IBD & Intestinal Disorders

Early dual therapy with infliximab and an immunomodulator significantly decreased the 1-year risk of hospitalization and surgery in patients with inflammatory bowel disease, in a cohort study of almost 20,500 patients.

The improvements in hospitalization and surgery rates became apparent as quickly as 5 months after therapy initiation. By 9 months after dual therapy began, there was an 86% decrease in hospitalization and a 92% decrease in surgery compared with the rates in those who had not taken these medications.

The study shows that aggressive treatment of inflammatory bowel disease can reap robust results, Dr. Neena S. Abraham and colleagues reported in the Aug. 29 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.04.051).

The results probably underestimate the potential benefits of dual therapy, wrote Dr. Abraham of the Mayo Clinic, Scottsdale, Ariz., and associates. Only 11% of patients in the database took one of the studied treatment regimens, and of those, most (85%) got an immunomodulator only.

"Given the paucity prescribed dual therapy (8.5%), the dose-response data are even more impressive and suggest that if dual therapy had been initiated earlier, greater benefit may have been observed," the investigators wrote.

The study examined 1-year hospitalization and surgical rates in 20,474 patients with either ulcerative colitis or Crohn’s disease. The patients were all included in a database that covered 176 U.S. Department of Veteran Affairs facilities.

Three treatment protocols were examined: immunomodulator monotherapy, anti–tumor necrosis factor (TNF)-alpha monotherapy with infliximab, and dual therapy with an immunomodulator and infliximab.

Most of the patients (12,432) had ulcerative colitis (UC); the remainder had Crohn’s disease (CD). Most (94%) were male; the mean age was 72 years.

The most common strategy was the anti–TNF-alpha alone (8%). Among patients receiving infliximab, 63% had evidence of induction therapy preceding a maintenance regimen.

"Despite their clear therapeutic benefit, less than 15% of patients with inflammatory bowel disease receive anti-TNF monotherapy, and 40% of patients with active CD receive anti-TNF agents in combination with immunomodulator agents (thiopurines or methotrexate)," they commented.

Most patients (66%) were taking other drugs, including steroids (14%), nonsteroidal anti-inflammatory agents (39%), aspirin (21%), cyclosporine (0.21%), antimetabolites (0.67%), and antibiotics (29%).

A 50% relative reduction in hospitalization occurred at 7.7 months with dual therapy compared with 9 months with immunomodulator monotherapy and 8 months with anti–TNF-alpha therapy. All of these differences were statistically significant after the model was adjusted for diagnosis (UC or CD), smoking status, race/ethnicity, and other medications that could modify the treatment effect.

By 1 year, there was a 45% relative reduction in hospitalization for immunomodulator therapy and a 78% relative reduction with anti–TNF-alpha monotherapy. But patients taking dual therapy reached a similar reduction of 73% by 9 months.

"Results suggested that, if dual therapy had been initiated earlier, perhaps a greater response in the outcome may have been observed," the investigators wrote.

There was a similar beneficial effect on surgeries related to the disorders. In the first year of treatment, there were 276 procedures. By 9 months, there was a 28% risk reduction associated with immunomodulator monotherapy, a 90% reduction associated with anti–TNF-alpha monotherapy, and a 92% reduction associated with dual therapy.

This also suggests that a "greater response may have been observed with earlier initiation of dual therapy," the authors said.

Safety concerns may be one reason for the dearth of these treatment protocols, the authors noted. However, recent long-term safety data suggest that there is a very low risk of mortality associated with them.

"[Five-year] outcome data on infliximab use has failed to demonstrate increased risk of mortality, and, although increased risk of infection was observed, the presence of severe disease and use of prednisone or narcotics carried higher risks," they said, referring to a 2012 study (Am. J. Gastroenterol. 2012;107:1409-22).

A 2011 study also suggested that the benefits of dual therapy outweigh the risks of developing a serious infection or cancer (Clin. J. Gastroenterol. Hepatol. 2012;10:46-51).

Janssen Biotech funded the study. None of the authors reported having any relevant financial disclosures.

msullivan@frontlinemedcom.com

Early dual therapy with infliximab and an immunomodulator significantly decreased the 1-year risk of hospitalization and surgery in patients with inflammatory bowel disease, in a cohort study of almost 20,500 patients.

The improvements in hospitalization and surgery rates became apparent as quickly as 5 months after therapy initiation. By 9 months after dual therapy began, there was an 86% decrease in hospitalization and a 92% decrease in surgery compared with the rates in those who had not taken these medications.

The study shows that aggressive treatment of inflammatory bowel disease can reap robust results, Dr. Neena S. Abraham and colleagues reported in the Aug. 29 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.04.051).

The results probably underestimate the potential benefits of dual therapy, wrote Dr. Abraham of the Mayo Clinic, Scottsdale, Ariz., and associates. Only 11% of patients in the database took one of the studied treatment regimens, and of those, most (85%) got an immunomodulator only.

"Given the paucity prescribed dual therapy (8.5%), the dose-response data are even more impressive and suggest that if dual therapy had been initiated earlier, greater benefit may have been observed," the investigators wrote.

The study examined 1-year hospitalization and surgical rates in 20,474 patients with either ulcerative colitis or Crohn’s disease. The patients were all included in a database that covered 176 U.S. Department of Veteran Affairs facilities.

Three treatment protocols were examined: immunomodulator monotherapy, anti–tumor necrosis factor (TNF)-alpha monotherapy with infliximab, and dual therapy with an immunomodulator and infliximab.

Most of the patients (12,432) had ulcerative colitis (UC); the remainder had Crohn’s disease (CD). Most (94%) were male; the mean age was 72 years.

