05 for all).

Moreover, at 1 year after therapy induction, significantly more patients in the deep remission group achieved remission according to the Inflammatory Bowel Disease Questionnaire (64% vs. 26%; P less than .05) and normal Short Form–36 Health Survey status (55% vs. 19%; P less than .05), compared with patients who were not in deep remission.

Finally, during the 40 weeks after early deep remission achievement, estimated savings among deep remission patients were $6,117 for direct medical costs and $4,243 for indirect costs related to productivity, compared with the costs for patients not in deep remission.

"This treatment target in CD [of deep remission], which combines symptom control with an objective indicator of inflammatory disease activity, still is evolving," wrote the investigators.

However, "current analysis provides preliminary evidence that early [deep remission] is achievable and may be a useful treatment target," they added.

The second analysis, also by Dr. Colombel, looked at the optimization of TNF antagonists in Crohn’s disease – specifically, at certolizumab pegol (doi:10.1016/j.cgh.2013.10.025).

In this post hoc analysis, Dr. Colombel looked at patients enrolled in the MUSIC trial, a 54-week, multicenter, single-arm open-label study assessing endoscopic improvement in patients with moderate to severe Crohn’s disease.

All patients received loading doses of certolizumab pegol 400 mg at 0, 2, and 4 weeks, followed by a maintenance dose of 400 mg every 4 weeks.

The authors found that at week 10, patients who achieved a clinical and an endoscopic response had "nominally higher" trough plasma certolizumab pegol concentrations at week 8 than those with no response or remission (16.5 mcg/mL for patients with a clinical response and 19.8 mcg/mL for patients with an endoscopic response, vs. 13.7 mcg/mL and 11.5 mcg/mL in the clinical and endoscopic nonresponders).

Similarly, patients who achieved clinical and endoscopic remission at week 10 also had nominally higher trough plasma concentrations at week 8, with clinical remission patients registering 17.6 mcg/mL (vs. 11.1 mcg/mL in patients without clinical remission) and endoscopic remission patients measuring 19.2 mcg/mL (vs. 12.6 mcg/mL in patients who did not achieve that endpoint).

"Plasma certolizumab pegol concentration is not readily measured in standard clinical practice at this time," wrote the authors.

However, "additional studies are needed to understand the relationships among clinical response, body weight, and plasma concentration of the TNF antagonist," they added.

Dr. Colombel and his colleagues disclosed numerous financial relationships with pharmaceutical companies, including the makers of adalimumab and certolizumab pegol; the EXTEND trial was funded by AbbieVie, the maker of adalimumab, and the MUSIC trial was funded by UCB Pharma, maker of certolizumab pegol.

"Deep remission" of Crohn’s disease is associated with better quality of life, physical function, and cost savings.

Moreover, this composite clinical and endoscopic endpoint may be best accomplished through monitoring of the tumor necrosis factor antagonists’ plasma concentration, meaning that the pharmacokinetics of these therapies must be accounted for when optimizing drug treatment.

Those are the findings from two new analyses in the March issue of Clinical Gastroenterology and Hepatology, both by Dr. Jean-Frédéric Colombel of the Mount Sinai Hospital School of Medicine in New York.

In the first study, Dr. Colombel and his colleagues looked at 135 adults with moderate to severe ileocolonic Crohn’s enrolled in the EXTEND trial, a 52-week, randomized, double-blind placebo-controlled trial of adalimumab (doi:10.1016/j.cgh.2013.06.019).

The goal of EXTEND was to assess the effect of induction plus maintenance dosing of adalimumab, versus induction only. All patients received open-label adalimumab (160 mg and 80 mg at weeks 0 and 2, respectively) during the 4-week induction phase and were randomized at week 4 to receive adalimumab 40 mg every other week or placebo.

Overall, 19% of patients who received both adalimumab induction and maintenance therapy achieved so-called deep remission, defined as the absence of mucosal ulceration plus clinical remission (Crohn’s Disease Activity Index [CDAI], less than 150). Of the remaining responders, 8 had an absence of mucosal ulceration without clinical remission, and 19 had clinical remission with persistent mucosal ulceration.

Dr. Colombel and his coinvestigators found that patients in deep remission registered significantly fewer days absent from work, less work productivity impairment, greater work productivity, and less daily nonwork activity impairment, compared with patients who did not achieve deep remission (P less than .05 for all).

Moreover, at 1 year after therapy induction, significantly more patients in the deep remission group achieved remission according to the Inflammatory Bowel Disease Questionnaire (64% vs. 26%; P less than .05) and normal Short Form–36 Health Survey status (55% vs. 19%; P less than .05), compared with patients who were not in deep remission.

Finally, during the 40 weeks after early deep remission achievement, estimated savings among deep remission patients were $6,117 for direct medical costs and $4,243 for indirect costs related to productivity, compared with the costs for patients not in deep remission.

"This treatment target in CD [of deep remission], which combines symptom control with an objective indicator of inflammatory disease activity, still is evolving," wrote the investigators.

However, "current analysis provides preliminary evidence that early [deep remission] is achievable and may be a useful treatment target," they added.

The second analysis, also by Dr. Colombel, looked at the optimization of TNF antagonists in Crohn’s disease – specifically, at certolizumab pegol (doi:10.1016/j.cgh.2013.10.025).

In this post hoc analysis, Dr. Colombel looked at patients enrolled in the MUSIC trial, a 54-week, multicenter, single-arm open-label study assessing endoscopic improvement in patients with moderate to severe Crohn’s disease.

All patients received loading doses of certolizumab pegol 400 mg at 0, 2, and 4 weeks, followed by a maintenance dose of 400 mg every 4 weeks.

The authors found that at week 10, patients who achieved a clinical and an endoscopic response had "nominally higher" trough plasma certolizumab pegol concentrations at week 8 than those with no response or remission (16.5 mcg/mL for patients with a clinical response and 19.8 mcg/mL for patients with an endoscopic response, vs. 13.7 mcg/mL and 11.5 mcg/mL in the clinical and endoscopic nonresponders).

Similarly, patients who achieved clinical and endoscopic remission at week 10 also had nominally higher trough plasma concentrations at week 8, with clinical remission patients registering 17.6 mcg/mL (vs. 11.1 mcg/mL in patients without clinical remission) and endoscopic remission patients measuring 19.2 mcg/mL (vs. 12.6 mcg/mL in patients who did not achieve that endpoint).

"Plasma certolizumab pegol concentration is not readily measured in standard clinical practice at this time," wrote the authors.

However, "additional studies are needed to understand the relationships among clinical response, body weight, and plasma concentration of the TNF antagonist," they added.

Dr. Colombel and his colleagues disclosed numerous financial relationships with pharmaceutical companies, including the makers of adalimumab and certolizumab pegol; the EXTEND trial was funded by AbbieVie, the maker of adalimumab, and the MUSIC trial was funded by UCB Pharma, maker of certolizumab pegol.

"Deep remission" of Crohn’s disease is associated with better quality of life, physical function, and cost savings.

Moreover, this composite clinical and endoscopic endpoint may be best accomplished through monitoring of the tumor necrosis factor antagonists’ plasma concentration, meaning that the pharmacokinetics of these therapies must be accounted for when optimizing drug treatment.

Those are the findings from two new analyses in the March issue of Clinical Gastroenterology and Hepatology, both by Dr. Jean-Frédéric Colombel of the Mount Sinai Hospital School of Medicine in New York.

In the first study, Dr. Colombel and his colleagues looked at 135 adults with moderate to severe ileocolonic Crohn’s enrolled in the EXTEND trial, a 52-week, randomized, double-blind placebo-controlled trial of adalimumab (doi:10.1016/j.cgh.2013.06.019).

The goal of EXTEND was to assess the effect of induction plus maintenance dosing of adalimumab, versus induction only. All patients received open-label adalimumab (160 mg and 80 mg at weeks 0 and 2, respectively) during the 4-week induction phase and were randomized at week 4 to receive adalimumab 40 mg every other week or placebo.

Overall, 19% of patients who received both adalimumab induction and maintenance therapy achieved so-called deep remission, defined as the absence of mucosal ulceration plus clinical remission (Crohn’s Disease Activity Index [CDAI], less than 150). Of the remaining responders, 8 had an absence of mucosal ulceration without clinical remission, and 19 had clinical remission with persistent mucosal ulceration.

Dr. Colombel and his coinvestigators found that patients in deep remission registered significantly fewer days absent from work, less work productivity impairment, greater work productivity, and less daily nonwork activity impairment, compared with patients who did not achieve deep remission (P less than .05 for all).

Moreover, at 1 year after therapy induction, significantly more patients in the deep remission group achieved remission according to the Inflammatory Bowel Disease Questionnaire (64% vs. 26%; P less than .05) and normal Short Form–36 Health Survey status (55% vs. 19%; P less than .05), compared with patients who were not in deep remission.

Finally, during the 40 weeks after early deep remission achievement, estimated savings among deep remission patients were $6,117 for direct medical costs and $4,243 for indirect costs related to productivity, compared with the costs for patients not in deep remission.

"This treatment target in CD [of deep remission], which combines symptom control with an objective indicator of inflammatory disease activity, still is evolving," wrote the investigators.

However, "current analysis provides preliminary evidence that early [deep remission] is achievable and may be a useful treatment target," they added.

The second analysis, also by Dr. Colombel, looked at the optimization of TNF antagonists in Crohn’s disease – specifically, at certolizumab pegol (doi:10.1016/j.cgh.2013.10.025).

In this post hoc analysis, Dr. Colombel looked at patients enrolled in the MUSIC trial, a 54-week, multicenter, single-arm open-label study assessing endoscopic improvement in patients with moderate to severe Crohn’s disease.

All patients received loading doses of certolizumab pegol 400 mg at 0, 2, and 4 weeks, followed by a maintenance dose of 400 mg every 4 weeks.

The authors found that at week 10, patients who achieved a clinical and an endoscopic response had "nominally higher" trough plasma certolizumab pegol concentrations at week 8 than those with no response or remission (16.5 mcg/mL for patients with a clinical response and 19.8 mcg/mL for patients with an endoscopic response, vs. 13.7 mcg/mL and 11.5 mcg/mL in the clinical and endoscopic nonresponders).

Similarly, patients who achieved clinical and endoscopic remission at week 10 also had nominally higher trough plasma concentrations at week 8, with clinical remission patients registering 17.6 mcg/mL (vs. 11.1 mcg/mL in patients without clinical remission) and endoscopic remission patients measuring 19.2 mcg/mL (vs. 12.6 mcg/mL in patients who did not achieve that endpoint).

"Plasma certolizumab pegol concentration is not readily measured in standard clinical practice at this time," wrote the authors.

However, "additional studies are needed to understand the relationships among clinical response, body weight, and plasma concentration of the TNF antagonist," they added.

Dr. Colombel and his colleagues disclosed numerous financial relationships with pharmaceutical companies, including the makers of adalimumab and certolizumab pegol; the EXTEND trial was funded by AbbieVie, the maker of adalimumab, and the MUSIC trial was funded by UCB Pharma, maker of certolizumab pegol.

Children with Crohn’s disease who received antitumor necrosis factor-alpha within 3 months of diagnosis experienced better overall clinical and growth outcomes at 1 year, compared with their counterparts who received an immunomodulator or those who received no immunomodulator therapy, results from an observational study demonstrated.

Although the current standard of practice for children recently diagnosed with Crohn’s disease (CD) involves early administration of immunomodulators after initial treatment with corticosteroids, some pediatric gastroenterologists, inspired by data from adult trials, "are adopting earlier introduction of anti-TNF-alpha therapy (without a trial of immunomodulators alone) in patients with inflammatory luminal CD judged to be at risk of serious chronically active disease," researchers led by Dr. Thomas D. Walters wrote in the February issue of Gastroenterology.

Source: American Gastroenterological Association

Dr. Walters of the Hospital for Sick Children in Toronto and his associates went on to note that while the efficacy of anti-TNF-alpha therapy is well established, "it has yet to be shown that the early use of this therapy in a specific group of pediatric patients (those with inflammatory luminal disease) is any more effective at improving patient outcomes than the classic step-up approach." In an effort to answer this question, the researchers analyzed data from the ongoing Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children With Crohn’s Disease (RS) trial, which was launched in 2008 at 28 pediatric gastroenterology centers in North America. The purpose of the current study was to determine whether anti-TNF-alpha monotherapy started within 3 months of diagnosis improves 1-year outcomes, compared with clinically similar patients who were treated with immunomodulator monotherapy started within 3 months of diagnosis or those who were treated with no immunotherapy during that time frame.

The researchers evaluated data from 552 patients who participated in the trial RISK between 2008 and 2012. They used propensity score matching "to avoid the usual problem of confounding by indication when using observational cohort data to explore differences in treatment response." More than half of the patients (61%) were male, their mean age was 11.8 years, and 63% had a Pediatric Crohn’s Disease Activity Index (PCDAI) score of greater than 30. The primary outcome of interest was corticosteroid-free clinical remission (defined as a PCDAI of 10 or less) at 1 year after diagnosis without luminal resection (Gastroenterology 2013 [doi: 10.1053/j.gastro.2013.10.027]).

Of the 552 patients, 68 received early anti-TNF-alpha monotherapy, 248 received early immunomodulator therapy, and 236 received no early immunotherapy. After propensity score matching, 85% of patients treated with early anti-TNF-alpha monotherapy achieved remission at 1 year, compared with 60% of those who were treated with early immunomodulator monotherapy and 54% of those who received no early immunotherapy, a difference that reached statistical significance (P =.0003). When the researchers factored in therapy after 3 months as a covariate, the results did not change; treatment with anti-TNF-alpha monotherapy remained significantly superior to early immunomodulator monotherapy (risk ratio, 1.51; P =.0004), while early immunomodulator monotherapy was no different from no early immunotherapy (RR, 1.00; P =.99).

Dr. Walters and his associates also observed that while weight and body mass index scores improved in all three groups, the height z score only showed improvement in the early anti-TNF-alpha group.

"Although our data clearly have added to the evidence base guiding treatment decisions after a diagnosis of Crohn’s disease in children, they should not be taken as an endorsement of one early therapeutic regimen over another," the authors concluded. "We were not able to identify any common clinical or laboratory characteristic that predicted response or failure with a particular approach. Further genetic, serologic, and microbiome analysis of our study cohort in conjunction with comparative efficacy results will better elucidate the value of different treatment decisions."

The study was supported by the Crohn’s and Colitis Foundation of America. Dr. Walters and many of his coauthors disclosed having received research support, consulting fees, or being on the speakers bureau for numerous pharmaceutical companies.

[email protected]

Children with Crohn’s disease who received antitumor necrosis factor-alpha within 3 months of diagnosis experienced better overall clinical and growth outcomes at 1 year, compared with their counterparts who received an immunomodulator or those who received no immunomodulator therapy, results from an observational study demonstrated.

Although the current standard of practice for children recently diagnosed with Crohn’s disease (CD) involves early administration of immunomodulators after initial treatment with corticosteroids, some pediatric gastroenterologists, inspired by data from adult trials, "are adopting earlier introduction of anti-TNF-alpha therapy (without a trial of immunomodulators alone) in patients with inflammatory luminal CD judged to be at risk of serious chronically active disease," researchers led by Dr. Thomas D. Walters wrote in the February issue of Gastroenterology.

Source: American Gastroenterological Association

Dr. Walters of the Hospital for Sick Children in Toronto and his associates went on to note that while the efficacy of anti-TNF-alpha therapy is well established, "it has yet to be shown that the early use of this therapy in a specific group of pediatric patients (those with inflammatory luminal disease) is any more effective at improving patient outcomes than the classic step-up approach." In an effort to answer this question, the researchers analyzed data from the ongoing Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children With Crohn’s Disease (RS) trial, which was launched in 2008 at 28 pediatric gastroenterology centers in North America. The purpose of the current study was to determine whether anti-TNF-alpha monotherapy started within 3 months of diagnosis improves 1-year outcomes, compared with clinically similar patients who were treated with immunomodulator monotherapy started within 3 months of diagnosis or those who were treated with no immunotherapy during that time frame.