The most common strategy was the anti–TNF-alpha alone (8%). Among patients receiving infliximab, 63% had evidence of induction therapy preceding a maintenance regimen.

"Despite their clear therapeutic benefit, less than 15% of patients with inflammatory bowel disease receive anti-TNF monotherapy, and 40% of patients with active CD receive anti-TNF agents in combination with immunomodulator agents (thiopurines or methotrexate)," they commented.

Most patients (66%) were taking other drugs, including steroids (14%), nonsteroidal anti-inflammatory agents (39%), aspirin (21%), cyclosporine (0.21%), antimetabolites (0.67%), and antibiotics (29%).

A 50% relative reduction in hospitalization occurred at 7.7 months with dual therapy compared with 9 months with immunomodulator monotherapy and 8 months with anti–TNF-alpha therapy. All of these differences were statistically significant after the model was adjusted for diagnosis (UC or CD), smoking status, race/ethnicity, and other medications that could modify the treatment effect.

By 1 year, there was a 45% relative reduction in hospitalization for immunomodulator therapy and a 78% relative reduction with anti–TNF-alpha monotherapy. But patients taking dual therapy reached a similar reduction of 73% by 9 months.

"Results suggested that, if dual therapy had been initiated earlier, perhaps a greater response in the outcome may have been observed," the investigators wrote.

There was a similar beneficial effect on surgeries related to the disorders. In the first year of treatment, there were 276 procedures. By 9 months, there was a 28% risk reduction associated with immunomodulator monotherapy, a 90% reduction associated with anti–TNF-alpha monotherapy, and a 92% reduction associated with dual therapy.

This also suggests that a "greater response may have been observed with earlier initiation of dual therapy," the authors said.

Safety concerns may be one reason for the dearth of these treatment protocols, the authors noted. However, recent long-term safety data suggest that there is a very low risk of mortality associated with them.

"[Five-year] outcome data on infliximab use has failed to demonstrate increased risk of mortality, and, although increased risk of infection was observed, the presence of severe disease and use of prednisone or narcotics carried higher risks," they said, referring to a 2012 study (Am. J. Gastroenterol. 2012;107:1409-22).

A 2011 study also suggested that the benefits of dual therapy outweigh the risks of developing a serious infection or cancer (Clin. J. Gastroenterol. Hepatol. 2012;10:46-51).

Janssen Biotech funded the study. None of the authors reported having any relevant financial disclosures.

msullivan@frontlinemedcom.com

Early dual therapy with infliximab and an immunomodulator significantly decreased the 1-year risk of hospitalization and surgery in patients with inflammatory bowel disease, in a cohort study of almost 20,500 patients.

The improvements in hospitalization and surgery rates became apparent as quickly as 5 months after therapy initiation. By 9 months after dual therapy began, there was an 86% decrease in hospitalization and a 92% decrease in surgery compared with the rates in those who had not taken these medications.

The study shows that aggressive treatment of inflammatory bowel disease can reap robust results, Dr. Neena S. Abraham and colleagues reported in the Aug. 29 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.04.051).

The results probably underestimate the potential benefits of dual therapy, wrote Dr. Abraham of the Mayo Clinic, Scottsdale, Ariz., and associates. Only 11% of patients in the database took one of the studied treatment regimens, and of those, most (85%) got an immunomodulator only.

"Given the paucity prescribed dual therapy (8.5%), the dose-response data are even more impressive and suggest that if dual therapy had been initiated earlier, greater benefit may have been observed," the investigators wrote.

The study examined 1-year hospitalization and surgical rates in 20,474 patients with either ulcerative colitis or Crohn’s disease. The patients were all included in a database that covered 176 U.S. Department of Veteran Affairs facilities.

Three treatment protocols were examined: immunomodulator monotherapy, anti–tumor necrosis factor (TNF)-alpha monotherapy with infliximab, and dual therapy with an immunomodulator and infliximab.

Most of the patients (12,432) had ulcerative colitis (UC); the remainder had Crohn’s disease (CD). Most (94%) were male; the mean age was 72 years.

The most common strategy was the anti–TNF-alpha alone (8%). Among patients receiving infliximab, 63% had evidence of induction therapy preceding a maintenance regimen.

"Despite their clear therapeutic benefit, less than 15% of patients with inflammatory bowel disease receive anti-TNF monotherapy, and 40% of patients with active CD receive anti-TNF agents in combination with immunomodulator agents (thiopurines or methotrexate)," they commented.

Most patients (66%) were taking other drugs, including steroids (14%), nonsteroidal anti-inflammatory agents (39%), aspirin (21%), cyclosporine (0.21%), antimetabolites (0.67%), and antibiotics (29%).

A 50% relative reduction in hospitalization occurred at 7.7 months with dual therapy compared with 9 months with immunomodulator monotherapy and 8 months with anti–TNF-alpha therapy. All of these differences were statistically significant after the model was adjusted for diagnosis (UC or CD), smoking status, race/ethnicity, and other medications that could modify the treatment effect.

By 1 year, there was a 45% relative reduction in hospitalization for immunomodulator therapy and a 78% relative reduction with anti–TNF-alpha monotherapy. But patients taking dual therapy reached a similar reduction of 73% by 9 months.

"Results suggested that, if dual therapy had been initiated earlier, perhaps a greater response in the outcome may have been observed," the investigators wrote.

There was a similar beneficial effect on surgeries related to the disorders. In the first year of treatment, there were 276 procedures. By 9 months, there was a 28% risk reduction associated with immunomodulator monotherapy, a 90% reduction associated with anti–TNF-alpha monotherapy, and a 92% reduction associated with dual therapy.

This also suggests that a "greater response may have been observed with earlier initiation of dual therapy," the authors said.

Safety concerns may be one reason for the dearth of these treatment protocols, the authors noted. However, recent long-term safety data suggest that there is a very low risk of mortality associated with them.

"[Five-year] outcome data on infliximab use has failed to demonstrate increased risk of mortality, and, although increased risk of infection was observed, the presence of severe disease and use of prednisone or narcotics carried higher risks," they said, referring to a 2012 study (Am. J. Gastroenterol. 2012;107:1409-22).

A 2011 study also suggested that the benefits of dual therapy outweigh the risks of developing a serious infection or cancer (Clin. J. Gastroenterol. Hepatol. 2012;10:46-51).

Janssen Biotech funded the study. None of the authors reported having any relevant financial disclosures.

msullivan@frontlinemedcom.com

The humanized monoclonal antibody vedolizumab is more effective than placebo for induction and maintenance therapy in both ulcerative colitis and Crohn’s disease, according to two separate randomized, controlled phase III studies: GEMINI 1 and GEMINI 2.

The findings from the double-blind, multinational studies were published in the Aug. 22 issue of the New England Journal of Medicine.

GEMINI 1

In GEMINI 1, the clinical response rates at 6 weeks in 374 patients (cohort 1) with active ulcerative colitis who were randomized to receive either induction therapy with vedolizumab or placebo were 47.1% and 25.5%, respectively (P less than .001). In 521 patients (cohort 2) who received open-label vedolizumab, the clinical response rate at 6 weeks was 44.3%.

In a trial of maintenance therapy, those patients from both cohorts who responded to vedolizumab at week 6 were then randomized to receive either vedolizumab or placebo every 4 or 8 weeks for up to 52 weeks. The clinical remission rates at 52 weeks were 44.8% in the group that received vedolizumab every 4 weeks, 41.8% in the group that received it every 8 weeks, and 15.9% among the patients who were switched to placebo, Dr. Brian G. Feagan of the University of Western Ontario, London, and his colleagues reported on behalf of the GEMINI 1 Study Group.

Patients in the vedolizumab groups were treated with 300 mg IV at weeks 0 and 2. Clinical response was defined as a reduction of at least 3 points in the 0- to 12-point Mayo Clinic score and a decrease of at least 30% from the baseline score, along with a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. The secondary outcome of clinical remission was defined as a Mayo Clinic score of 2 or less, with no subscore higher than 1, along with mucosal healing, defined by an endoscopic subscore of 0 or 1, the investigators said (N. Engl. J. Med. 2013;369:699-710).

The GEMINI 1 researchers noted that "all prespecified, primary and secondary outcomes in the trial of induction and maintenance therapy were superior in vedolizumab-treated patients versus those who received placebo," and added that longitudinal assessment of a number of factors, such as Mayo Clinic scores and use or dose of glucocorticoids, provided further evidence of a treatment benefit.

Furthermore, disease had been refractory to other treatments in many patients, they noted.

While the study was not designed to identify the time of the maximal effect of treatment as induction therapy, or a minimally effective dose regimen, it appears that treatment every 8 weeks may be an acceptable starting regimen – with dose intensification if needed, they said. "Vedolizumab is effective as both induction and maintenance therapy for patients with moderately to severely active ulcerative colitis," they concluded.

GEMINI 2

In GEMINI 2, the clinical remission rates at 6 weeks in 368 patients with active Crohn’s disease who were randomized to receive either induction therapy with vedolizumab or placebo were 14.5% and 6.8%, respectively (P = .02), and a total of 31.4% and 25.7% of patients, respectively (P = .023), had a Crohn’s Disease Activity Index-100 (CDAI-100) response, defined as a decrease in the CDAI score of at least 100 points. Of 747 patients who received open-label vedolizumab, 17.7% had a clinical remission and 34.4% had a CDAI-100 response at 6 weeks.

Those patients who responded to vedolizumab in the induction phase were randomly assigned to receive either placebo or maintenance treatment every 4 or 8 weeks until week 52. The clinical remission rates at 52 weeks were 36.4% in the group that received the drug every 4 weeks, 39.0% in the group receiving it every 8 weeks, and 21.6% in the placebo group, Dr. William J. Sandborn of the University of California, San Diego, La Jolla, and his colleagues reported on behalf of the GEMINI 2 Study Group (N. Engl. J. Med. 2013; 369:711-21).

As in GEMINI 1, patients in GEMINI 2 who were assigned to the vedolizumab groups were treated with 300 mg IV at weeks 0 and 2. In GEMINI 2, clinical remission was defined as a CDAI score of 150 or less.

In GEMINI 1, the frequency of adverse events was similar in both the treatment and placebo groups, whereas in GEMINI 2, vedolizumab, compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%), the investigators said.

Patients in both GEMINI 1 and 2 were aged 18-80 years who were enrolled between 2008 and 2012 through more than 200 participating medical centers in more than 30 countries.

The findings are important because existing medical therapies for ulcerative colitis and Crohn’s disease have significant limitations, including toxic effects, and new treatment strategies are needed, the investigators said.

The GEMINI 2 investigators noted that patients with moderately to severely active Crohn’s disease, in whom conventional therapy failed, were more likely than those receiving placebo to experience remission at 6 weeks. They were not more likely to have a CDAI-100 response, however.

While the modest effect of treatment on induction of clinical remission, as well as the nonsignificant effect on the CDAI-100, require consideration, and while questions remain about which specific patients with Crohn’s disease may derive the most benefit from vedolizumab and about potential synergistic effects of combining vedolizumab with immunosuppressive agents, the findings nonetheless suggest a role for vedolizumab in Crohn’s disease, they noted.

"In an analysis of patients who had a response to induction therapy with vedolizumab, the rates of clinical remission, CDAI-100 response, and glucocorticoid-free remission at week 52 were higher among patients receiving vedolizumab every 8 weeks or every 4 weeks than among patients who were switched to placebo," they said.