The researchers evaluated data from 552 patients who participated in the trial RISK between 2008 and 2012. They used propensity score matching "to avoid the usual problem of confounding by indication when using observational cohort data to explore differences in treatment response." More than half of the patients (61%) were male, their mean age was 11.8 years, and 63% had a Pediatric Crohn’s Disease Activity Index (PCDAI) score of greater than 30. The primary outcome of interest was corticosteroid-free clinical remission (defined as a PCDAI of 10 or less) at 1 year after diagnosis without luminal resection (Gastroenterology 2013 [doi: 10.1053/j.gastro.2013.10.027]).

Of the 552 patients, 68 received early anti-TNF-alpha monotherapy, 248 received early immunomodulator therapy, and 236 received no early immunotherapy. After propensity score matching, 85% of patients treated with early anti-TNF-alpha monotherapy achieved remission at 1 year, compared with 60% of those who were treated with early immunomodulator monotherapy and 54% of those who received no early immunotherapy, a difference that reached statistical significance (P =.0003). When the researchers factored in therapy after 3 months as a covariate, the results did not change; treatment with anti-TNF-alpha monotherapy remained significantly superior to early immunomodulator monotherapy (risk ratio, 1.51; P =.0004), while early immunomodulator monotherapy was no different from no early immunotherapy (RR, 1.00; P =.99).

Dr. Walters and his associates also observed that while weight and body mass index scores improved in all three groups, the height z score only showed improvement in the early anti-TNF-alpha group.

"Although our data clearly have added to the evidence base guiding treatment decisions after a diagnosis of Crohn’s disease in children, they should not be taken as an endorsement of one early therapeutic regimen over another," the authors concluded. "We were not able to identify any common clinical or laboratory characteristic that predicted response or failure with a particular approach. Further genetic, serologic, and microbiome analysis of our study cohort in conjunction with comparative efficacy results will better elucidate the value of different treatment decisions."

The study was supported by the Crohn’s and Colitis Foundation of America. Dr. Walters and many of his coauthors disclosed having received research support, consulting fees, or being on the speakers bureau for numerous pharmaceutical companies.

[email protected]

Children with Crohn’s disease who received antitumor necrosis factor-alpha within 3 months of diagnosis experienced better overall clinical and growth outcomes at 1 year, compared with their counterparts who received an immunomodulator or those who received no immunomodulator therapy, results from an observational study demonstrated.

Although the current standard of practice for children recently diagnosed with Crohn’s disease (CD) involves early administration of immunomodulators after initial treatment with corticosteroids, some pediatric gastroenterologists, inspired by data from adult trials, "are adopting earlier introduction of anti-TNF-alpha therapy (without a trial of immunomodulators alone) in patients with inflammatory luminal CD judged to be at risk of serious chronically active disease," researchers led by Dr. Thomas D. Walters wrote in the February issue of Gastroenterology.

Source: American Gastroenterological Association

Dr. Walters of the Hospital for Sick Children in Toronto and his associates went on to note that while the efficacy of anti-TNF-alpha therapy is well established, "it has yet to be shown that the early use of this therapy in a specific group of pediatric patients (those with inflammatory luminal disease) is any more effective at improving patient outcomes than the classic step-up approach." In an effort to answer this question, the researchers analyzed data from the ongoing Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children With Crohn’s Disease (RS) trial, which was launched in 2008 at 28 pediatric gastroenterology centers in North America. The purpose of the current study was to determine whether anti-TNF-alpha monotherapy started within 3 months of diagnosis improves 1-year outcomes, compared with clinically similar patients who were treated with immunomodulator monotherapy started within 3 months of diagnosis or those who were treated with no immunotherapy during that time frame.

The researchers evaluated data from 552 patients who participated in the trial RISK between 2008 and 2012. They used propensity score matching "to avoid the usual problem of confounding by indication when using observational cohort data to explore differences in treatment response." More than half of the patients (61%) were male, their mean age was 11.8 years, and 63% had a Pediatric Crohn’s Disease Activity Index (PCDAI) score of greater than 30. The primary outcome of interest was corticosteroid-free clinical remission (defined as a PCDAI of 10 or less) at 1 year after diagnosis without luminal resection (Gastroenterology 2013 [doi: 10.1053/j.gastro.2013.10.027]).

Of the 552 patients, 68 received early anti-TNF-alpha monotherapy, 248 received early immunomodulator therapy, and 236 received no early immunotherapy. After propensity score matching, 85% of patients treated with early anti-TNF-alpha monotherapy achieved remission at 1 year, compared with 60% of those who were treated with early immunomodulator monotherapy and 54% of those who received no early immunotherapy, a difference that reached statistical significance (P =.0003). When the researchers factored in therapy after 3 months as a covariate, the results did not change; treatment with anti-TNF-alpha monotherapy remained significantly superior to early immunomodulator monotherapy (risk ratio, 1.51; P =.0004), while early immunomodulator monotherapy was no different from no early immunotherapy (RR, 1.00; P =.99).

Dr. Walters and his associates also observed that while weight and body mass index scores improved in all three groups, the height z score only showed improvement in the early anti-TNF-alpha group.

"Although our data clearly have added to the evidence base guiding treatment decisions after a diagnosis of Crohn’s disease in children, they should not be taken as an endorsement of one early therapeutic regimen over another," the authors concluded. "We were not able to identify any common clinical or laboratory characteristic that predicted response or failure with a particular approach. Further genetic, serologic, and microbiome analysis of our study cohort in conjunction with comparative efficacy results will better elucidate the value of different treatment decisions."

The study was supported by the Crohn’s and Colitis Foundation of America. Dr. Walters and many of his coauthors disclosed having received research support, consulting fees, or being on the speakers bureau for numerous pharmaceutical companies.

[email protected]

Immunosuppressive therapies for inflammatory bowel disease do not appear to be implicated in the increased risk for melanomas and hematologic malignancies seen in these patients, based on the results of a large database analysis and a separate meta-analysis published in the February edition of Clinical Gastroenterology and Hepatology.

The first study, based on a nationwide population-based cohort analysis conducted in Denmark, found that patients with inflammatory bowel disease (IBD) are at increased risk for cancer, in particular hematologic malignancies and melanoma at standardized incidence ratios of 1.9 and 1.4, respectively.

The second study, based on a systematic review and meta-analysis of the medical literature, found a diagnosis of Crohn’s disease or ulcerative colitis was associated with a 37% increase in the risk of developing melanoma. Melanoma risk was higher in studies performed before the introduction of biologic therapies in 1998, but not in those studies performed after 1998.

For the first study, researchers led by Dr. Michael D. Kappelman of the division of pediatric gastroenterology at the University of North Carolina at Chapel Hill used health care databases to identify patients in Denmark with a diagnosis of Crohn’s disease or ulcerative colitis from 1978 through 2010 (doi: 10.1016/j.cgh.2013.03.034). They followed the patients until the first occurrence of cancer, death, or emigration and used standardized incidence ratios (SIRs) to compare cancer incidence in patients with IBD with that expected in the general population.

"If immunosuppressive medications reduce the risk of gastrointestinal malignancy by suppressing intestinal inflammation but increase the risk of extraintestinal malignancies, IBD patients may be trading off one set of risks for another," the researchers wrote. "We therefore sought to evaluate both intestinal and extraintestinal malignancies comprehensively, as well as the occurrence of any invasive cancer, in a nationwide cohort of patients with IBD in Denmark."

The analysis included 13,756 patients with Crohn’s disease and 35,152 patients with ulcerative colitis who were followed up for a mean of nearly 8 years. After the exclusion of cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among patients with Crohn’s disease (SIR 1.3) and 2,331 occurred among patients with ulcerative colitis (SIR 1.1). Diagnosis of Crohn’s disease was weakly associated with gastrointestinal cancers (SIR 1.2) and extraintestinal cancers (SIR 1.3), with the strongest associations for hematologic malignancies (SIR 1.9), smoking-related cancers (SIR 1.5), and melanoma (SIR 1.4). Associations between ulcerative colitis and gastrointestinal and extraintestinal cancers were weaker (SIR of 1.1 for both).

The excess risk of cancer in patients with Crohn’s disease "largely is owing to extraintestinal cancers, particularly hematologic malignancies and melanoma, both of which may be related to immune suppression, and smoking-related cancers," the researchers concluded. They added that their study "provides reassuring data that the decreasing risk for gastrointestinal malignancy observed here ... has not been offset by a concomitant increase in the risk of extraintestinal or hematologic malignancies. These findings suggest that changes in the medical and surgical treatment of IBD and/or other secular trends have not substantially impacted cancer relative risk on a population basis."

The study was supported in part by grants from the National Institute for Diabetes and Digestive and Kidney Diseases, the Karen Elise Jensen Foundation, and the Clinical Epidemiological Research Foundation.

In the second study from the journal, researchers led by Dr. Suddharth Singh of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn., conducted a systematic literature search through March 2013 for cohort studies showing incident melanoma after IBD diagnosis and an estimate of incident rate ratio or standardized incidence rate. Case reports or case series were excluded (doi: 10.1016/j.cgh.2013.04.033).

Of the 838 studies identified, 12 that comprised 172,837 patients with IBD were included in the final analysis. The pooled crude incidence rate of melanoma among patients in the 12 studies was 27.7/100,000 person-years. This translated into a 37% increase in the risk of melanoma (risk ratio of 1.37). The increase was observed independently in the patients with Crohn’s disease (RR 1.51) and in those with ulcerative colitis (RR 1.23). In addition, the risk of melanoma was higher in studies conducted prior to 1998, when biologic therapies were introduced (RR 1.52), but not in those conducted after 1998 (RR 1.08).

"The risk of melanoma has been shown to be increased in immunosuppressed patients, including patients with a prior solid organ transplant, lymphoma, and patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. It is possible that the increased risk of melanoma observed in patients with IBD may be related to underlying immune dysfunction in these patients, resulting in altered tumor surveillance" the researchers wrote.

They hypothesized that immunosuppressive medications may increase the risk of melanoma by "down-regulation of the tumor surveillance mechanisms, increased susceptibility to infection with oncogenic viruses such as melanoma-associated retroviruses, or through direct pharmacologic effects of medications on DNA metabolism. Although thiopurine analogs have been associated with an increased risk of nonmelanoma skin cancers, our pooled analysis did not suggest an increased risk of melanoma, albeit there were a limited number of studies."

Dr. Singh and his associates acknowledged certain limitations of the analysis, including the potential for misclassification bias in the included studies and the fact that studies "did not adjust for known risk factors for melanoma, including personal history of nonmelanoma skin cancers, family history of melanoma, or sun exposure."

For the meta-analysis, one author, Dr. Edward V. Loftus, disclosed that he has consulted for and has received research support from Janssen Biotech, Abbott Laboratories, and UCB Pharma. The others had no relevant conflicts to disclose.

[email protected]

Immunosuppressive therapies for inflammatory bowel disease do not appear to be implicated in the increased risk for melanomas and hematologic malignancies seen in these patients, based on the results of a large database analysis and a separate meta-analysis published in the February edition of Clinical Gastroenterology and Hepatology.

The first study, based on a nationwide population-based cohort analysis conducted in Denmark, found that patients with inflammatory bowel disease (IBD) are at increased risk for cancer, in particular hematologic malignancies and melanoma at standardized incidence ratios of 1.9 and 1.4, respectively.

The second study, based on a systematic review and meta-analysis of the medical literature, found a diagnosis of Crohn’s disease or ulcerative colitis was associated with a 37% increase in the risk of developing melanoma. Melanoma risk was higher in studies performed before the introduction of biologic therapies in 1998, but not in those studies performed after 1998.

For the first study, researchers led by Dr. Michael D. Kappelman of the division of pediatric gastroenterology at the University of North Carolina at Chapel Hill used health care databases to identify patients in Denmark with a diagnosis of Crohn’s disease or ulcerative colitis from 1978 through 2010 (doi: 10.1016/j.cgh.2013.03.034). They followed the patients until the first occurrence of cancer, death, or emigration and used standardized incidence ratios (SIRs) to compare cancer incidence in patients with IBD with that expected in the general population.

"If immunosuppressive medications reduce the risk of gastrointestinal malignancy by suppressing intestinal inflammation but increase the risk of extraintestinal malignancies, IBD patients may be trading off one set of risks for another," the researchers wrote. "We therefore sought to evaluate both intestinal and extraintestinal malignancies comprehensively, as well as the occurrence of any invasive cancer, in a nationwide cohort of patients with IBD in Denmark."

The analysis included 13,756 patients with Crohn’s disease and 35,152 patients with ulcerative colitis who were followed up for a mean of nearly 8 years. After the exclusion of cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among patients with Crohn’s disease (SIR 1.3) and 2,331 occurred among patients with ulcerative colitis (SIR 1.1). Diagnosis of Crohn’s disease was weakly associated with gastrointestinal cancers (SIR 1.2) and extraintestinal cancers (SIR 1.3), with the strongest associations for hematologic malignancies (SIR 1.9), smoking-related cancers (SIR 1.5), and melanoma (SIR 1.4). Associations between ulcerative colitis and gastrointestinal and extraintestinal cancers were weaker (SIR of 1.1 for both).

The excess risk of cancer in patients with Crohn’s disease "largely is owing to extraintestinal cancers, particularly hematologic malignancies and melanoma, both of which may be related to immune suppression, and smoking-related cancers," the researchers concluded. They added that their study "provides reassuring data that the decreasing risk for gastrointestinal malignancy observed here ... has not been offset by a concomitant increase in the risk of extraintestinal or hematologic malignancies. These findings suggest that changes in the medical and surgical treatment of IBD and/or other secular trends have not substantially impacted cancer relative risk on a population basis."

The study was supported in part by grants from the National Institute for Diabetes and Digestive and Kidney Diseases, the Karen Elise Jensen Foundation, and the Clinical Epidemiological Research Foundation.

In the second study from the journal, researchers led by Dr. Suddharth Singh of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn., conducted a systematic literature search through March 2013 for cohort studies showing incident melanoma after IBD diagnosis and an estimate of incident rate ratio or standardized incidence rate. Case reports or case series were excluded (doi: 10.1016/j.cgh.2013.04.033).

Of the 838 studies identified, 12 that comprised 172,837 patients with IBD were included in the final analysis. The pooled crude incidence rate of melanoma among patients in the 12 studies was 27.7/100,000 person-years. This translated into a 37% increase in the risk of melanoma (risk ratio of 1.37). The increase was observed independently in the patients with Crohn’s disease (RR 1.51) and in those with ulcerative colitis (RR 1.23). In addition, the risk of melanoma was higher in studies conducted prior to 1998, when biologic therapies were introduced (RR 1.52), but not in those conducted after 1998 (RR 1.08).

"The risk of melanoma has been shown to be increased in immunosuppressed patients, including patients with a prior solid organ transplant, lymphoma, and patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. It is possible that the increased risk of melanoma observed in patients with IBD may be related to underlying immune dysfunction in these patients, resulting in altered tumor surveillance" the researchers wrote.

They hypothesized that immunosuppressive medications may increase the risk of melanoma by "down-regulation of the tumor surveillance mechanisms, increased susceptibility to infection with oncogenic viruses such as melanoma-associated retroviruses, or through direct pharmacologic effects of medications on DNA metabolism. Although thiopurine analogs have been associated with an increased risk of nonmelanoma skin cancers, our pooled analysis did not suggest an increased risk of melanoma, albeit there were a limited number of studies."

Dr. Singh and his associates acknowledged certain limitations of the analysis, including the potential for misclassification bias in the included studies and the fact that studies "did not adjust for known risk factors for melanoma, including personal history of nonmelanoma skin cancers, family history of melanoma, or sun exposure."

For the meta-analysis, one author, Dr. Edward V. Loftus, disclosed that he has consulted for and has received research support from Janssen Biotech, Abbott Laboratories, and UCB Pharma. The others had no relevant conflicts to disclose.

[email protected]

Immunosuppressive therapies for inflammatory bowel disease do not appear to be implicated in the increased risk for melanomas and hematologic malignancies seen in these patients, based on the results of a large database analysis and a separate meta-analysis published in the February edition of Clinical Gastroenterology and Hepatology.

The first study, based on a nationwide population-based cohort analysis conducted in Denmark, found that patients with inflammatory bowel disease (IBD) are at increased risk for cancer, in particular hematologic malignancies and melanoma at standardized incidence ratios of 1.9 and 1.4, respectively.

The second study, based on a systematic review and meta-analysis of the medical literature, found a diagnosis of Crohn’s disease or ulcerative colitis was associated with a 37% increase in the risk of developing melanoma. Melanoma risk was higher in studies performed before the introduction of biologic therapies in 1998, but not in those studies performed after 1998.