GEMINI 1 and GEMINI 2 were funded by Millennium Pharmaceuticals. The authors disclosed multiple potential conflicts of interest; the details are available with the full text of the articles at NEJM.org.

The humanized monoclonal antibody vedolizumab is more effective than placebo for induction and maintenance therapy in both ulcerative colitis and Crohn’s disease, according to two separate randomized, controlled phase III studies: GEMINI 1 and GEMINI 2.

The findings from the double-blind, multinational studies were published in the Aug. 22 issue of the New England Journal of Medicine.

GEMINI 1

In GEMINI 1, the clinical response rates at 6 weeks in 374 patients (cohort 1) with active ulcerative colitis who were randomized to receive either induction therapy with vedolizumab or placebo were 47.1% and 25.5%, respectively (P less than .001). In 521 patients (cohort 2) who received open-label vedolizumab, the clinical response rate at 6 weeks was 44.3%.

In a trial of maintenance therapy, those patients from both cohorts who responded to vedolizumab at week 6 were then randomized to receive either vedolizumab or placebo every 4 or 8 weeks for up to 52 weeks. The clinical remission rates at 52 weeks were 44.8% in the group that received vedolizumab every 4 weeks, 41.8% in the group that received it every 8 weeks, and 15.9% among the patients who were switched to placebo, Dr. Brian G. Feagan of the University of Western Ontario, London, and his colleagues reported on behalf of the GEMINI 1 Study Group.

Patients in the vedolizumab groups were treated with 300 mg IV at weeks 0 and 2. Clinical response was defined as a reduction of at least 3 points in the 0- to 12-point Mayo Clinic score and a decrease of at least 30% from the baseline score, along with a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. The secondary outcome of clinical remission was defined as a Mayo Clinic score of 2 or less, with no subscore higher than 1, along with mucosal healing, defined by an endoscopic subscore of 0 or 1, the investigators said (N. Engl. J. Med. 2013;369:699-710).

The GEMINI 1 researchers noted that "all prespecified, primary and secondary outcomes in the trial of induction and maintenance therapy were superior in vedolizumab-treated patients versus those who received placebo," and added that longitudinal assessment of a number of factors, such as Mayo Clinic scores and use or dose of glucocorticoids, provided further evidence of a treatment benefit.

Furthermore, disease had been refractory to other treatments in many patients, they noted.

While the study was not designed to identify the time of the maximal effect of treatment as induction therapy, or a minimally effective dose regimen, it appears that treatment every 8 weeks may be an acceptable starting regimen – with dose intensification if needed, they said. "Vedolizumab is effective as both induction and maintenance therapy for patients with moderately to severely active ulcerative colitis," they concluded.

GEMINI 2

In GEMINI 2, the clinical remission rates at 6 weeks in 368 patients with active Crohn’s disease who were randomized to receive either induction therapy with vedolizumab or placebo were 14.5% and 6.8%, respectively (P = .02), and a total of 31.4% and 25.7% of patients, respectively (P = .023), had a Crohn’s Disease Activity Index-100 (CDAI-100) response, defined as a decrease in the CDAI score of at least 100 points. Of 747 patients who received open-label vedolizumab, 17.7% had a clinical remission and 34.4% had a CDAI-100 response at 6 weeks.

Those patients who responded to vedolizumab in the induction phase were randomly assigned to receive either placebo or maintenance treatment every 4 or 8 weeks until week 52. The clinical remission rates at 52 weeks were 36.4% in the group that received the drug every 4 weeks, 39.0% in the group receiving it every 8 weeks, and 21.6% in the placebo group, Dr. William J. Sandborn of the University of California, San Diego, La Jolla, and his colleagues reported on behalf of the GEMINI 2 Study Group (N. Engl. J. Med. 2013; 369:711-21).

As in GEMINI 1, patients in GEMINI 2 who were assigned to the vedolizumab groups were treated with 300 mg IV at weeks 0 and 2. In GEMINI 2, clinical remission was defined as a CDAI score of 150 or less.

In GEMINI 1, the frequency of adverse events was similar in both the treatment and placebo groups, whereas in GEMINI 2, vedolizumab, compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%), the investigators said.

Patients in both GEMINI 1 and 2 were aged 18-80 years who were enrolled between 2008 and 2012 through more than 200 participating medical centers in more than 30 countries.

The findings are important because existing medical therapies for ulcerative colitis and Crohn’s disease have significant limitations, including toxic effects, and new treatment strategies are needed, the investigators said.

The GEMINI 2 investigators noted that patients with moderately to severely active Crohn’s disease, in whom conventional therapy failed, were more likely than those receiving placebo to experience remission at 6 weeks. They were not more likely to have a CDAI-100 response, however.

While the modest effect of treatment on induction of clinical remission, as well as the nonsignificant effect on the CDAI-100, require consideration, and while questions remain about which specific patients with Crohn’s disease may derive the most benefit from vedolizumab and about potential synergistic effects of combining vedolizumab with immunosuppressive agents, the findings nonetheless suggest a role for vedolizumab in Crohn’s disease, they noted.

"In an analysis of patients who had a response to induction therapy with vedolizumab, the rates of clinical remission, CDAI-100 response, and glucocorticoid-free remission at week 52 were higher among patients receiving vedolizumab every 8 weeks or every 4 weeks than among patients who were switched to placebo," they said.

GEMINI 1 and GEMINI 2 were funded by Millennium Pharmaceuticals. The authors disclosed multiple potential conflicts of interest; the details are available with the full text of the articles at NEJM.org.

The humanized monoclonal antibody vedolizumab is more effective than placebo for induction and maintenance therapy in both ulcerative colitis and Crohn’s disease, according to two separate randomized, controlled phase III studies: GEMINI 1 and GEMINI 2.

The findings from the double-blind, multinational studies were published in the Aug. 22 issue of the New England Journal of Medicine.

GEMINI 1

In GEMINI 1, the clinical response rates at 6 weeks in 374 patients (cohort 1) with active ulcerative colitis who were randomized to receive either induction therapy with vedolizumab or placebo were 47.1% and 25.5%, respectively (P less than .001). In 521 patients (cohort 2) who received open-label vedolizumab, the clinical response rate at 6 weeks was 44.3%.

In a trial of maintenance therapy, those patients from both cohorts who responded to vedolizumab at week 6 were then randomized to receive either vedolizumab or placebo every 4 or 8 weeks for up to 52 weeks. The clinical remission rates at 52 weeks were 44.8% in the group that received vedolizumab every 4 weeks, 41.8% in the group that received it every 8 weeks, and 15.9% among the patients who were switched to placebo, Dr. Brian G. Feagan of the University of Western Ontario, London, and his colleagues reported on behalf of the GEMINI 1 Study Group.

Patients in the vedolizumab groups were treated with 300 mg IV at weeks 0 and 2. Clinical response was defined as a reduction of at least 3 points in the 0- to 12-point Mayo Clinic score and a decrease of at least 30% from the baseline score, along with a decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. The secondary outcome of clinical remission was defined as a Mayo Clinic score of 2 or less, with no subscore higher than 1, along with mucosal healing, defined by an endoscopic subscore of 0 or 1, the investigators said (N. Engl. J. Med. 2013;369:699-710).

The GEMINI 1 researchers noted that "all prespecified, primary and secondary outcomes in the trial of induction and maintenance therapy were superior in vedolizumab-treated patients versus those who received placebo," and added that longitudinal assessment of a number of factors, such as Mayo Clinic scores and use or dose of glucocorticoids, provided further evidence of a treatment benefit.

Furthermore, disease had been refractory to other treatments in many patients, they noted.

While the study was not designed to identify the time of the maximal effect of treatment as induction therapy, or a minimally effective dose regimen, it appears that treatment every 8 weeks may be an acceptable starting regimen – with dose intensification if needed, they said. "Vedolizumab is effective as both induction and maintenance therapy for patients with moderately to severely active ulcerative colitis," they concluded.

GEMINI 2

In GEMINI 2, the clinical remission rates at 6 weeks in 368 patients with active Crohn’s disease who were randomized to receive either induction therapy with vedolizumab or placebo were 14.5% and 6.8%, respectively (P = .02), and a total of 31.4% and 25.7% of patients, respectively (P = .023), had a Crohn’s Disease Activity Index-100 (CDAI-100) response, defined as a decrease in the CDAI score of at least 100 points. Of 747 patients who received open-label vedolizumab, 17.7% had a clinical remission and 34.4% had a CDAI-100 response at 6 weeks.

Those patients who responded to vedolizumab in the induction phase were randomly assigned to receive either placebo or maintenance treatment every 4 or 8 weeks until week 52. The clinical remission rates at 52 weeks were 36.4% in the group that received the drug every 4 weeks, 39.0% in the group receiving it every 8 weeks, and 21.6% in the placebo group, Dr. William J. Sandborn of the University of California, San Diego, La Jolla, and his colleagues reported on behalf of the GEMINI 2 Study Group (N. Engl. J. Med. 2013; 369:711-21).

As in GEMINI 1, patients in GEMINI 2 who were assigned to the vedolizumab groups were treated with 300 mg IV at weeks 0 and 2. In GEMINI 2, clinical remission was defined as a CDAI score of 150 or less.

In GEMINI 1, the frequency of adverse events was similar in both the treatment and placebo groups, whereas in GEMINI 2, vedolizumab, compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%), the investigators said.

Patients in both GEMINI 1 and 2 were aged 18-80 years who were enrolled between 2008 and 2012 through more than 200 participating medical centers in more than 30 countries.

The findings are important because existing medical therapies for ulcerative colitis and Crohn’s disease have significant limitations, including toxic effects, and new treatment strategies are needed, the investigators said.

The GEMINI 2 investigators noted that patients with moderately to severely active Crohn’s disease, in whom conventional therapy failed, were more likely than those receiving placebo to experience remission at 6 weeks. They were not more likely to have a CDAI-100 response, however.

While the modest effect of treatment on induction of clinical remission, as well as the nonsignificant effect on the CDAI-100, require consideration, and while questions remain about which specific patients with Crohn’s disease may derive the most benefit from vedolizumab and about potential synergistic effects of combining vedolizumab with immunosuppressive agents, the findings nonetheless suggest a role for vedolizumab in Crohn’s disease, they noted.

"In an analysis of patients who had a response to induction therapy with vedolizumab, the rates of clinical remission, CDAI-100 response, and glucocorticoid-free remission at week 52 were higher among patients receiving vedolizumab every 8 weeks or every 4 weeks than among patients who were switched to placebo," they said.

GEMINI 1 and GEMINI 2 were funded by Millennium Pharmaceuticals. The authors disclosed multiple potential conflicts of interest; the details are available with the full text of the articles at NEJM.org.

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

emechcatie@frontlinemedcom.com

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

emechcatie@frontlinemedcom.com

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

A study that evaluated bacterial populations present in the submucosal intestinal tissue of patients with Crohn’s and controls provides evidence suggesting there may be "at least two distinct populations or biotypes within the Crohn’s disease spectrum and the existence of a submucosal microbiome in both health and disease," according to the investigators.