For the first study, researchers led by Dr. Michael D. Kappelman of the division of pediatric gastroenterology at the University of North Carolina at Chapel Hill used health care databases to identify patients in Denmark with a diagnosis of Crohn’s disease or ulcerative colitis from 1978 through 2010 (doi: 10.1016/j.cgh.2013.03.034). They followed the patients until the first occurrence of cancer, death, or emigration and used standardized incidence ratios (SIRs) to compare cancer incidence in patients with IBD with that expected in the general population.

"If immunosuppressive medications reduce the risk of gastrointestinal malignancy by suppressing intestinal inflammation but increase the risk of extraintestinal malignancies, IBD patients may be trading off one set of risks for another," the researchers wrote. "We therefore sought to evaluate both intestinal and extraintestinal malignancies comprehensively, as well as the occurrence of any invasive cancer, in a nationwide cohort of patients with IBD in Denmark."

The analysis included 13,756 patients with Crohn’s disease and 35,152 patients with ulcerative colitis who were followed up for a mean of nearly 8 years. After the exclusion of cancers diagnosed within 1 year of IBD diagnosis, 772 cases of invasive cancer occurred among patients with Crohn’s disease (SIR 1.3) and 2,331 occurred among patients with ulcerative colitis (SIR 1.1). Diagnosis of Crohn’s disease was weakly associated with gastrointestinal cancers (SIR 1.2) and extraintestinal cancers (SIR 1.3), with the strongest associations for hematologic malignancies (SIR 1.9), smoking-related cancers (SIR 1.5), and melanoma (SIR 1.4). Associations between ulcerative colitis and gastrointestinal and extraintestinal cancers were weaker (SIR of 1.1 for both).

The excess risk of cancer in patients with Crohn’s disease "largely is owing to extraintestinal cancers, particularly hematologic malignancies and melanoma, both of which may be related to immune suppression, and smoking-related cancers," the researchers concluded. They added that their study "provides reassuring data that the decreasing risk for gastrointestinal malignancy observed here ... has not been offset by a concomitant increase in the risk of extraintestinal or hematologic malignancies. These findings suggest that changes in the medical and surgical treatment of IBD and/or other secular trends have not substantially impacted cancer relative risk on a population basis."

The study was supported in part by grants from the National Institute for Diabetes and Digestive and Kidney Diseases, the Karen Elise Jensen Foundation, and the Clinical Epidemiological Research Foundation.

In the second study from the journal, researchers led by Dr. Suddharth Singh of the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn., conducted a systematic literature search through March 2013 for cohort studies showing incident melanoma after IBD diagnosis and an estimate of incident rate ratio or standardized incidence rate. Case reports or case series were excluded (doi: 10.1016/j.cgh.2013.04.033).

Of the 838 studies identified, 12 that comprised 172,837 patients with IBD were included in the final analysis. The pooled crude incidence rate of melanoma among patients in the 12 studies was 27.7/100,000 person-years. This translated into a 37% increase in the risk of melanoma (risk ratio of 1.37). The increase was observed independently in the patients with Crohn’s disease (RR 1.51) and in those with ulcerative colitis (RR 1.23). In addition, the risk of melanoma was higher in studies conducted prior to 1998, when biologic therapies were introduced (RR 1.52), but not in those conducted after 1998 (RR 1.08).

"The risk of melanoma has been shown to be increased in immunosuppressed patients, including patients with a prior solid organ transplant, lymphoma, and patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. It is possible that the increased risk of melanoma observed in patients with IBD may be related to underlying immune dysfunction in these patients, resulting in altered tumor surveillance" the researchers wrote.

They hypothesized that immunosuppressive medications may increase the risk of melanoma by "down-regulation of the tumor surveillance mechanisms, increased susceptibility to infection with oncogenic viruses such as melanoma-associated retroviruses, or through direct pharmacologic effects of medications on DNA metabolism. Although thiopurine analogs have been associated with an increased risk of nonmelanoma skin cancers, our pooled analysis did not suggest an increased risk of melanoma, albeit there were a limited number of studies."

Dr. Singh and his associates acknowledged certain limitations of the analysis, including the potential for misclassification bias in the included studies and the fact that studies "did not adjust for known risk factors for melanoma, including personal history of nonmelanoma skin cancers, family history of melanoma, or sun exposure."

For the meta-analysis, one author, Dr. Edward V. Loftus, disclosed that he has consulted for and has received research support from Janssen Biotech, Abbott Laboratories, and UCB Pharma. The others had no relevant conflicts to disclose.

[email protected]

Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols reduced functional gastrointestinal symptoms in patients with irritable bowel syndrome.

The finding, published by Dr. Emma P. Halmos in the January issue of Gastroenterology (2013; [doi:10.1053/j.gastro.2013.09.046]), confirms that the diet’s "growing popularity" is warranted, and supports its use as a first-line therapy for IBS.

Dr. Halmos of Monash University, in Box Hill, Australia, and her colleagues looked at 30 patients with IBS and 8 healthy controls.

At baseline, all patients recorded their normal, daily dietary intake in a food diary for 1 week, as well as IBS symptoms.

Patients were then randomized to receive either 21 days’ worth of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), meaning less than or equal to 5 grams per sitting of these ingredients, or food representing a typical Australian diet.

For example, instead of a breakfast of "wheat biscuit–type cereal with 1/2 cup lactose-free milk, two slices wheat toast," the low-FODMAP adherents were given one cup corn flakes with 1/2 cup lactose-free milk and two slices of spelt toast.

Almost all food was provided, including three main meals and three snacks daily.

Next, there was a washout period during which each participant resumed their usual diet and then crossed-over to the alternate, which was not begun until the symptoms had returned to the same level as baseline.

Patients were prohibited from taking any other therapies for IBS during the study period, nor were they permitted to take any pharmacologic agents to alter their symptoms, including laxatives or antidiarrheals.

At baseline, the mean overall gastrointestinal symptoms score for IBS patients was 36.0 mm on the Visual Analogue Scale.

By the final 14 days of the intervention, IBS patients on the low-FODMAP diet reported a mean overall symptom score of 22.8 mm (P less than .001, compared with baseline).

That was in contrast to the 44.9 mm among IBS patients on the typical Australian diet (P less than .001, compared with baseline), with the difference between the two scores also reaching statistical significance (P less than .001).

Moreover, 21 of 30 IBS patients reported improvements of 10 mm or more on the low-FODMAP diet, wrote the authors.

Healthy controls, meanwhile, had very low scores at baseline (17.8 mm), and there was no change in symptoms on the low-FODMAP or typical Australian diets.

The authors also assessed adherence, as recorded in food diaries. IBS patients were adherent for a median 41 of the 42 days of the combined diets, and healthy controls were adherent for the entire 42 days.

Additionally, "If adherence for at least 17 days of the 21 days of controlled diet (greater than 81% of the days) was arbitrarily considered compliant, then all participants were adherent to the typical Australian diet, and 80% of IBS participants (24 of 30) and 100% of healthy controls were adherent to the low-FODMAP diet," wrote the authors.

According to the authors, one of the strengths of this study was in comparing the low-FODMAP diet with a typical Australian diet, as opposed to an intentionally very-high FODMAP regimen, as earlier studies have done.

They added that providing almost all food to participants facilitated a high degree of adherence.

However, "In life, the low-FODMAP diet is dietitian taught. Dietary restriction would have more varying degrees of compliance and depend on the patients’ degree of understanding, food choices, and motivation for altering dietary habits, as well as the dietitians’ advice on level of FODMAP restriction required," they wrote.

Dr. Halmos disclosed that two coauthors have previously published books on food intolerances and a low-FODMAP diet. They wrote that the study was supported by the National Health and Medical Research Council of Australia, the Les and Eva Erdi Foundation, and by a scholarship from Monash University.

Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols reduced functional gastrointestinal symptoms in patients with irritable bowel syndrome.

The finding, published by Dr. Emma P. Halmos in the January issue of Gastroenterology (2013; [doi:10.1053/j.gastro.2013.09.046]), confirms that the diet’s "growing popularity" is warranted, and supports its use as a first-line therapy for IBS.

Dr. Halmos of Monash University, in Box Hill, Australia, and her colleagues looked at 30 patients with IBS and 8 healthy controls.

At baseline, all patients recorded their normal, daily dietary intake in a food diary for 1 week, as well as IBS symptoms.

Patients were then randomized to receive either 21 days’ worth of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), meaning less than or equal to 5 grams per sitting of these ingredients, or food representing a typical Australian diet.

For example, instead of a breakfast of "wheat biscuit–type cereal with 1/2 cup lactose-free milk, two slices wheat toast," the low-FODMAP adherents were given one cup corn flakes with 1/2 cup lactose-free milk and two slices of spelt toast.

Almost all food was provided, including three main meals and three snacks daily.

Next, there was a washout period during which each participant resumed their usual diet and then crossed-over to the alternate, which was not begun until the symptoms had returned to the same level as baseline.

Patients were prohibited from taking any other therapies for IBS during the study period, nor were they permitted to take any pharmacologic agents to alter their symptoms, including laxatives or antidiarrheals.

At baseline, the mean overall gastrointestinal symptoms score for IBS patients was 36.0 mm on the Visual Analogue Scale.

By the final 14 days of the intervention, IBS patients on the low-FODMAP diet reported a mean overall symptom score of 22.8 mm (P less than .001, compared with baseline).

That was in contrast to the 44.9 mm among IBS patients on the typical Australian diet (P less than .001, compared with baseline), with the difference between the two scores also reaching statistical significance (P less than .001).

Moreover, 21 of 30 IBS patients reported improvements of 10 mm or more on the low-FODMAP diet, wrote the authors.

Healthy controls, meanwhile, had very low scores at baseline (17.8 mm), and there was no change in symptoms on the low-FODMAP or typical Australian diets.

The authors also assessed adherence, as recorded in food diaries. IBS patients were adherent for a median 41 of the 42 days of the combined diets, and healthy controls were adherent for the entire 42 days.

Additionally, "If adherence for at least 17 days of the 21 days of controlled diet (greater than 81% of the days) was arbitrarily considered compliant, then all participants were adherent to the typical Australian diet, and 80% of IBS participants (24 of 30) and 100% of healthy controls were adherent to the low-FODMAP diet," wrote the authors.

According to the authors, one of the strengths of this study was in comparing the low-FODMAP diet with a typical Australian diet, as opposed to an intentionally very-high FODMAP regimen, as earlier studies have done.

They added that providing almost all food to participants facilitated a high degree of adherence.

However, "In life, the low-FODMAP diet is dietitian taught. Dietary restriction would have more varying degrees of compliance and depend on the patients’ degree of understanding, food choices, and motivation for altering dietary habits, as well as the dietitians’ advice on level of FODMAP restriction required," they wrote.

Dr. Halmos disclosed that two coauthors have previously published books on food intolerances and a low-FODMAP diet. They wrote that the study was supported by the National Health and Medical Research Council of Australia, the Les and Eva Erdi Foundation, and by a scholarship from Monash University.

Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols reduced functional gastrointestinal symptoms in patients with irritable bowel syndrome.

The finding, published by Dr. Emma P. Halmos in the January issue of Gastroenterology (2013; [doi:10.1053/j.gastro.2013.09.046]), confirms that the diet’s "growing popularity" is warranted, and supports its use as a first-line therapy for IBS.

Dr. Halmos of Monash University, in Box Hill, Australia, and her colleagues looked at 30 patients with IBS and 8 healthy controls.

At baseline, all patients recorded their normal, daily dietary intake in a food diary for 1 week, as well as IBS symptoms.

Patients were then randomized to receive either 21 days’ worth of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), meaning less than or equal to 5 grams per sitting of these ingredients, or food representing a typical Australian diet.

For example, instead of a breakfast of "wheat biscuit–type cereal with 1/2 cup lactose-free milk, two slices wheat toast," the low-FODMAP adherents were given one cup corn flakes with 1/2 cup lactose-free milk and two slices of spelt toast.

Almost all food was provided, including three main meals and three snacks daily.

Next, there was a washout period during which each participant resumed their usual diet and then crossed-over to the alternate, which was not begun until the symptoms had returned to the same level as baseline.

Patients were prohibited from taking any other therapies for IBS during the study period, nor were they permitted to take any pharmacologic agents to alter their symptoms, including laxatives or antidiarrheals.

At baseline, the mean overall gastrointestinal symptoms score for IBS patients was 36.0 mm on the Visual Analogue Scale.

By the final 14 days of the intervention, IBS patients on the low-FODMAP diet reported a mean overall symptom score of 22.8 mm (P less than .001, compared with baseline).

That was in contrast to the 44.9 mm among IBS patients on the typical Australian diet (P less than .001, compared with baseline), with the difference between the two scores also reaching statistical significance (P less than .001).

Moreover, 21 of 30 IBS patients reported improvements of 10 mm or more on the low-FODMAP diet, wrote the authors.

Healthy controls, meanwhile, had very low scores at baseline (17.8 mm), and there was no change in symptoms on the low-FODMAP or typical Australian diets.

The authors also assessed adherence, as recorded in food diaries. IBS patients were adherent for a median 41 of the 42 days of the combined diets, and healthy controls were adherent for the entire 42 days.

Additionally, "If adherence for at least 17 days of the 21 days of controlled diet (greater than 81% of the days) was arbitrarily considered compliant, then all participants were adherent to the typical Australian diet, and 80% of IBS participants (24 of 30) and 100% of healthy controls were adherent to the low-FODMAP diet," wrote the authors.

According to the authors, one of the strengths of this study was in comparing the low-FODMAP diet with a typical Australian diet, as opposed to an intentionally very-high FODMAP regimen, as earlier studies have done.

They added that providing almost all food to participants facilitated a high degree of adherence.

However, "In life, the low-FODMAP diet is dietitian taught. Dietary restriction would have more varying degrees of compliance and depend on the patients’ degree of understanding, food choices, and motivation for altering dietary habits, as well as the dietitians’ advice on level of FODMAP restriction required," they wrote.

Dr. Halmos disclosed that two coauthors have previously published books on food intolerances and a low-FODMAP diet. They wrote that the study was supported by the National Health and Medical Research Council of Australia, the Les and Eva Erdi Foundation, and by a scholarship from Monash University.

Subcutaneous golimumab induces and maintains clinical response in ulcerative colitis, according to two studies in the January issue of Gastroenterology.

In the first, Dr. William J. Sandborn of the University of California San Diego, and his colleagues, looked at 1,064 patients enrolled in the PURSUIT-SC study (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment–Subcutaneous), an integrated phase II and phase III study of subcutaneous golimumab.

Golimumab, developed by Janssen Pharmaceutical Companies of Johnson & Johnson – the sponsor of both studies in this month’s Gastroenterology – is a fully human monoclonal antibody to tumor necrosis factor–alpha.

All patients had an established diagnosis of UC and moderate to severe disease activity, defined as a Mayo score of 6-12, with an endoscopic subscore of at least 2.

Additionally, all patients had previously tried and failed oral 5-aminosalicylates, oral corticosteroids, azathioprine (AZA), and/or 6-mercaptopurine. Alternatively, they were simply unable to wean off corticosteroids.

Patients enrolled in the phase II, dose-finding portion of the study were randomized to subcutaneous injections of placebo or one of three different golimumab doses at weeks 0 and 2: 100/50 mg (i.e., 100 mg at week 0 and 50 mg at week 2), 200/100 mg, or 400/200 mg, respectively (n = 169).

"An additional 122 patients were enrolled while phase II data were being analyzed," wrote the authors.

"Clinical response" was defined as a decrease from baseline in the Mayo score of at least 30% and 3 or more points, accompanied by either a rectal bleeding subscore of 0 or 1, or a decrease from baseline in the rectal bleeding subscore of at least 1.

"Clinical remission" was defined as a Mayo score less than or equal to 2, with no individual subscore greater than 1.

Finally, "mucosal healing" was defined as a Mayo endoscopy subscore of 0 or 1.

The authors found that the median changes from the baseline Mayo score were –1.0, –3.0, –2.0, and –3.0 for placebo and golimumab 100/50 mg, 200/100 mg, and 400/200 mg, respectively.

Moreover, at week 6, a numerically greater proportion of patients assigned to golimumab 400/200 mg were in clinical response or remission, had mucosal healing, or had Inflammatory Bowel Disease Questionnaire (IBDQ) scores superior to that of placebo patients.

Next, after analysis of the dose-finding data, the 200/100–mg and 400/200–mg doses were selected for evaluation in phase III, a dose confirmation trial.

Overall, 774 patients participated in this portion of the trial, randomized to placebo, golimumab 200/100 mg, or 400/200 mg at weeks 0 and 2.

By week 6, significantly greater proportions of patients in the golimumab 200/100–mg and golimumab 400/200–mg groups (51.0%, and 54.9%, respectively) were in clinical response compared with patients assigned to placebo (30.3%; P less than 0.0001 for both comparisons).

"The efficacy of both golimumab induction regimens was also demonstrated for the major secondary endpoints of clinical remission, mucosal healing, and improvement from baseline in the IBDQ score, all at week 6," they added.

Looking at safety, nearly 40% of all phase III cohorts reported adverse events, most commonly headache and nasopharyngitis.

The most common serious adverse event – exacerbation of UC – was reported by 8 (1.1%) golimumab-treated and 8 (2.4%) placebo-treated patients.

A second study, also led by Dr. Sandborn, looked at whether continuous golimumab dosing would result in remission maintained to 1 year.

To that end, Dr. Sandborn next randomized the golimumab initial responders in the first study (n = 464) to placebo or injections of 50 or 100 mg golimumab every 4 weeks through 1 year.

Overall, 49.7% of patients in the 100-mg cohort maintained a clinical response through week 54, compared with 47% in the 50-mg group and 31.2% in the placebo group (P less than .001 and P = .010 for each dose versus placebo, respectively).

Remission was also seen with greater frequency among patients receiving 100 mg golimumab at both 30 and 54 weeks (27.8%) compared with placebo (15.6%; P = .004).

Finally, the proportion of patients with mucosal healing at both weeks 30 and 54 was significantly greater for patients receiving golimumab 100 mg (42.4%) compared with placebo (26.6%; P = .002). The mucosal healing rate for the 50-mg golimumab cohort was 41.7%.

Looking at safety, the authors did concede that "the proportions of patients who experienced at least one serious adverse event or discontinued because of an adverse event were greater for golimumab 100 mg compared with placebo or golimumab 50 mg."

However, "the duration of follow-up evaluation in the placebo group was notably shorter than either of the golimumab groups, and when adjusted for follow-up time, difference in the incidences of serious adverse events per 100 patient-years were less remarkable across treatment groups."

Dr. Sandborn and colleagues disclosed ties with Janssen Research and Development, which sponsored the studies. Janssen Biotech is the maker of golimumab.

Subcutaneous golimumab induces and maintains clinical response in ulcerative colitis, according to two studies in the January issue of Gastroenterology.

In the first, Dr. William J. Sandborn of the University of California San Diego, and his colleagues, looked at 1,064 patients enrolled in the PURSUIT-SC study (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment–Subcutaneous), an integrated phase II and phase III study of subcutaneous golimumab.

Golimumab, developed by Janssen Pharmaceutical Companies of Johnson & Johnson – the sponsor of both studies in this month’s Gastroenterology – is a fully human monoclonal antibody to tumor necrosis factor–alpha.

All patients had an established diagnosis of UC and moderate to severe disease activity, defined as a Mayo score of 6-12, with an endoscopic subscore of at least 2.

Additionally, all patients had previously tried and failed oral 5-aminosalicylates, oral corticosteroids, azathioprine (AZA), and/or 6-mercaptopurine. Alternatively, they were simply unable to wean off corticosteroids.

Patients enrolled in the phase II, dose-finding portion of the study were randomized to subcutaneous injections of placebo or one of three different golimumab doses at weeks 0 and 2: 100/50 mg (i.e., 100 mg at week 0 and 50 mg at week 2), 200/100 mg, or 400/200 mg, respectively (n = 169).

"An additional 122 patients were enrolled while phase II data were being analyzed," wrote the authors.

"Clinical response" was defined as a decrease from baseline in the Mayo score of at least 30% and 3 or more points, accompanied by either a rectal bleeding subscore of 0 or 1, or a decrease from baseline in the rectal bleeding subscore of at least 1.

"Clinical remission" was defined as a Mayo score less than or equal to 2, with no individual subscore greater than 1.

Finally, "mucosal healing" was defined as a Mayo endoscopy subscore of 0 or 1.

The authors found that the median changes from the baseline Mayo score were –1.0, –3.0, –2.0, and –3.0 for placebo and golimumab 100/50 mg, 200/100 mg, and 400/200 mg, respectively.

Moreover, at week 6, a numerically greater proportion of patients assigned to golimumab 400/200 mg were in clinical response or remission, had mucosal healing, or had Inflammatory Bowel Disease Questionnaire (IBDQ) scores superior to that of placebo patients.

Next, after analysis of the dose-finding data, the 200/100–mg and 400/200–mg doses were selected for evaluation in phase III, a dose confirmation trial.

Overall, 774 patients participated in this portion of the trial, randomized to placebo, golimumab 200/100 mg, or 400/200 mg at weeks 0 and 2.

By week 6, significantly greater proportions of patients in the golimumab 200/100–mg and golimumab 400/200–mg groups (51.0%, and 54.9%, respectively) were in clinical response compared with patients assigned to placebo (30.3%; P less than 0.0001 for both comparisons).

"The efficacy of both golimumab induction regimens was also demonstrated for the major secondary endpoints of clinical remission, mucosal healing, and improvement from baseline in the IBDQ score, all at week 6," they added.

Looking at safety, nearly 40% of all phase III cohorts reported adverse events, most commonly headache and nasopharyngitis.

The most common serious adverse event – exacerbation of UC – was reported by 8 (1.1%) golimumab-treated and 8 (2.4%) placebo-treated patients.

A second study, also led by Dr. Sandborn, looked at whether continuous golimumab dosing would result in remission maintained to 1 year.

To that end, Dr. Sandborn next randomized the golimumab initial responders in the first study (n = 464) to placebo or injections of 50 or 100 mg golimumab every 4 weeks through 1 year.

Overall, 49.7% of patients in the 100-mg cohort maintained a clinical response through week 54, compared with 47% in the 50-mg group and 31.2% in the placebo group (P less than .001 and P = .010 for each dose versus placebo, respectively).

Remission was also seen with greater frequency among patients receiving 100 mg golimumab at both 30 and 54 weeks (27.8%) compared with placebo (15.6%; P = .004).

Finally, the proportion of patients with mucosal healing at both weeks 30 and 54 was significantly greater for patients receiving golimumab 100 mg (42.4%) compared with placebo (26.6%; P = .002). The mucosal healing rate for the 50-mg golimumab cohort was 41.7%.

Looking at safety, the authors did concede that "the proportions of patients who experienced at least one serious adverse event or discontinued because of an adverse event were greater for golimumab 100 mg compared with placebo or golimumab 50 mg."

However, "the duration of follow-up evaluation in the placebo group was notably shorter than either of the golimumab groups, and when adjusted for follow-up time, difference in the incidences of serious adverse events per 100 patient-years were less remarkable across treatment groups."

Dr. Sandborn and colleagues disclosed ties with Janssen Research and Development, which sponsored the studies. Janssen Biotech is the maker of golimumab.

Subcutaneous golimumab induces and maintains clinical response in ulcerative colitis, according to two studies in the January issue of Gastroenterology.

In the first, Dr. William J. Sandborn of the University of California San Diego, and his colleagues, looked at 1,064 patients enrolled in the PURSUIT-SC study (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment–Subcutaneous), an integrated phase II and phase III study of subcutaneous golimumab.

Golimumab, developed by Janssen Pharmaceutical Companies of Johnson & Johnson – the sponsor of both studies in this month’s Gastroenterology – is a fully human monoclonal antibody to tumor necrosis factor–alpha.

All patients had an established diagnosis of UC and moderate to severe disease activity, defined as a Mayo score of 6-12, with an endoscopic subscore of at least 2.

Additionally, all patients had previously tried and failed oral 5-aminosalicylates, oral corticosteroids, azathioprine (AZA), and/or 6-mercaptopurine. Alternatively, they were simply unable to wean off corticosteroids.

Patients enrolled in the phase II, dose-finding portion of the study were randomized to subcutaneous injections of placebo or one of three different golimumab doses at weeks 0 and 2: 100/50 mg (i.e., 100 mg at week 0 and 50 mg at week 2), 200/100 mg, or 400/200 mg, respectively (n = 169).

"An additional 122 patients were enrolled while phase II data were being analyzed," wrote the authors.

"Clinical response" was defined as a decrease from baseline in the Mayo score of at least 30% and 3 or more points, accompanied by either a rectal bleeding subscore of 0 or 1, or a decrease from baseline in the rectal bleeding subscore of at least 1.

"Clinical remission" was defined as a Mayo score less than or equal to 2, with no individual subscore greater than 1.

Finally, "mucosal healing" was defined as a Mayo endoscopy subscore of 0 or 1.

The authors found that the median changes from the baseline Mayo score were –1.0, –3.0, –2.0, and –3.0 for placebo and golimumab 100/50 mg, 200/100 mg, and 400/200 mg, respectively.

Moreover, at week 6, a numerically greater proportion of patients assigned to golimumab 400/200 mg were in clinical response or remission, had mucosal healing, or had Inflammatory Bowel Disease Questionnaire (IBDQ) scores superior to that of placebo patients.

Next, after analysis of the dose-finding data, the 200/100–mg and 400/200–mg doses were selected for evaluation in phase III, a dose confirmation trial.

Overall, 774 patients participated in this portion of the trial, randomized to placebo, golimumab 200/100 mg, or 400/200 mg at weeks 0 and 2.

By week 6, significantly greater proportions of patients in the golimumab 200/100–mg and golimumab 400/200–mg groups (51.0%, and 54.9%, respectively) were in clinical response compared with patients assigned to placebo (30.3%; P less than 0.0001 for both comparisons).

"The efficacy of both golimumab induction regimens was also demonstrated for the major secondary endpoints of clinical remission, mucosal healing, and improvement from baseline in the IBDQ score, all at week 6," they added.

Looking at safety, nearly 40% of all phase III cohorts reported adverse events, most commonly headache and nasopharyngitis.

The most common serious adverse event – exacerbation of UC – was reported by 8 (1.1%) golimumab-treated and 8 (2.4%) placebo-treated patients.

A second study, also led by Dr. Sandborn, looked at whether continuous golimumab dosing would result in remission maintained to 1 year.

To that end, Dr. Sandborn next randomized the golimumab initial responders in the first study (n = 464) to placebo or injections of 50 or 100 mg golimumab every 4 weeks through 1 year.

Overall, 49.7% of patients in the 100-mg cohort maintained a clinical response through week 54, compared with 47% in the 50-mg group and 31.2% in the placebo group (P less than .001 and P = .010 for each dose versus placebo, respectively).

Remission was also seen with greater frequency among patients receiving 100 mg golimumab at both 30 and 54 weeks (27.8%) compared with placebo (15.6%; P = .004).

Finally, the proportion of patients with mucosal healing at both weeks 30 and 54 was significantly greater for patients receiving golimumab 100 mg (42.4%) compared with placebo (26.6%; P = .002). The mucosal healing rate for the 50-mg golimumab cohort was 41.7%.

Looking at safety, the authors did concede that "the proportions of patients who experienced at least one serious adverse event or discontinued because of an adverse event were greater for golimumab 100 mg compared with placebo or golimumab 50 mg."

However, "the duration of follow-up evaluation in the placebo group was notably shorter than either of the golimumab groups, and when adjusted for follow-up time, difference in the incidences of serious adverse events per 100 patient-years were less remarkable across treatment groups."

Dr. Sandborn and colleagues disclosed ties with Janssen Research and Development, which sponsored the studies. Janssen Biotech is the maker of golimumab.

Bisphosphonates are safe and effective for treating low bone mineral density in inflammatory bowel disease, according to a meta-analysis of 19 randomized controlled studies published in the January issue of Clinical Gastroenterology and Hepatology.

On the other hand, alternative therapies such as calcium plus vitamin D, calcitonin, and low-impact exercise demonstrated questionable efficacy, leading the authors to conclude that bisphosphonates alone "should be more aggressively considered" in this population.

Dr. John Melek of Mercy Hospital and Medical Center, Chicago, and Dr. Atsushi Sakuraba of the Inflammatory Bowel Disease Center at the University of Chicago Medicine, searched the MEDLINE and EMBASE databases as well as Google scholar, the UMIN Clinical Trials Registry, and the Cochrane Central Register for randomized controlled trials conducted between 1981 and 2011 assessing treatment for low BMD in IBD.

Overall, 11 of the 19 included studies evaluated bisphosphonates versus placebo or no treatment, while 4 looked at sodium fluoride versus placebo/no treatment, and 2 assessed calcium plus vitamin D versus placebo/no treatment.

The remaining analyses tested calcitonin versus placebo (1); low-impact exercise versus habitual physical activity (1); and bisphosphonates versus vitamin D (1) and fluoride (1). (Three studies compared multiple arms within the same study.)

Among all data on bisphosphonate efficacy, the authors found that the pooled overall effect by mixed-effect analysis revealed bisphosphonates to be significantly superior to control therapies in improving lumbar spine BMD, with a standard difference in means (SDm) of 0.51 (95% confidence interval [CI], 0.29-0.72; P less than .01).

Indeed, among the seven studies that reported improvements in the hip BMD, for example, a pooled overall effect by mixed-effect analysis showed that bisphosphonates were significantly superior to controls (both other treatments and no treatment; SDm, 0.26; 95% CI, 0.04-0.49; P = .02).

Moreover, among studies which reported the incidences of nonvertebral and vertebral fractures, the pooled ORs were 0.35 (95% CI, 0.06-1.95; P = .23) and 0.38 (95% CI, 0.15-0.96; P = .04), respectively.

Looking at adverse effects, meanwhile, the pooled odds ratio of adverse effects was a nonsignificant 1.24 (95% CI, 0.83-1.85; P = .29), "demonstrating that bisphosphonate treatment was not associated with an increased incidence of adverse effects."

Sodium fluoride, meanwhile, showed some efficacy: The four studies that assessed this treatment showed it was superior to placebo/no treatment in improving lumbar spine BMD (SDm, 1.18; 95% CI, 0.10-2.26; P = .03).

Fluoride did not, however, significantly improve hip BMD, compared with placebo, nor did it reduce the incidence of vertebral or nonvertebral fractures.

Similarly, the one study that looked at calcitonin (and assessed only children and adolescents with active or quiescent Crohn’s disease or ulcerative colitis, plus osteopenia or osteoporosis) found that this treatment was not superior to placebo in improving BMD at the lumbar spine. It did not find changes in hip BMD or the incidence of fractures.

Nor was low-impact exercise superior to control (habitual physical activity) in improving BMD at the hip or lumbar spine; fracture incidence was not assessed.

The authors conceded several limitations, the greatest of which was the presence of marked heterogeneity among studies, which necessitated use of the random-effects model or mixed-effect analysis. Indeed, much of this heterogeneity was due to the fact that some studies aimed to prevent bone loss, whereas others treated established osteopenia, they wrote.

Additionally, although many IBD patients are today treated with biologic therapies, few studies evaluated BMD regimens in IBD patients who underwent biologic treatment.

The authors disclosed no conflicts of interest related to this analysis. Dr. Sakuraba was supported by the Foreign Clinical Pharmacology Training Program of the Japanese Society of Clinical Pharmacology and Therapeutics.

Bisphosphonates are safe and effective for treating low bone mineral density in inflammatory bowel disease, according to a meta-analysis of 19 randomized controlled studies published in the January issue of Clinical Gastroenterology and Hepatology.

On the other hand, alternative therapies such as calcium plus vitamin D, calcitonin, and low-impact exercise demonstrated questionable efficacy, leading the authors to conclude that bisphosphonates alone "should be more aggressively considered" in this population.

Dr. John Melek of Mercy Hospital and Medical Center, Chicago, and Dr. Atsushi Sakuraba of the Inflammatory Bowel Disease Center at the University of Chicago Medicine, searched the MEDLINE and EMBASE databases as well as Google scholar, the UMIN Clinical Trials Registry, and the Cochrane Central Register for randomized controlled trials conducted between 1981 and 2011 assessing treatment for low BMD in IBD.