"Our results, if corroborated by larger population studies and development of methodologies applicable to a clinical setting, could revolutionize the diagnosis, management, and treatment of Crohn’s disease," Rodrick J. Chiodini, Ph.D., and his coauthors concluded in the study, which was published in August (J. Clin. Gastroenterol. 2013; 47:612-20). "It would allow the identification of patient subpopulations and biotypes within the Crohn’s disease spectrum and the application of targeted chemotherapeutic treatments that go beyond supportive in nature," they added.

The study compared submucosal intestinal tissue samples of 14 patients with Crohn’s disease obtained during surgery with that of six patients undergoing intestinal surgery for reasons that did not include inflammatory bowel disease. To detect the presence of bacterial pathogens, they evaluated submucosal intestinal tissue that was directly associated with intestinal inflammation and compared the findings to those of the mucosal lining, using quantitative genetic methods that detected 32 virulence- and transposon-associated genes and to determine total submucosal bacterial counts.

"The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease."

They determined that there was a "normal" submucosal bacterial community (microbiome) in both health and disease that was different from the bacteria present in the mucosal and luminal populations, Dr. Chiodini explained in an interview. They also determined that total bacterial counts within the diseased Crohn’s tissues were several hundredfold higher than the counts found in normal tissue, added Dr. Chiodini, formerly of the department of internal medicine, Texas Tech University Health Sciences Center, El Paso.

In addition to increased total submucosal bacteria counts, Proteobacteria-associated adherence/virulence genes were detected in the submucosa of 43% of patients with Crohn’s disease, a statistical significantly higher rate when compared with that from the mucosa of the same patient and controls. Mycobacterium-associated* transposons were detected in the submucosa of 50% of the patients with Crohn’s disease, also at a significantly higher rate than the mucosa and controls.

These biotypes were found to be mutually exclusive: Invasion/adherence genes were not found in patients in which Mycobacterium-associated* transposons were detected and vice versa, Dr. Chiodini said in the interview.

"There is now overwhelming evidence that enteric bacteria play a major role in the pathogenesis of Crohn’s disease, either as causative agents or mitigating factors," he added. "As such, a great deal of effort has been devoted to the examination of the bacteria present within the intestinal lumen and associated with the mucosal lining of the intestine."

This study is the first to look at bacterial populations within the submucosa, where the inflammation is actually occurring, he noted.

While their results need to be corroborated with larger patient populations, "the data presented herein also provide the first objective evidence that Crohn’s disease may not have a single etiology," he continued. "The ability to subgroup patient populations may have a profound effect on the diagnosis, management, and ultimate cure of the disease. If clinicians can gain a better understanding of the microbes that are directly associated with intestinal inflammation, it will give them a greater understanding of the intestinal ecology and allow them to better manage the inflammation, thereby improving the prognosis of patients."

Dr. Chiodini has recently relocated to St. Vincent’s Health Care and Montana State University, Billings.

None of the authors had disclosures. The study was supported in part by the Texas Tech University Health Sciences Center, the Lizanell and Colbert Coldwell Foundation, the CAMC Health Education and Research Institute, and the Crohn’s Disease Initiative.

emechcatie@frontlinemedcom.com

*Correction 8/20/2013: An earlier version of this story missnamed the bacteria.

Elevated plasma levels of the biomarker ST2, measured 2 weeks after allogeneic hematopoietic stem-cell transplantation, predicted which patients who develop graft-vs.-host disease are unlikely to respond to treatment and are thus at high risk of death within 6 months, according to a report published online Aug. 8 in the New England Journal of Medicine.

Approximately half of allogeneic stem-cell transplant recipients develop acute GVHD, and those who don’t respond to high-dose systemic glucocorticoids within 1 month are at high risk of dying within 6 months without relapse of the primary disease for which the transplant was performed. At present, it is difficult to predict which patients will not respond to glucocorticoids.

Courtesy JAAD:38(3), 369-92; 1998

Adding a patient’s ST2 (suppression of tumorigenicity 2) level to the clinical grade and the target-organ stage of GVHD significantly improves risk prediction, particularly in the important subgroup of patients who have lower-GI GVHD, said Dr. Mark T. Vander Lugt of the department of pediatrics, University of Michigan, Ann Arbor, and his associates.

"The improved risk stratification of patients with GVHD with the use of ST2 may permit early evaluation of additional therapies, before the development of resistant disease," they wrote (N. Engl. J. Med. 2013 Aug. 8;369:529-39 [doi:10.1056/NEJMoa1213299]).

This early identification may also "permit more stringent monitoring and preemptive interventions."

ST2, a recently discovered member of the interleukin-1 receptor family, is expressed on hematopoietic cells that play a role in diseases mediated by type-2 helper T cells and is also secreted by endothelial cells, epithelial cells, and fibroblasts in response to inflammatory stimuli.

Dr. Vander Lugt and his colleagues assessed numerous candidate plasma biomarkers to determine which, if any, showed the strongest association with nonresponse to GVHD therapy and could thus be used as risk predictors.

They began by testing plasma samples collected 16 days after transplantation from 10 patients who went on to have a complete response to GVHD therapy and 10 who went on to have progressive GVHD. They identified and quantified 571 proteins in these samples, and found that 197 of them were overexpressed by a factor of at least 1.5 in the patients with progressive GVHD. Twelve of these proteins, in addition to ST2, could be measured using commercially available antibodies suitable for ELISA.

ST2 was the single most accurate biomarker at discriminating between plasma samples from patients who responded to GVHD therapy and plasma samples from patients who did not. The six other best biomarkers were then assessed as a panel and compared against ST2 in samples taken from 381 patients at the onset of GVHD.

The ST2 level was found to be superior to the six-biomarker panel in predicting which patients with GVHD would not respond to glucocorticoids within a month of initiating the treatment, which is an accepted surrogate 6-month mortality. It also was the best predictive biomarker when tested further in three independent cohorts totaling 673 patients, the investigators said.