Overall, 11 of the 19 included studies evaluated bisphosphonates versus placebo or no treatment, while 4 looked at sodium fluoride versus placebo/no treatment, and 2 assessed calcium plus vitamin D versus placebo/no treatment.

The remaining analyses tested calcitonin versus placebo (1); low-impact exercise versus habitual physical activity (1); and bisphosphonates versus vitamin D (1) and fluoride (1). (Three studies compared multiple arms within the same study.)

Among all data on bisphosphonate efficacy, the authors found that the pooled overall effect by mixed-effect analysis revealed bisphosphonates to be significantly superior to control therapies in improving lumbar spine BMD, with a standard difference in means (SDm) of 0.51 (95% confidence interval [CI], 0.29-0.72; P less than .01).

Indeed, among the seven studies that reported improvements in the hip BMD, for example, a pooled overall effect by mixed-effect analysis showed that bisphosphonates were significantly superior to controls (both other treatments and no treatment; SDm, 0.26; 95% CI, 0.04-0.49; P = .02).

Moreover, among studies which reported the incidences of nonvertebral and vertebral fractures, the pooled ORs were 0.35 (95% CI, 0.06-1.95; P = .23) and 0.38 (95% CI, 0.15-0.96; P = .04), respectively.

Looking at adverse effects, meanwhile, the pooled odds ratio of adverse effects was a nonsignificant 1.24 (95% CI, 0.83-1.85; P = .29), "demonstrating that bisphosphonate treatment was not associated with an increased incidence of adverse effects."

Sodium fluoride, meanwhile, showed some efficacy: The four studies that assessed this treatment showed it was superior to placebo/no treatment in improving lumbar spine BMD (SDm, 1.18; 95% CI, 0.10-2.26; P = .03).

Fluoride did not, however, significantly improve hip BMD, compared with placebo, nor did it reduce the incidence of vertebral or nonvertebral fractures.

Similarly, the one study that looked at calcitonin (and assessed only children and adolescents with active or quiescent Crohn’s disease or ulcerative colitis, plus osteopenia or osteoporosis) found that this treatment was not superior to placebo in improving BMD at the lumbar spine. It did not find changes in hip BMD or the incidence of fractures.

Nor was low-impact exercise superior to control (habitual physical activity) in improving BMD at the hip or lumbar spine; fracture incidence was not assessed.

The authors conceded several limitations, the greatest of which was the presence of marked heterogeneity among studies, which necessitated use of the random-effects model or mixed-effect analysis. Indeed, much of this heterogeneity was due to the fact that some studies aimed to prevent bone loss, whereas others treated established osteopenia, they wrote.

Additionally, although many IBD patients are today treated with biologic therapies, few studies evaluated BMD regimens in IBD patients who underwent biologic treatment.

The authors disclosed no conflicts of interest related to this analysis. Dr. Sakuraba was supported by the Foreign Clinical Pharmacology Training Program of the Japanese Society of Clinical Pharmacology and Therapeutics.

Bisphosphonates are safe and effective for treating low bone mineral density in inflammatory bowel disease, according to a meta-analysis of 19 randomized controlled studies published in the January issue of Clinical Gastroenterology and Hepatology.

On the other hand, alternative therapies such as calcium plus vitamin D, calcitonin, and low-impact exercise demonstrated questionable efficacy, leading the authors to conclude that bisphosphonates alone "should be more aggressively considered" in this population.

Dr. John Melek of Mercy Hospital and Medical Center, Chicago, and Dr. Atsushi Sakuraba of the Inflammatory Bowel Disease Center at the University of Chicago Medicine, searched the MEDLINE and EMBASE databases as well as Google scholar, the UMIN Clinical Trials Registry, and the Cochrane Central Register for randomized controlled trials conducted between 1981 and 2011 assessing treatment for low BMD in IBD.

Overall, 11 of the 19 included studies evaluated bisphosphonates versus placebo or no treatment, while 4 looked at sodium fluoride versus placebo/no treatment, and 2 assessed calcium plus vitamin D versus placebo/no treatment.

The remaining analyses tested calcitonin versus placebo (1); low-impact exercise versus habitual physical activity (1); and bisphosphonates versus vitamin D (1) and fluoride (1). (Three studies compared multiple arms within the same study.)

Among all data on bisphosphonate efficacy, the authors found that the pooled overall effect by mixed-effect analysis revealed bisphosphonates to be significantly superior to control therapies in improving lumbar spine BMD, with a standard difference in means (SDm) of 0.51 (95% confidence interval [CI], 0.29-0.72; P less than .01).

Indeed, among the seven studies that reported improvements in the hip BMD, for example, a pooled overall effect by mixed-effect analysis showed that bisphosphonates were significantly superior to controls (both other treatments and no treatment; SDm, 0.26; 95% CI, 0.04-0.49; P = .02).

Moreover, among studies which reported the incidences of nonvertebral and vertebral fractures, the pooled ORs were 0.35 (95% CI, 0.06-1.95; P = .23) and 0.38 (95% CI, 0.15-0.96; P = .04), respectively.

Looking at adverse effects, meanwhile, the pooled odds ratio of adverse effects was a nonsignificant 1.24 (95% CI, 0.83-1.85; P = .29), "demonstrating that bisphosphonate treatment was not associated with an increased incidence of adverse effects."

Sodium fluoride, meanwhile, showed some efficacy: The four studies that assessed this treatment showed it was superior to placebo/no treatment in improving lumbar spine BMD (SDm, 1.18; 95% CI, 0.10-2.26; P = .03).

Fluoride did not, however, significantly improve hip BMD, compared with placebo, nor did it reduce the incidence of vertebral or nonvertebral fractures.

Similarly, the one study that looked at calcitonin (and assessed only children and adolescents with active or quiescent Crohn’s disease or ulcerative colitis, plus osteopenia or osteoporosis) found that this treatment was not superior to placebo in improving BMD at the lumbar spine. It did not find changes in hip BMD or the incidence of fractures.

Nor was low-impact exercise superior to control (habitual physical activity) in improving BMD at the hip or lumbar spine; fracture incidence was not assessed.

The authors conceded several limitations, the greatest of which was the presence of marked heterogeneity among studies, which necessitated use of the random-effects model or mixed-effect analysis. Indeed, much of this heterogeneity was due to the fact that some studies aimed to prevent bone loss, whereas others treated established osteopenia, they wrote.

Additionally, although many IBD patients are today treated with biologic therapies, few studies evaluated BMD regimens in IBD patients who underwent biologic treatment.

The authors disclosed no conflicts of interest related to this analysis. Dr. Sakuraba was supported by the Foreign Clinical Pharmacology Training Program of the Japanese Society of Clinical Pharmacology and Therapeutics.

Not only is there no link between low-fiber diets and diverticulosis, but the incidence of diverticulitis is not nearly as common as was previously believed.

Those are the conclusions of two new studies in the December issue of Clinical Gastroenterology and Hepatology, both of which challenge long-held beliefs about the causes of these conditions.

In the first study, Dr. Anne F. Peery of the University of North Carolina at Chapel Hill, and her colleagues looked at 539 patients with colonic diverticula and 1,569 controls, all culled from the Vitamin D and Calcium Polyp Prevention Study, a double-blind, placebo-controlled trial of vitamin D and/or calcium for the prevention of colonic adenomas (doi:10.1016/j.cgh.2013.06.033).

Patients with a self-reported history of diverticulosis or diverticulitis were excluded, as were cases with a history of colon resection, inflammatory bowel disease, or familial history of colon cancer. Most cases (88%) had descending or sigmoid colon diverticula, and these patients were significantly older and more likely to be male than were the controls.

According to Dr. Peery and colleagues, there was no difference between cases and controls in terms of mean dietary fiber intake (14.8 g per day versus 15.3 g per day, P = .2) and reported supplemental fiber intake (5% versus 5%, P = .7).

Nor was there any significant link when investigators compared the highest quartile of fiber intake (mean, 25 g/day) to the lowest (mean, 8 g/day) (odds ratio = 0.96; 95% confidence interval, 0.71-1.30).

Finally, the investigators found no associations between dietary fiber intake by subtype (for instance, beans, grains, fruits, and vegetables) and diverticulosis.

"Forty years ago, Dr. Neil Painter popularized the hypothesis that inadequate dietary fiber intake and constipation were the cause of sigmoid diverticulosis," wrote Dr. Peery. However, "Although the fiber hypothesis is conceptually attractive and widely accepted, it has not been rigorously examined."

And while Dr. Peery’s data were based on a food frequency questionnaire – which could be subject to measurement bias – she added that "the mean total fiber intake in the highest quartile was 25 g, versus 8 g in the lowest.

"This wide range makes it unlikely that homogeneity of intake accounts for the null association of fiber with the presence of diverticula," she wrote.

A second study by Dr. Kamyar Shahedi of the University of California Los Angeles/Veteran’s Affairs Center for Outcomes Research and Education, also sought evidence for the commonly held belief that up to 25% of patients with diverticulosis will develop diverticulitis.

Dr. Shahedi and colleagues performed a retrospective survival analysis of 2,222 patients from the Veteran’s Affairs Greater Los Angeles Healthcare System with colonic diverticulosis and a median follow-up of 6.75 years (doi:10.1016/j.cgh.2013.06.020). Patients were excluded if they had any ICD-9 code for diverticulitis or documentation of diverticulitis in the medical record notes at any point before the index date of diverticulosis.

When the researchers looked only at imaging-confirmed or surgical specimen–confirmed cases, just 23 patients (1%) developed acute diverticulitis during the study period, Dr. Shahedi found. This jumped to 95 patients (4.3%) when clinical diagnoses were also used, for an incidence of 6 cases per 1,000 patient years.

Looking at predictors for progression, the authors found that only age was related to the development of diverticulitis, with every year of age at diverticulosis detection conferring a 2.4% lower hazard of developing diverticulitis.

According to the authors, the "widely cited figures" that up to a quarter of patients with diverticulosis will develop acute diverticulitis is based on data collected before the time of routine colon screening. "Therefore, the true denominator of individuals harboring diverticulosis was not accounted for in these calculations," they concluded.

And while their retrospective study does leave room for the possibility that cases were missed, "Future series or patient registries may better standardize the definition of diverticulitis in a prospective cohort," wrote the investigators.

In the meantime, prevalence data such as these "may help to reframe discussions with patients regarding their probability of developing clinically significant diverticulitis."

However, even as these two findings change the way providers counsel patients about the cause and impact of diverticula, a third study, also in December’s issue of Clinical Gastroenterology and Hepatology, adds another wrinkle: Patients who do develop diverticulitis are at increased risk for a diagnosis of irritable bowel syndrome later on.

Dr. Erica Cohen of the VA Greater Los Angeles Healthcare System, and colleagues looked at 1,105 chart-confirmed cases of diverticulitis, identified retrospectively from the same dataset used by Dr. Shahedi (doi:10.1016/j.cgh.2013.03.007).

All cases were matched with controls seen on the same day, the mean follow-up period was 6.3 years, and patients with pre-existing IBS or functional bowel diagnoses were excluded from the study.

The primary outcome was a new IBS diagnosis after the index diverticulitis attack (for cases) or enrollment date (for controls). Ultimately, Dr. Cohen found 24 cases of newly diagnosed IBS during the study period: 20 among diverticulitis cases, and 4 among controls. That translated to a hazard ratio of 4.7 among cases compared with controls, even after adjustment for age, sex, ethnicity, race, inpatient versus outpatient status, and comorbidity score (95% CI, 1.6 –14.0; P = .006).

Dr. Cohen offered several possible explanations for the association between diverticulitis and new diagnosis of IBS.

"Inflammation may alter gastrointestinal reflexes, amplify visceral sensitivity, render the bowel more susceptible to negative effects of microbiota, and alter motility in IBS," she said.

"Another putative mechanism of chronic diverticular disease involves shifts in intestinal microbiota leading to chronic inflammation, similar to theoretical models of IBS," Dr. Cohen said.

"Future research should identify demographic and clinical predictors of post-diverticulitis irritable bowel syndrome and evaluate its incidence in prospective studies to better determine whether the link is causal or merely associative," she concluded.

Finally, a fourth study could help researchers reduce the risk of the painful inflammatory condition: Among diverticulosis patients, higher levels of serum vitamin D were associated significantly with a lower risk of diverticulitis.

In her analysis, also published in the December issue of Clinical Gastroenterology and Hepatology, Dr. Lillias H. Maguire and colleagues identified 9,116 diverticulosis patients and 922 diverticulitis patients from the Partners Healthcare Research Patient Data Registry (doi:10.1016/j.cgh.2013.07.035). All patients had at least one prediagnostic serum vitamin D level on record between 1993 and 2012.

Dr. Maguire of Massachusetts General Hospital, Boston, found that patients with uncomplicated diverticulosis had mean levels of 29.1 ng/mL, versus 25.3 ng/mL among the diverticulitis patients (P less than .0001).

A sensitivity analysis that compared the mean prediagnostic values between cases and controls who had more than one reported vitamin D level yielded similarly significant results: The mean vitamin D level of uncomplicated diverticulosis was 33.0 ng/mL, compared with 28.1 ng/mL for acute diverticulitis patients (P less than .0001), 28.8 ng/mL for complicated diverticulitis patients (P = .002), 23.9 ng/mL for surgical diverticulitis cases (P less than .0001), and 25.5 ng/mL for recurrent diverticulitis patients (P less than .0001).

Indeed, "Compared with patients with acute diverticulitis without other sequelae, patients in the subgroups who developed abscess, required surgery, or had recurrent attacks were observed to have lower prediagnostic levels of vitamin D."

These differences between diverticulitis subgroups did not reach significance except in the cohort of patients who required surgery, who had the lowest levels of all.

"Taken together with prior studies showing an inverse association of 25(OH)D and risk of colonic cancer and inflammatory bowel disease, these results highlight the potential importance of vitamin D in the maintenance of colonic health," the investigators wrote.

"Additional studies in cohorts with more detailed information on potential confounders of this association are warranted," they added.

Dr. Peery, whose study looked at fiber intake among diverticulosis patients, and her collaborators reported having no disclosures, and stated that they received funding from the National Institutes of Health.

Dr. Shahedi, who assessed the incidence of diverticulitis, disclosed that three coinvestigators are employees of Shire Pharmaceuticals, which sponsored their study. Other investigators disclosed ties to Amgen and Ironwood Pharmaceuticals.

Dr. Cohen’s coinvestigators, who studied the prevalence of IBS following diverticulitis, disclosed ties to Ironwood Pharmaceuticals, Prometheus, Takeda Pharmaceuticals, Amgen, Ritter Pharmaceuticals, and Shire. Two investigators were employees of Shire, which funded the research.

Finally, the coinvestigators of Dr. Maguire, who looked at vitamin D levels, reported ties to Shire, Bayer Health, Pfizer, Millennium Pharmaceuticals, and Pozen. They were funded by grants from the American College of Gastroenterology as well as the National Institutes of Health.

Not only is there no link between low-fiber diets and diverticulosis, but the incidence of diverticulitis is not nearly as common as was previously believed.

Those are the conclusions of two new studies in the December issue of Clinical Gastroenterology and Hepatology, both of which challenge long-held beliefs about the causes of these conditions.

In the first study, Dr. Anne F. Peery of the University of North Carolina at Chapel Hill, and her colleagues looked at 539 patients with colonic diverticula and 1,569 controls, all culled from the Vitamin D and Calcium Polyp Prevention Study, a double-blind, placebo-controlled trial of vitamin D and/or calcium for the prevention of colonic adenomas (doi:10.1016/j.cgh.2013.06.033).

Patients with a self-reported history of diverticulosis or diverticulitis were excluded, as were cases with a history of colon resection, inflammatory bowel disease, or familial history of colon cancer. Most cases (88%) had descending or sigmoid colon diverticula, and these patients were significantly older and more likely to be male than were the controls.

According to Dr. Peery and colleagues, there was no difference between cases and controls in terms of mean dietary fiber intake (14.8 g per day versus 15.3 g per day, P = .2) and reported supplemental fiber intake (5% versus 5%, P = .7).

Nor was there any significant link when investigators compared the highest quartile of fiber intake (mean, 25 g/day) to the lowest (mean, 8 g/day) (odds ratio = 0.96; 95% confidence interval, 0.71-1.30).

Finally, the investigators found no associations between dietary fiber intake by subtype (for instance, beans, grains, fruits, and vegetables) and diverticulosis.

"Forty years ago, Dr. Neil Painter popularized the hypothesis that inadequate dietary fiber intake and constipation were the cause of sigmoid diverticulosis," wrote Dr. Peery. However, "Although the fiber hypothesis is conceptually attractive and widely accepted, it has not been rigorously examined."

And while Dr. Peery’s data were based on a food frequency questionnaire – which could be subject to measurement bias – she added that "the mean total fiber intake in the highest quartile was 25 g, versus 8 g in the lowest.

"This wide range makes it unlikely that homogeneity of intake accounts for the null association of fiber with the presence of diverticula," she wrote.

A second study by Dr. Kamyar Shahedi of the University of California Los Angeles/Veteran’s Affairs Center for Outcomes Research and Education, also sought evidence for the commonly held belief that up to 25% of patients with diverticulosis will develop diverticulitis.

Dr. Shahedi and colleagues performed a retrospective survival analysis of 2,222 patients from the Veteran’s Affairs Greater Los Angeles Healthcare System with colonic diverticulosis and a median follow-up of 6.75 years (doi:10.1016/j.cgh.2013.06.020). Patients were excluded if they had any ICD-9 code for diverticulitis or documentation of diverticulitis in the medical record notes at any point before the index date of diverticulosis.

When the researchers looked only at imaging-confirmed or surgical specimen–confirmed cases, just 23 patients (1%) developed acute diverticulitis during the study period, Dr. Shahedi found. This jumped to 95 patients (4.3%) when clinical diagnoses were also used, for an incidence of 6 cases per 1,000 patient years.

Looking at predictors for progression, the authors found that only age was related to the development of diverticulitis, with every year of age at diverticulosis detection conferring a 2.4% lower hazard of developing diverticulitis.

According to the authors, the "widely cited figures" that up to a quarter of patients with diverticulosis will develop acute diverticulitis is based on data collected before the time of routine colon screening. "Therefore, the true denominator of individuals harboring diverticulosis was not accounted for in these calculations," they concluded.

And while their retrospective study does leave room for the possibility that cases were missed, "Future series or patient registries may better standardize the definition of diverticulitis in a prospective cohort," wrote the investigators.

In the meantime, prevalence data such as these "may help to reframe discussions with patients regarding their probability of developing clinically significant diverticulitis."

However, even as these two findings change the way providers counsel patients about the cause and impact of diverticula, a third study, also in December’s issue of Clinical Gastroenterology and Hepatology, adds another wrinkle: Patients who do develop diverticulitis are at increased risk for a diagnosis of irritable bowel syndrome later on.

Dr. Erica Cohen of the VA Greater Los Angeles Healthcare System, and colleagues looked at 1,105 chart-confirmed cases of diverticulitis, identified retrospectively from the same dataset used by Dr. Shahedi (doi:10.1016/j.cgh.2013.03.007).

All cases were matched with controls seen on the same day, the mean follow-up period was 6.3 years, and patients with pre-existing IBS or functional bowel diagnoses were excluded from the study.

The primary outcome was a new IBS diagnosis after the index diverticulitis attack (for cases) or enrollment date (for controls). Ultimately, Dr. Cohen found 24 cases of newly diagnosed IBS during the study period: 20 among diverticulitis cases, and 4 among controls. That translated to a hazard ratio of 4.7 among cases compared with controls, even after adjustment for age, sex, ethnicity, race, inpatient versus outpatient status, and comorbidity score (95% CI, 1.6 –14.0; P = .006).

Dr. Cohen offered several possible explanations for the association between diverticulitis and new diagnosis of IBS.

"Inflammation may alter gastrointestinal reflexes, amplify visceral sensitivity, render the bowel more susceptible to negative effects of microbiota, and alter motility in IBS," she said.

"Another putative mechanism of chronic diverticular disease involves shifts in intestinal microbiota leading to chronic inflammation, similar to theoretical models of IBS," Dr. Cohen said.

"Future research should identify demographic and clinical predictors of post-diverticulitis irritable bowel syndrome and evaluate its incidence in prospective studies to better determine whether the link is causal or merely associative," she concluded.

Finally, a fourth study could help researchers reduce the risk of the painful inflammatory condition: Among diverticulosis patients, higher levels of serum vitamin D were associated significantly with a lower risk of diverticulitis.

In her analysis, also published in the December issue of Clinical Gastroenterology and Hepatology, Dr. Lillias H. Maguire and colleagues identified 9,116 diverticulosis patients and 922 diverticulitis patients from the Partners Healthcare Research Patient Data Registry (doi:10.1016/j.cgh.2013.07.035). All patients had at least one prediagnostic serum vitamin D level on record between 1993 and 2012.

Dr. Maguire of Massachusetts General Hospital, Boston, found that patients with uncomplicated diverticulosis had mean levels of 29.1 ng/mL, versus 25.3 ng/mL among the diverticulitis patients (P less than .0001).

A sensitivity analysis that compared the mean prediagnostic values between cases and controls who had more than one reported vitamin D level yielded similarly significant results: The mean vitamin D level of uncomplicated diverticulosis was 33.0 ng/mL, compared with 28.1 ng/mL for acute diverticulitis patients (P less than .0001), 28.8 ng/mL for complicated diverticulitis patients (P = .002), 23.9 ng/mL for surgical diverticulitis cases (P less than .0001), and 25.5 ng/mL for recurrent diverticulitis patients (P less than .0001).

Indeed, "Compared with patients with acute diverticulitis without other sequelae, patients in the subgroups who developed abscess, required surgery, or had recurrent attacks were observed to have lower prediagnostic levels of vitamin D."

These differences between diverticulitis subgroups did not reach significance except in the cohort of patients who required surgery, who had the lowest levels of all.

"Taken together with prior studies showing an inverse association of 25(OH)D and risk of colonic cancer and inflammatory bowel disease, these results highlight the potential importance of vitamin D in the maintenance of colonic health," the investigators wrote.

"Additional studies in cohorts with more detailed information on potential confounders of this association are warranted," they added.

Dr. Peery, whose study looked at fiber intake among diverticulosis patients, and her collaborators reported having no disclosures, and stated that they received funding from the National Institutes of Health.

Dr. Shahedi, who assessed the incidence of diverticulitis, disclosed that three coinvestigators are employees of Shire Pharmaceuticals, which sponsored their study. Other investigators disclosed ties to Amgen and Ironwood Pharmaceuticals.

Dr. Cohen’s coinvestigators, who studied the prevalence of IBS following diverticulitis, disclosed ties to Ironwood Pharmaceuticals, Prometheus, Takeda Pharmaceuticals, Amgen, Ritter Pharmaceuticals, and Shire. Two investigators were employees of Shire, which funded the research.

Finally, the coinvestigators of Dr. Maguire, who looked at vitamin D levels, reported ties to Shire, Bayer Health, Pfizer, Millennium Pharmaceuticals, and Pozen. They were funded by grants from the American College of Gastroenterology as well as the National Institutes of Health.

Not only is there no link between low-fiber diets and diverticulosis, but the incidence of diverticulitis is not nearly as common as was previously believed.

Those are the conclusions of two new studies in the December issue of Clinical Gastroenterology and Hepatology, both of which challenge long-held beliefs about the causes of these conditions.

In the first study, Dr. Anne F. Peery of the University of North Carolina at Chapel Hill, and her colleagues looked at 539 patients with colonic diverticula and 1,569 controls, all culled from the Vitamin D and Calcium Polyp Prevention Study, a double-blind, placebo-controlled trial of vitamin D and/or calcium for the prevention of colonic adenomas (doi:10.1016/j.cgh.2013.06.033).

Patients with a self-reported history of diverticulosis or diverticulitis were excluded, as were cases with a history of colon resection, inflammatory bowel disease, or familial history of colon cancer. Most cases (88%) had descending or sigmoid colon diverticula, and these patients were significantly older and more likely to be male than were the controls.

According to Dr. Peery and colleagues, there was no difference between cases and controls in terms of mean dietary fiber intake (14.8 g per day versus 15.3 g per day, P = .2) and reported supplemental fiber intake (5% versus 5%, P = .7).

Nor was there any significant link when investigators compared the highest quartile of fiber intake (mean, 25 g/day) to the lowest (mean, 8 g/day) (odds ratio = 0.96; 95% confidence interval, 0.71-1.30).

Finally, the investigators found no associations between dietary fiber intake by subtype (for instance, beans, grains, fruits, and vegetables) and diverticulosis.

"Forty years ago, Dr. Neil Painter popularized the hypothesis that inadequate dietary fiber intake and constipation were the cause of sigmoid diverticulosis," wrote Dr. Peery. However, "Although the fiber hypothesis is conceptually attractive and widely accepted, it has not been rigorously examined."

And while Dr. Peery’s data were based on a food frequency questionnaire – which could be subject to measurement bias – she added that "the mean total fiber intake in the highest quartile was 25 g, versus 8 g in the lowest.

"This wide range makes it unlikely that homogeneity of intake accounts for the null association of fiber with the presence of diverticula," she wrote.

A second study by Dr. Kamyar Shahedi of the University of California Los Angeles/Veteran’s Affairs Center for Outcomes Research and Education, also sought evidence for the commonly held belief that up to 25% of patients with diverticulosis will develop diverticulitis.

Dr. Shahedi and colleagues performed a retrospective survival analysis of 2,222 patients from the Veteran’s Affairs Greater Los Angeles Healthcare System with colonic diverticulosis and a median follow-up of 6.75 years (doi:10.1016/j.cgh.2013.06.020). Patients were excluded if they had any ICD-9 code for diverticulitis or documentation of diverticulitis in the medical record notes at any point before the index date of diverticulosis.

When the researchers looked only at imaging-confirmed or surgical specimen–confirmed cases, just 23 patients (1%) developed acute diverticulitis during the study period, Dr. Shahedi found. This jumped to 95 patients (4.3%) when clinical diagnoses were also used, for an incidence of 6 cases per 1,000 patient years.

Looking at predictors for progression, the authors found that only age was related to the development of diverticulitis, with every year of age at diverticulosis detection conferring a 2.4% lower hazard of developing diverticulitis.

According to the authors, the "widely cited figures" that up to a quarter of patients with diverticulosis will develop acute diverticulitis is based on data collected before the time of routine colon screening. "Therefore, the true denominator of individuals harboring diverticulosis was not accounted for in these calculations," they concluded.

And while their retrospective study does leave room for the possibility that cases were missed, "Future series or patient registries may better standardize the definition of diverticulitis in a prospective cohort," wrote the investigators.

In the meantime, prevalence data such as these "may help to reframe discussions with patients regarding their probability of developing clinically significant diverticulitis."

However, even as these two findings change the way providers counsel patients about the cause and impact of diverticula, a third study, also in December’s issue of Clinical Gastroenterology and Hepatology, adds another wrinkle: Patients who do develop diverticulitis are at increased risk for a diagnosis of irritable bowel syndrome later on.

Dr. Erica Cohen of the VA Greater Los Angeles Healthcare System, and colleagues looked at 1,105 chart-confirmed cases of diverticulitis, identified retrospectively from the same dataset used by Dr. Shahedi (doi:10.1016/j.cgh.2013.03.007).

All cases were matched with controls seen on the same day, the mean follow-up period was 6.3 years, and patients with pre-existing IBS or functional bowel diagnoses were excluded from the study.

The primary outcome was a new IBS diagnosis after the index diverticulitis attack (for cases) or enrollment date (for controls). Ultimately, Dr. Cohen found 24 cases of newly diagnosed IBS during the study period: 20 among diverticulitis cases, and 4 among controls. That translated to a hazard ratio of 4.7 among cases compared with controls, even after adjustment for age, sex, ethnicity, race, inpatient versus outpatient status, and comorbidity score (95% CI, 1.6 –14.0; P = .006).

Dr. Cohen offered several possible explanations for the association between diverticulitis and new diagnosis of IBS.

"Inflammation may alter gastrointestinal reflexes, amplify visceral sensitivity, render the bowel more susceptible to negative effects of microbiota, and alter motility in IBS," she said.

"Another putative mechanism of chronic diverticular disease involves shifts in intestinal microbiota leading to chronic inflammation, similar to theoretical models of IBS," Dr. Cohen said.

"Future research should identify demographic and clinical predictors of post-diverticulitis irritable bowel syndrome and evaluate its incidence in prospective studies to better determine whether the link is causal or merely associative," she concluded.

Finally, a fourth study could help researchers reduce the risk of the painful inflammatory condition: Among diverticulosis patients, higher levels of serum vitamin D were associated significantly with a lower risk of diverticulitis.

In her analysis, also published in the December issue of Clinical Gastroenterology and Hepatology, Dr. Lillias H. Maguire and colleagues identified 9,116 diverticulosis patients and 922 diverticulitis patients from the Partners Healthcare Research Patient Data Registry (doi:10.1016/j.cgh.2013.07.035). All patients had at least one prediagnostic serum vitamin D level on record between 1993 and 2012.

Dr. Maguire of Massachusetts General Hospital, Boston, found that patients with uncomplicated diverticulosis had mean levels of 29.1 ng/mL, versus 25.3 ng/mL among the diverticulitis patients (P less than .0001).

A sensitivity analysis that compared the mean prediagnostic values between cases and controls who had more than one reported vitamin D level yielded similarly significant results: The mean vitamin D level of uncomplicated diverticulosis was 33.0 ng/mL, compared with 28.1 ng/mL for acute diverticulitis patients (P less than .0001), 28.8 ng/mL for complicated diverticulitis patients (P = .002), 23.9 ng/mL for surgical diverticulitis cases (P less than .0001), and 25.5 ng/mL for recurrent diverticulitis patients (P less than .0001).

Indeed, "Compared with patients with acute diverticulitis without other sequelae, patients in the subgroups who developed abscess, required surgery, or had recurrent attacks were observed to have lower prediagnostic levels of vitamin D."

These differences between diverticulitis subgroups did not reach significance except in the cohort of patients who required surgery, who had the lowest levels of all.

"Taken together with prior studies showing an inverse association of 25(OH)D and risk of colonic cancer and inflammatory bowel disease, these results highlight the potential importance of vitamin D in the maintenance of colonic health," the investigators wrote.

"Additional studies in cohorts with more detailed information on potential confounders of this association are warranted," they added.

Dr. Peery, whose study looked at fiber intake among diverticulosis patients, and her collaborators reported having no disclosures, and stated that they received funding from the National Institutes of Health.

Dr. Shahedi, who assessed the incidence of diverticulitis, disclosed that three coinvestigators are employees of Shire Pharmaceuticals, which sponsored their study. Other investigators disclosed ties to Amgen and Ironwood Pharmaceuticals.

Dr. Cohen’s coinvestigators, who studied the prevalence of IBS following diverticulitis, disclosed ties to Ironwood Pharmaceuticals, Prometheus, Takeda Pharmaceuticals, Amgen, Ritter Pharmaceuticals, and Shire. Two investigators were employees of Shire, which funded the research.

Finally, the coinvestigators of Dr. Maguire, who looked at vitamin D levels, reported ties to Shire, Bayer Health, Pfizer, Millennium Pharmaceuticals, and Pozen. They were funded by grants from the American College of Gastroenterology as well as the National Institutes of Health.

The longer the interval between symptom onset and the diagnosis of eosinophilic esophagitis, the greater the chance that the patient will have developed esophageal strictures, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.015).

In a retrospective study of 523 cases of eosinophilic esophagitis (EoE) recorded in a national Swiss database, patients "were likely to present with purely inflammatory endoscopic EoE features early in the disease course and then progress to develop fibrotic endoscopic features, in addition to inflammatory features," said Dr. Alain M. Schoepfer of the division of gastroenerology and hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and his associates.

Moreover, an additional analysis of numerous potential disease-, environmental-, and patient-related risk factors demonstrated that the length of diagnostic delay is the single strongest risk factor for stricture formation, the investigators noted.

The natural history of untreated EoE has not been investigated extensively, and data regarding stricture formation are particularly lacking. In addition, eosinophilic esophagitis has long been associated with a substantial delay in diagnosis, with a median of 5 years elapsing between symptom onset and correct identification of the disorder.