Patients with high ST2 levels were 2.3 times more likely than those with low ST2 levels to develop treatment-resistant GVHD, and 3.7 times as likely to die within 6 months.

Moreover, "when measured as early as day 14 after transplantation, ST2 concentration was a better predictor of the risk of death than were the other known risk factors, including the age of the recipient, conditioning intensity, donor source, and HLA [human leukocyte antigens] match," Dr. Vander Lugt and his associates wrote.

"We believe that our results may affect the assessment of GVHD risk before the development of GVHD and at the onset of the clinical signs of GVHD; however, a generalizable definition of high risk has yet to be developed and will require larger studies," they added.

The study was supported by grants from the National Institutes of Health. The University of Michigan has licensed a pending patent application for the biomarker test to ViraCor and any revenue will be shared with the inventors at the University of Michigan and the Fred Hutchinson Cancer Research Center, Seattle.

Elevated plasma levels of the biomarker ST2, measured 2 weeks after allogeneic hematopoietic stem-cell transplantation, predicted which patients who develop graft-vs.-host disease are unlikely to respond to treatment and are thus at high risk of death within 6 months, according to a report published online Aug. 8 in the New England Journal of Medicine.

Approximately half of allogeneic stem-cell transplant recipients develop acute GVHD, and those who don’t respond to high-dose systemic glucocorticoids within 1 month are at high risk of dying within 6 months without relapse of the primary disease for which the transplant was performed. At present, it is difficult to predict which patients will not respond to glucocorticoids.

Courtesy JAAD:38(3), 369-92; 1998

Adding a patient’s ST2 (suppression of tumorigenicity 2) level to the clinical grade and the target-organ stage of GVHD significantly improves risk prediction, particularly in the important subgroup of patients who have lower-GI GVHD, said Dr. Mark T. Vander Lugt of the department of pediatrics, University of Michigan, Ann Arbor, and his associates.

"The improved risk stratification of patients with GVHD with the use of ST2 may permit early evaluation of additional therapies, before the development of resistant disease," they wrote (N. Engl. J. Med. 2013 Aug. 8;369:529-39 [doi:10.1056/NEJMoa1213299]).

This early identification may also "permit more stringent monitoring and preemptive interventions."

ST2, a recently discovered member of the interleukin-1 receptor family, is expressed on hematopoietic cells that play a role in diseases mediated by type-2 helper T cells and is also secreted by endothelial cells, epithelial cells, and fibroblasts in response to inflammatory stimuli.

Dr. Vander Lugt and his colleagues assessed numerous candidate plasma biomarkers to determine which, if any, showed the strongest association with nonresponse to GVHD therapy and could thus be used as risk predictors.

They began by testing plasma samples collected 16 days after transplantation from 10 patients who went on to have a complete response to GVHD therapy and 10 who went on to have progressive GVHD. They identified and quantified 571 proteins in these samples, and found that 197 of them were overexpressed by a factor of at least 1.5 in the patients with progressive GVHD. Twelve of these proteins, in addition to ST2, could be measured using commercially available antibodies suitable for ELISA.

ST2 was the single most accurate biomarker at discriminating between plasma samples from patients who responded to GVHD therapy and plasma samples from patients who did not. The six other best biomarkers were then assessed as a panel and compared against ST2 in samples taken from 381 patients at the onset of GVHD.

The ST2 level was found to be superior to the six-biomarker panel in predicting which patients with GVHD would not respond to glucocorticoids within a month of initiating the treatment, which is an accepted surrogate 6-month mortality. It also was the best predictive biomarker when tested further in three independent cohorts totaling 673 patients, the investigators said.

Patients with high ST2 levels were 2.3 times more likely than those with low ST2 levels to develop treatment-resistant GVHD, and 3.7 times as likely to die within 6 months.

Moreover, "when measured as early as day 14 after transplantation, ST2 concentration was a better predictor of the risk of death than were the other known risk factors, including the age of the recipient, conditioning intensity, donor source, and HLA [human leukocyte antigens] match," Dr. Vander Lugt and his associates wrote.

"We believe that our results may affect the assessment of GVHD risk before the development of GVHD and at the onset of the clinical signs of GVHD; however, a generalizable definition of high risk has yet to be developed and will require larger studies," they added.

The study was supported by grants from the National Institutes of Health. The University of Michigan has licensed a pending patent application for the biomarker test to ViraCor and any revenue will be shared with the inventors at the University of Michigan and the Fred Hutchinson Cancer Research Center, Seattle.

Elevated plasma levels of the biomarker ST2, measured 2 weeks after allogeneic hematopoietic stem-cell transplantation, predicted which patients who develop graft-vs.-host disease are unlikely to respond to treatment and are thus at high risk of death within 6 months, according to a report published online Aug. 8 in the New England Journal of Medicine.

Approximately half of allogeneic stem-cell transplant recipients develop acute GVHD, and those who don’t respond to high-dose systemic glucocorticoids within 1 month are at high risk of dying within 6 months without relapse of the primary disease for which the transplant was performed. At present, it is difficult to predict which patients will not respond to glucocorticoids.

Courtesy JAAD:38(3), 369-92; 1998

Adding a patient’s ST2 (suppression of tumorigenicity 2) level to the clinical grade and the target-organ stage of GVHD significantly improves risk prediction, particularly in the important subgroup of patients who have lower-GI GVHD, said Dr. Mark T. Vander Lugt of the department of pediatrics, University of Michigan, Ann Arbor, and his associates.

"The improved risk stratification of patients with GVHD with the use of ST2 may permit early evaluation of additional therapies, before the development of resistant disease," they wrote (N. Engl. J. Med. 2013 Aug. 8;369:529-39 [doi:10.1056/NEJMoa1213299]).