Dr. Schoepfer and his colleagues examined the relationship between the duration of untreated disease (before EoE was diagnosed) and the prevalence of esophageal stricture using a database with detailed medical records of 323 patients they personally diagnosed and treated plus 200 others who were diagnosed and treated by other gastroenterologists throughout Switzerland. The database included the results from numerous biopsies of the proximal and distal esophagus for every patient, as well as information on 98 clinical factors that might influence stricture formation.

The median diagnostic delay was 6 years (range, 0 to more than 20 years).

Strictures were present at diagnosis in 75 patients (37.5%).

Features of active inflammation, such as edema, furrows, and whitish exudates, were present in 79.5% of patients while features of fibrotic activity, such as strictures, rings, and crepe-paper esophagus, were seen in 63.0%.

The prevalence of fibrotic features including strictures increased with increasing duration of diagnostic delay. This prevalence was 46.5% among patients who were diagnosed as having EoE within 0-2 years of symptom onset, rising to 87.5% among those diagnosed 20 years or more after symptom onset.

In contrast, the prevalence of inflammatory features alone decreased with increasing duration of diagnostic delay.

The prevalence of esophageal strictures likewise correlated with diagnostic delay. It was 17.2% among patients diagnosed within 0-2 years of symptom onset, compared with 70.8% among those diagnosed 20 years or more after symptom onset, the investigators said.

The prevalence of strictures did not differ by patient age at diagnosis. It was comparable between patients who were diagnosed before they reached 20 years of age and those diagnosed after age 20. The prevalence of strictures also did not differ between the 323 patients diagnosed and treated by Dr. Schoepfer and his associates, who were managed according to a strict standardized protocol, and the 200 other patients who were managed by numerous other gastroenterologists according to their own individual practice preferences.

In an analysis of nearly 100 potential risk factors for stricture formation, only the length of diagnostic delay was found to be significantly associated with the presence of strictures at diagnosis.

These findings demonstrate that a patient’s disease course "is a continuum – a march from a disease predominantly inflammatory in nature to a disease with endoscopic fibrotic features, including strictures, in addition to existing inflammation," the researchers said.

Clinicians should make every effort to reduce the delay in diagnosis of EoE, they added.

This study was supported by the Swiss National Science Foundation. No relevant financial conflicts of interest were reported.

The longer the interval between symptom onset and the diagnosis of eosinophilic esophagitis, the greater the chance that the patient will have developed esophageal strictures, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.015).

In a retrospective study of 523 cases of eosinophilic esophagitis (EoE) recorded in a national Swiss database, patients "were likely to present with purely inflammatory endoscopic EoE features early in the disease course and then progress to develop fibrotic endoscopic features, in addition to inflammatory features," said Dr. Alain M. Schoepfer of the division of gastroenerology and hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and his associates.

Moreover, an additional analysis of numerous potential disease-, environmental-, and patient-related risk factors demonstrated that the length of diagnostic delay is the single strongest risk factor for stricture formation, the investigators noted.

The natural history of untreated EoE has not been investigated extensively, and data regarding stricture formation are particularly lacking. In addition, eosinophilic esophagitis has long been associated with a substantial delay in diagnosis, with a median of 5 years elapsing between symptom onset and correct identification of the disorder.

Dr. Schoepfer and his colleagues examined the relationship between the duration of untreated disease (before EoE was diagnosed) and the prevalence of esophageal stricture using a database with detailed medical records of 323 patients they personally diagnosed and treated plus 200 others who were diagnosed and treated by other gastroenterologists throughout Switzerland. The database included the results from numerous biopsies of the proximal and distal esophagus for every patient, as well as information on 98 clinical factors that might influence stricture formation.

The median diagnostic delay was 6 years (range, 0 to more than 20 years).

Strictures were present at diagnosis in 75 patients (37.5%).

Features of active inflammation, such as edema, furrows, and whitish exudates, were present in 79.5% of patients while features of fibrotic activity, such as strictures, rings, and crepe-paper esophagus, were seen in 63.0%.

The prevalence of fibrotic features including strictures increased with increasing duration of diagnostic delay. This prevalence was 46.5% among patients who were diagnosed as having EoE within 0-2 years of symptom onset, rising to 87.5% among those diagnosed 20 years or more after symptom onset.

In contrast, the prevalence of inflammatory features alone decreased with increasing duration of diagnostic delay.

The prevalence of esophageal strictures likewise correlated with diagnostic delay. It was 17.2% among patients diagnosed within 0-2 years of symptom onset, compared with 70.8% among those diagnosed 20 years or more after symptom onset, the investigators said.

The prevalence of strictures did not differ by patient age at diagnosis. It was comparable between patients who were diagnosed before they reached 20 years of age and those diagnosed after age 20. The prevalence of strictures also did not differ between the 323 patients diagnosed and treated by Dr. Schoepfer and his associates, who were managed according to a strict standardized protocol, and the 200 other patients who were managed by numerous other gastroenterologists according to their own individual practice preferences.

In an analysis of nearly 100 potential risk factors for stricture formation, only the length of diagnostic delay was found to be significantly associated with the presence of strictures at diagnosis.

These findings demonstrate that a patient’s disease course "is a continuum – a march from a disease predominantly inflammatory in nature to a disease with endoscopic fibrotic features, including strictures, in addition to existing inflammation," the researchers said.

Clinicians should make every effort to reduce the delay in diagnosis of EoE, they added.

This study was supported by the Swiss National Science Foundation. No relevant financial conflicts of interest were reported.

The longer the interval between symptom onset and the diagnosis of eosinophilic esophagitis, the greater the chance that the patient will have developed esophageal strictures, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.015).

In a retrospective study of 523 cases of eosinophilic esophagitis (EoE) recorded in a national Swiss database, patients "were likely to present with purely inflammatory endoscopic EoE features early in the disease course and then progress to develop fibrotic endoscopic features, in addition to inflammatory features," said Dr. Alain M. Schoepfer of the division of gastroenerology and hepatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and his associates.

Moreover, an additional analysis of numerous potential disease-, environmental-, and patient-related risk factors demonstrated that the length of diagnostic delay is the single strongest risk factor for stricture formation, the investigators noted.

The natural history of untreated EoE has not been investigated extensively, and data regarding stricture formation are particularly lacking. In addition, eosinophilic esophagitis has long been associated with a substantial delay in diagnosis, with a median of 5 years elapsing between symptom onset and correct identification of the disorder.

Dr. Schoepfer and his colleagues examined the relationship between the duration of untreated disease (before EoE was diagnosed) and the prevalence of esophageal stricture using a database with detailed medical records of 323 patients they personally diagnosed and treated plus 200 others who were diagnosed and treated by other gastroenterologists throughout Switzerland. The database included the results from numerous biopsies of the proximal and distal esophagus for every patient, as well as information on 98 clinical factors that might influence stricture formation.

The median diagnostic delay was 6 years (range, 0 to more than 20 years).

Strictures were present at diagnosis in 75 patients (37.5%).

Features of active inflammation, such as edema, furrows, and whitish exudates, were present in 79.5% of patients while features of fibrotic activity, such as strictures, rings, and crepe-paper esophagus, were seen in 63.0%.

The prevalence of fibrotic features including strictures increased with increasing duration of diagnostic delay. This prevalence was 46.5% among patients who were diagnosed as having EoE within 0-2 years of symptom onset, rising to 87.5% among those diagnosed 20 years or more after symptom onset.

In contrast, the prevalence of inflammatory features alone decreased with increasing duration of diagnostic delay.

The prevalence of esophageal strictures likewise correlated with diagnostic delay. It was 17.2% among patients diagnosed within 0-2 years of symptom onset, compared with 70.8% among those diagnosed 20 years or more after symptom onset, the investigators said.

The prevalence of strictures did not differ by patient age at diagnosis. It was comparable between patients who were diagnosed before they reached 20 years of age and those diagnosed after age 20. The prevalence of strictures also did not differ between the 323 patients diagnosed and treated by Dr. Schoepfer and his associates, who were managed according to a strict standardized protocol, and the 200 other patients who were managed by numerous other gastroenterologists according to their own individual practice preferences.

In an analysis of nearly 100 potential risk factors for stricture formation, only the length of diagnostic delay was found to be significantly associated with the presence of strictures at diagnosis.

These findings demonstrate that a patient’s disease course "is a continuum – a march from a disease predominantly inflammatory in nature to a disease with endoscopic fibrotic features, including strictures, in addition to existing inflammation," the researchers said.

Clinicians should make every effort to reduce the delay in diagnosis of EoE, they added.

This study was supported by the Swiss National Science Foundation. No relevant financial conflicts of interest were reported.

The newly proposed consensus definition of acute kidney injury in patients with cirrhosis accurately predicts 30-day mortality and other adverse outcomes in this patient population much better than the current, more rigid definition would, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.051).

In what they described as the largest prospective study of this topic to date, researchers found that the recently proposed, broader redefinition of acute kidney injury (AKI) correctly identified which patients were likely to die, develop severe complications such as organ failure, or require longer hospitalization, even when the AKI was transient and resolved completely after treatment.

Courtesy American Gastroenterological Association

More than half of the patients in this study who had episodes of AKI according to the new definition did not meet the criteria of the old definition. So using the new definition will help identify these high-risk patients at an earlier stage of renal dysfunction, "well before the stringent diagnostic criteria of [the old definition] are reached," when they will have a better treatment response, said Dr. Florence Wong of the division of gastroenterology, University of Toronto, and her associates.

The old definition of AKI required the presence of hepatorenal syndrome, with a serum creatinine level of greater than 2.5 mg/dL. This meant that patients with less severe renal dysfunction didn’t qualify and weren’t treated. But emerging evidence indicates that even mild degrees of renal dysfunction signal a poor prognosis, and that serum creatinine alone doesn’t accurately reflect renal dysfunction in advanced cirrhosis.

So the International Ascites Club and the Acute Dialysis Quality Initiative (ADQI) group proposed that acute kidney injury in cirrhosis should be redefined as an increase in serum creatinine level of 0.3 mg/dL or greater within 48 hours, or a 50% increase in serum creatinine level from a stable baseline reading within the previous 6 months, regardless of final serum creatinine level.

Dr. Wong and her colleagues assessed the new definition in a cohort of 337 cirrhotic patients treated during a 2-year period at 12 North American medical centers who were admitted with a bacterial infection (287 subjects) or who developed a bacterial infection during hospitalization (50 subjects). The most common infections were urinary tract infection (27% of patients), spontaneous bacterial peritonitis (21%), skin infection (14%), pneumonia (10%), and spontaneous bacteremia with no clear source of infection (9%).

Approximately half of these patients (49%) developed at least one episode of AKI during hospitalization. The 30-day mortality was significantly higher for those who developed AKI according to the new definition (34% mortality) than in those who did not (7% mortality), the investigators said.

Most patients who developed AKI had only a transient case, and their renal function completely recovered. Yet their subsequent mortality within 30 days was twice as high as that for patients who didn’t have any AKI.

The negative predictive value of the new definition of AKI was 93%, and the positive predictive value was 34%.

This study was supported in part by the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources. No financial conflicts of interest were reported.

The newly proposed consensus definition of acute kidney injury in patients with cirrhosis accurately predicts 30-day mortality and other adverse outcomes in this patient population much better than the current, more rigid definition would, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.051).

In what they described as the largest prospective study of this topic to date, researchers found that the recently proposed, broader redefinition of acute kidney injury (AKI) correctly identified which patients were likely to die, develop severe complications such as organ failure, or require longer hospitalization, even when the AKI was transient and resolved completely after treatment.

Courtesy American Gastroenterological Association

More than half of the patients in this study who had episodes of AKI according to the new definition did not meet the criteria of the old definition. So using the new definition will help identify these high-risk patients at an earlier stage of renal dysfunction, "well before the stringent diagnostic criteria of [the old definition] are reached," when they will have a better treatment response, said Dr. Florence Wong of the division of gastroenterology, University of Toronto, and her associates.

The old definition of AKI required the presence of hepatorenal syndrome, with a serum creatinine level of greater than 2.5 mg/dL. This meant that patients with less severe renal dysfunction didn’t qualify and weren’t treated. But emerging evidence indicates that even mild degrees of renal dysfunction signal a poor prognosis, and that serum creatinine alone doesn’t accurately reflect renal dysfunction in advanced cirrhosis.

So the International Ascites Club and the Acute Dialysis Quality Initiative (ADQI) group proposed that acute kidney injury in cirrhosis should be redefined as an increase in serum creatinine level of 0.3 mg/dL or greater within 48 hours, or a 50% increase in serum creatinine level from a stable baseline reading within the previous 6 months, regardless of final serum creatinine level.

Dr. Wong and her colleagues assessed the new definition in a cohort of 337 cirrhotic patients treated during a 2-year period at 12 North American medical centers who were admitted with a bacterial infection (287 subjects) or who developed a bacterial infection during hospitalization (50 subjects). The most common infections were urinary tract infection (27% of patients), spontaneous bacterial peritonitis (21%), skin infection (14%), pneumonia (10%), and spontaneous bacteremia with no clear source of infection (9%).

Approximately half of these patients (49%) developed at least one episode of AKI during hospitalization. The 30-day mortality was significantly higher for those who developed AKI according to the new definition (34% mortality) than in those who did not (7% mortality), the investigators said.

Most patients who developed AKI had only a transient case, and their renal function completely recovered. Yet their subsequent mortality within 30 days was twice as high as that for patients who didn’t have any AKI.

The negative predictive value of the new definition of AKI was 93%, and the positive predictive value was 34%.

This study was supported in part by the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources. No financial conflicts of interest were reported.

The newly proposed consensus definition of acute kidney injury in patients with cirrhosis accurately predicts 30-day mortality and other adverse outcomes in this patient population much better than the current, more rigid definition would, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.051).

In what they described as the largest prospective study of this topic to date, researchers found that the recently proposed, broader redefinition of acute kidney injury (AKI) correctly identified which patients were likely to die, develop severe complications such as organ failure, or require longer hospitalization, even when the AKI was transient and resolved completely after treatment.

Courtesy American Gastroenterological Association

More than half of the patients in this study who had episodes of AKI according to the new definition did not meet the criteria of the old definition. So using the new definition will help identify these high-risk patients at an earlier stage of renal dysfunction, "well before the stringent diagnostic criteria of [the old definition] are reached," when they will have a better treatment response, said Dr. Florence Wong of the division of gastroenterology, University of Toronto, and her associates.

The old definition of AKI required the presence of hepatorenal syndrome, with a serum creatinine level of greater than 2.5 mg/dL. This meant that patients with less severe renal dysfunction didn’t qualify and weren’t treated. But emerging evidence indicates that even mild degrees of renal dysfunction signal a poor prognosis, and that serum creatinine alone doesn’t accurately reflect renal dysfunction in advanced cirrhosis.

So the International Ascites Club and the Acute Dialysis Quality Initiative (ADQI) group proposed that acute kidney injury in cirrhosis should be redefined as an increase in serum creatinine level of 0.3 mg/dL or greater within 48 hours, or a 50% increase in serum creatinine level from a stable baseline reading within the previous 6 months, regardless of final serum creatinine level.

Dr. Wong and her colleagues assessed the new definition in a cohort of 337 cirrhotic patients treated during a 2-year period at 12 North American medical centers who were admitted with a bacterial infection (287 subjects) or who developed a bacterial infection during hospitalization (50 subjects). The most common infections were urinary tract infection (27% of patients), spontaneous bacterial peritonitis (21%), skin infection (14%), pneumonia (10%), and spontaneous bacteremia with no clear source of infection (9%).

Approximately half of these patients (49%) developed at least one episode of AKI during hospitalization. The 30-day mortality was significantly higher for those who developed AKI according to the new definition (34% mortality) than in those who did not (7% mortality), the investigators said.

Most patients who developed AKI had only a transient case, and their renal function completely recovered. Yet their subsequent mortality within 30 days was twice as high as that for patients who didn’t have any AKI.

The negative predictive value of the new definition of AKI was 93%, and the positive predictive value was 34%.

This study was supported in part by the National Institutes of Health, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources. No financial conflicts of interest were reported.

A reduction of at least 50% in either of two different Crohn’s disease endoscopic activity scores after 26 weeks of treatment predicted those patients likely to be off of corticosteroid therapy after about 1 year of treatment, with a sensitivity approaching 75%, reported Dr. Marc Ferrante and his coinvestigators.

The study provides evidence that this cutoff could be used as a reliable predictor of clinical response, but it needs to be studied further, according to the authors, who are members of the International Organization for the Study of Inflammatory Bowel Diseases. The study was published in the Novemberissue of Gastroenterology.

Another study, published in the same issue of Gastroenterology, evaluated the reliability of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), an instrument recently created to assess the endoscopic severity of UC. This study randomized 25 investigators to assess and score 28 endoscopic videos of patients with UC – without knowledge of clinical features in most cases. The results indicated that the UCEIS provides a "satisfactory" level of intrainvestigator and interinvestigator agreement and that it is "a reliable instrument for measuring the endoscopic disease activity of UC," according to Dr. Simon Travis, of the translational gastroenterology unit at John Radcliffe Hospital, Oxford, England, and his coinvestigators.

The version of the UCEIS that provides a score from 0 to 8, based on findings of vascular pattern, bleeding, and erosions/ulcers, is the "favored version" but needs to be validated further, they concluded (Gastroenterol. 2013 July 29 [doi: 10.1053/j.gastro.2013.07.024]).

In the Crohn’s disease (CD) study, which used data on 172 patients enrolled in SONIC (Study of Biologic and Immunomodulator Naive Patients in Crohn’s Disease), Dr. Ferrante, of the department of gastroenterology at University Hospitals Leuven, Belgium, and his colleagues identified a cutoff point in two endoscopic response scores after 26 weeks of treatment that was predictive of clinical response at 50 weeks.

At baseline, the patients had endoscopic lesions and CD Activity Index (CDAI) scores of 220-450 points (median, 277). Their median age was 34 years, and they had been diagnosed with CD for a median of 2.5 years. The patients were dependent on corticosteroids and were randomized to treatment with infliximab (Remicade) infusions and/or oral azathioprine, and were followed to 50 weeks. The primary endpoint of this study was corticosteroid-free clinical remission (CFREM) at week 26, and one of the secondary endpoints was complete healing of mucosal ulcerations.

The investigators evaluated different cutoff points of endoscopic responses for two methods used to score the severity of endoscopic lesions: SES-CD (Simple Endoscopic Score for CD) and CDEIS (CD Endoscopic Index of Severity).

Almost half of the patients achieved mucosal healing at the 26th week.

A decrease from baseline in the SES-CD of at least 50% at week 26 "appeared to be the best discriminative cutoff value" for predicting patients most likely to be in clinical remission (off steroids at week 50). This degree of SES-CD response was met by 112 (65%) patients, with 74% sensitivity and 48% specificity for predicting CFREM at week 50.

For the CDEIS values, the best cutoff was at least a 45% drop from baseline at week 26 for predicting patients most likely to achieve CFREM at week 50, with 75% sensitivity and 45% specificity.

Because of the "subtle" difference between the two measures (50% and 45% cutoffs), "we propose a definition of endoscopic response with a decrease in baseline in CDEIS of at least 50% at week 26 for both tests," the authors wrote. (For CDEIS, the 50% cutoff had a sensitivity of 73% and a specificity of 46%.)

"As such, this endoscopic endpoint could serve as a reliable predictor of the midterm clinical outcome of therapies," Dr. Ferrante and his coauthors concluded. A 50% reduction in endoscopic activity from baseline also has potential for use as an endpoint in studies evaluating pharmacotherapy or treatment strategies "to show healing capacity," they wrote.

These cutoff values should be validated in a prospective study, which should also look at correlations between the endoscopic response and "disease-modifying long-term outcomes," such as a sustained clinical response or surgery, they added.

In the study that evaluated the reliability of the UCEIS, 25 investigators from North America and Europe were randomized to assess 28 of 57 sigmoidoscopy videos of patients with UC, which included some duplicates to evaluate intraobserver reliability. Clinical details such as the number of stools per day were provided for only two of the videos. They were also trained.

The UCEIS provides a score of 0 to 8 based on the sum of three descriptors: vascular pattern (normal, patchy obliteration, or obliterated), bleeding (none, mucosal, luminal mild, luminal moderate, or severe), and erosions and ulcers (none, erosions, superficial ulcer, or deep ulcer). Almost 700 video evaluations were performed.

The results included a satisfactory level of intrainvestigator and interinvestigator reliability, indicating that the UCEIS is simple to use and also "reliably evaluates the overall endoscopic severity of UC and accounts for 88% of the variance between endoscopists," the authors concluded.

The study was the first step in the validation of the UCEIS and has "confirmed the reliability of the UCEIS, even if further validation is needed to establish thresholds for remission, the clinical relevance of different UCEIS scores, and responsiveness of the UCEIS to change in disease status," they noted.

The CD study was partly funded by Janssen Biotech; Dr. Ferrante was supported by the Belgian Society of Gastrointestinal Endoscopy and by Funds for Scientific Research, Belgium. The authors disclosed serving on advisory committees and review panels of, or serving as consultants and speakers for, multiple pharmaceutical manufacturers, as well as receiving grants or research support from the companies, including Janssen and Abbott. Several authors were employees of Janssen Biotech and Janssen Biologics, the manufacturer of infliximab. One author had no disclosures.

The UCEIS study was funded by Warner Chilcott, and one author was an employee of the company. The authors disclosed serving as consultants, advisers, and/or speakers for, and receiving research grants from, multiple pharmaceutical companies. Several authors had no disclosures.

[email protected]

A reduction of at least 50% in either of two different Crohn’s disease endoscopic activity scores after 26 weeks of treatment predicted those patients likely to be off of corticosteroid therapy after about 1 year of treatment, with a sensitivity approaching 75%, reported Dr. Marc Ferrante and his coinvestigators.

The study provides evidence that this cutoff could be used as a reliable predictor of clinical response, but it needs to be studied further, according to the authors, who are members of the International Organization for the Study of Inflammatory Bowel Diseases. The study was published in the Novemberissue of Gastroenterology.

Another study, published in the same issue of Gastroenterology, evaluated the reliability of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), an instrument recently created to assess the endoscopic severity of UC. This study randomized 25 investigators to assess and score 28 endoscopic videos of patients with UC – without knowledge of clinical features in most cases. The results indicated that the UCEIS provides a "satisfactory" level of intrainvestigator and interinvestigator agreement and that it is "a reliable instrument for measuring the endoscopic disease activity of UC," according to Dr. Simon Travis, of the translational gastroenterology unit at John Radcliffe Hospital, Oxford, England, and his coinvestigators.

The version of the UCEIS that provides a score from 0 to 8, based on findings of vascular pattern, bleeding, and erosions/ulcers, is the "favored version" but needs to be validated further, they concluded (Gastroenterol. 2013 July 29 [doi: 10.1053/j.gastro.2013.07.024]).

In the Crohn’s disease (CD) study, which used data on 172 patients enrolled in SONIC (Study of Biologic and Immunomodulator Naive Patients in Crohn’s Disease), Dr. Ferrante, of the department of gastroenterology at University Hospitals Leuven, Belgium, and his colleagues identified a cutoff point in two endoscopic response scores after 26 weeks of treatment that was predictive of clinical response at 50 weeks.

At baseline, the patients had endoscopic lesions and CD Activity Index (CDAI) scores of 220-450 points (median, 277). Their median age was 34 years, and they had been diagnosed with CD for a median of 2.5 years. The patients were dependent on corticosteroids and were randomized to treatment with infliximab (Remicade) infusions and/or oral azathioprine, and were followed to 50 weeks. The primary endpoint of this study was corticosteroid-free clinical remission (CFREM) at week 26, and one of the secondary endpoints was complete healing of mucosal ulcerations.

The investigators evaluated different cutoff points of endoscopic responses for two methods used to score the severity of endoscopic lesions: SES-CD (Simple Endoscopic Score for CD) and CDEIS (CD Endoscopic Index of Severity).

Almost half of the patients achieved mucosal healing at the 26th week.

A decrease from baseline in the SES-CD of at least 50% at week 26 "appeared to be the best discriminative cutoff value" for predicting patients most likely to be in clinical remission (off steroids at week 50). This degree of SES-CD response was met by 112 (65%) patients, with 74% sensitivity and 48% specificity for predicting CFREM at week 50.

For the CDEIS values, the best cutoff was at least a 45% drop from baseline at week 26 for predicting patients most likely to achieve CFREM at week 50, with 75% sensitivity and 45% specificity.

Because of the "subtle" difference between the two measures (50% and 45% cutoffs), "we propose a definition of endoscopic response with a decrease in baseline in CDEIS of at least 50% at week 26 for both tests," the authors wrote. (For CDEIS, the 50% cutoff had a sensitivity of 73% and a specificity of 46%.)

"As such, this endoscopic endpoint could serve as a reliable predictor of the midterm clinical outcome of therapies," Dr. Ferrante and his coauthors concluded. A 50% reduction in endoscopic activity from baseline also has potential for use as an endpoint in studies evaluating pharmacotherapy or treatment strategies "to show healing capacity," they wrote.

These cutoff values should be validated in a prospective study, which should also look at correlations between the endoscopic response and "disease-modifying long-term outcomes," such as a sustained clinical response or surgery, they added.

In the study that evaluated the reliability of the UCEIS, 25 investigators from North America and Europe were randomized to assess 28 of 57 sigmoidoscopy videos of patients with UC, which included some duplicates to evaluate intraobserver reliability. Clinical details such as the number of stools per day were provided for only two of the videos. They were also trained.

The UCEIS provides a score of 0 to 8 based on the sum of three descriptors: vascular pattern (normal, patchy obliteration, or obliterated), bleeding (none, mucosal, luminal mild, luminal moderate, or severe), and erosions and ulcers (none, erosions, superficial ulcer, or deep ulcer). Almost 700 video evaluations were performed.

The results included a satisfactory level of intrainvestigator and interinvestigator reliability, indicating that the UCEIS is simple to use and also "reliably evaluates the overall endoscopic severity of UC and accounts for 88% of the variance between endoscopists," the authors concluded.

The study was the first step in the validation of the UCEIS and has "confirmed the reliability of the UCEIS, even if further validation is needed to establish thresholds for remission, the clinical relevance of different UCEIS scores, and responsiveness of the UCEIS to change in disease status," they noted.

The CD study was partly funded by Janssen Biotech; Dr. Ferrante was supported by the Belgian Society of Gastrointestinal Endoscopy and by Funds for Scientific Research, Belgium. The authors disclosed serving on advisory committees and review panels of, or serving as consultants and speakers for, multiple pharmaceutical manufacturers, as well as receiving grants or research support from the companies, including Janssen and Abbott. Several authors were employees of Janssen Biotech and Janssen Biologics, the manufacturer of infliximab. One author had no disclosures.

The UCEIS study was funded by Warner Chilcott, and one author was an employee of the company. The authors disclosed serving as consultants, advisers, and/or speakers for, and receiving research grants from, multiple pharmaceutical companies. Several authors had no disclosures.

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A reduction of at least 50% in either of two different Crohn’s disease endoscopic activity scores after 26 weeks of treatment predicted those patients likely to be off of corticosteroid therapy after about 1 year of treatment, with a sensitivity approaching 75%, reported Dr. Marc Ferrante and his coinvestigators.

The study provides evidence that this cutoff could be used as a reliable predictor of clinical response, but it needs to be studied further, according to the authors, who are members of the International Organization for the Study of Inflammatory Bowel Diseases. The study was published in the Novemberissue of Gastroenterology.

Another study, published in the same issue of Gastroenterology, evaluated the reliability of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), an instrument recently created to assess the endoscopic severity of UC. This study randomized 25 investigators to assess and score 28 endoscopic videos of patients with UC – without knowledge of clinical features in most cases. The results indicated that the UCEIS provides a "satisfactory" level of intrainvestigator and interinvestigator agreement and that it is "a reliable instrument for measuring the endoscopic disease activity of UC," according to Dr. Simon Travis, of the translational gastroenterology unit at John Radcliffe Hospital, Oxford, England, and his coinvestigators.

The version of the UCEIS that provides a score from 0 to 8, based on findings of vascular pattern, bleeding, and erosions/ulcers, is the "favored version" but needs to be validated further, they concluded (Gastroenterol. 2013 July 29 [doi: 10.1053/j.gastro.2013.07.024]).

In the Crohn’s disease (CD) study, which used data on 172 patients enrolled in SONIC (Study of Biologic and Immunomodulator Naive Patients in Crohn’s Disease), Dr. Ferrante, of the department of gastroenterology at University Hospitals Leuven, Belgium, and his colleagues identified a cutoff point in two endoscopic response scores after 26 weeks of treatment that was predictive of clinical response at 50 weeks.

At baseline, the patients had endoscopic lesions and CD Activity Index (CDAI) scores of 220-450 points (median, 277). Their median age was 34 years, and they had been diagnosed with CD for a median of 2.5 years. The patients were dependent on corticosteroids and were randomized to treatment with infliximab (Remicade) infusions and/or oral azathioprine, and were followed to 50 weeks. The primary endpoint of this study was corticosteroid-free clinical remission (CFREM) at week 26, and one of the secondary endpoints was complete healing of mucosal ulcerations.

The investigators evaluated different cutoff points of endoscopic responses for two methods used to score the severity of endoscopic lesions: SES-CD (Simple Endoscopic Score for CD) and CDEIS (CD Endoscopic Index of Severity).

Almost half of the patients achieved mucosal healing at the 26th week.

A decrease from baseline in the SES-CD of at least 50% at week 26 "appeared to be the best discriminative cutoff value" for predicting patients most likely to be in clinical remission (off steroids at week 50). This degree of SES-CD response was met by 112 (65%) patients, with 74% sensitivity and 48% specificity for predicting CFREM at week 50.

For the CDEIS values, the best cutoff was at least a 45% drop from baseline at week 26 for predicting patients most likely to achieve CFREM at week 50, with 75% sensitivity and 45% specificity.

Because of the "subtle" difference between the two measures (50% and 45% cutoffs), "we propose a definition of endoscopic response with a decrease in baseline in CDEIS of at least 50% at week 26 for both tests," the authors wrote. (For CDEIS, the 50% cutoff had a sensitivity of 73% and a specificity of 46%.)

"As such, this endoscopic endpoint could serve as a reliable predictor of the midterm clinical outcome of therapies," Dr. Ferrante and his coauthors concluded. A 50% reduction in endoscopic activity from baseline also has potential for use as an endpoint in studies evaluating pharmacotherapy or treatment strategies "to show healing capacity," they wrote.

These cutoff values should be validated in a prospective study, which should also look at correlations between the endoscopic response and "disease-modifying long-term outcomes," such as a sustained clinical response or surgery, they added.

In the study that evaluated the reliability of the UCEIS, 25 investigators from North America and Europe were randomized to assess 28 of 57 sigmoidoscopy videos of patients with UC, which included some duplicates to evaluate intraobserver reliability. Clinical details such as the number of stools per day were provided for only two of the videos. They were also trained.

The UCEIS provides a score of 0 to 8 based on the sum of three descriptors: vascular pattern (normal, patchy obliteration, or obliterated), bleeding (none, mucosal, luminal mild, luminal moderate, or severe), and erosions and ulcers (none, erosions, superficial ulcer, or deep ulcer). Almost 700 video evaluations were performed.

The results included a satisfactory level of intrainvestigator and interinvestigator reliability, indicating that the UCEIS is simple to use and also "reliably evaluates the overall endoscopic severity of UC and accounts for 88% of the variance between endoscopists," the authors concluded.

The study was the first step in the validation of the UCEIS and has "confirmed the reliability of the UCEIS, even if further validation is needed to establish thresholds for remission, the clinical relevance of different UCEIS scores, and responsiveness of the UCEIS to change in disease status," they noted.

The CD study was partly funded by Janssen Biotech; Dr. Ferrante was supported by the Belgian Society of Gastrointestinal Endoscopy and by Funds for Scientific Research, Belgium. The authors disclosed serving on advisory committees and review panels of, or serving as consultants and speakers for, multiple pharmaceutical manufacturers, as well as receiving grants or research support from the companies, including Janssen and Abbott. Several authors were employees of Janssen Biotech and Janssen Biologics, the manufacturer of infliximab. One author had no disclosures.

The UCEIS study was funded by Warner Chilcott, and one author was an employee of the company. The authors disclosed serving as consultants, advisers, and/or speakers for, and receiving research grants from, multiple pharmaceutical companies. Several authors had no disclosures.

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