This early identification may also "permit more stringent monitoring and preemptive interventions."

ST2, a recently discovered member of the interleukin-1 receptor family, is expressed on hematopoietic cells that play a role in diseases mediated by type-2 helper T cells and is also secreted by endothelial cells, epithelial cells, and fibroblasts in response to inflammatory stimuli.

Dr. Vander Lugt and his colleagues assessed numerous candidate plasma biomarkers to determine which, if any, showed the strongest association with nonresponse to GVHD therapy and could thus be used as risk predictors.

They began by testing plasma samples collected 16 days after transplantation from 10 patients who went on to have a complete response to GVHD therapy and 10 who went on to have progressive GVHD. They identified and quantified 571 proteins in these samples, and found that 197 of them were overexpressed by a factor of at least 1.5 in the patients with progressive GVHD. Twelve of these proteins, in addition to ST2, could be measured using commercially available antibodies suitable for ELISA.

ST2 was the single most accurate biomarker at discriminating between plasma samples from patients who responded to GVHD therapy and plasma samples from patients who did not. The six other best biomarkers were then assessed as a panel and compared against ST2 in samples taken from 381 patients at the onset of GVHD.

The ST2 level was found to be superior to the six-biomarker panel in predicting which patients with GVHD would not respond to glucocorticoids within a month of initiating the treatment, which is an accepted surrogate 6-month mortality. It also was the best predictive biomarker when tested further in three independent cohorts totaling 673 patients, the investigators said.

Patients with high ST2 levels were 2.3 times more likely than those with low ST2 levels to develop treatment-resistant GVHD, and 3.7 times as likely to die within 6 months.

Moreover, "when measured as early as day 14 after transplantation, ST2 concentration was a better predictor of the risk of death than were the other known risk factors, including the age of the recipient, conditioning intensity, donor source, and HLA [human leukocyte antigens] match," Dr. Vander Lugt and his associates wrote.

"We believe that our results may affect the assessment of GVHD risk before the development of GVHD and at the onset of the clinical signs of GVHD; however, a generalizable definition of high risk has yet to be developed and will require larger studies," they added.

The study was supported by grants from the National Institutes of Health. The University of Michigan has licensed a pending patent application for the biomarker test to ViraCor and any revenue will be shared with the inventors at the University of Michigan and the Fred Hutchinson Cancer Research Center, Seattle.

VAIL, COLO. – The strategy of a short course of probiotics prescribed to prevent development of Clostridium difficile–associated diarrhea in patients on antibiotic therapy for any of myriad indications is attracting serious attention in both pediatrics and adult medicine.

Interest in this low-cost and demonstrably low-risk preventive strategy has been driven by a recent favorable meta-analysis by the Cochrane Collaboration.

The Cochrane analysis included all 23 randomized controlled trials of probiotics for the prevention of C. difficile–associated diarrhea in adults or children taking antibiotics. The trials, three of which were conducted in children, included 4,213 subjects, none of whom were immunocompromised, severely ill, or had an underlying gastrointestinal disorder.

The incidence of C. difficile–associated diarrhea was 2.0% in patients randomized to probiotics, compared with 5.5% in controls, for a highly significant 64% reduction in risk. Moreover, the risk of adverse GI events such as abdominal cramping, nausea, fever, taste disturbance, or flatulence was reduced by 20% in the probiotics group (Cochrane Database Syst. Rev. 2013 May 31 [doi: 10.1002/14651858.CD006095.pub3]).

The benefit of prophylactic probiotics was similar in magnitude in children and adults.

"Moderate-quality evidence suggests that probiotics are both safe and effective for preventing C. difficile–associated diarrhea when used along with antibiotics in patients who are not immunocompromised or severely debilitated," the Cochrane investigators concluded.

Neither the current American College of Gastroenterology practice guidelines on C. difficile–associated diarrhea (Am. J. Gastroenterol. 2013;108:478-98) nor the Infectious Diseases Society of America guidelines (Infect. Control Hosp. Epidemiol. 2010;31:431-55) recommend using prophylactic probiotics. However, both guidelines were published before the Cochrane meta-analysis was released, Dr. Samuel R. Dominguez pointed out at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

"Interestingly, a larger effect size was seen in studies of probiotics that contained multiple species compared to a single species, although the data set wasn’t large enough for investigators to be able to look at different specific formulations," added Dr. Dominguez, a pediatric infectious diseases specialist at the University of Colorado, Denver.

He noted that the incidence, severity, and mortality of C. difficile infections have increased dramatically since 2000. Even in children, a population traditionally considered at low risk, a recent population-based study conducted in Olmsted County, Minn., by investigators at the Mayo Clinic concluded that the age- and gender-adjusted incidence of C. difficile infection jumped nearly 13-fold from 1991 to 2009, when it reached 32.6 per 100,000 persons. Three-quarters of the 92 cases were community acquired. Prior studies of C. difficile disease in children may have underestimated the incidence because they were largely based on hospital-acquired cases (Clin. Infect. Dis. 2013;56:1401-6).

Another recent study highlights the serious nature of C. difficile in children, Dr. Dominguez continued. This retrospective cohort study conducted at 41 children’s hospitals included 4,474 patients hospitalized with C. difficile infection and 8,821 matched controls. The in-hospital mortality rate was 1.43% in children with C. difficile infection, compared with 0.66% in controls. In the subgroup of children with hospital-onset C. difficile infection, the mortality risk was an adjusted 6.7-fold higher than in matched controls.

Patients with community-onset C. difficile infection had a mean hospital length of stay that was 5.6 days longer and total hospital costs that were $18,900 greater than those of controls. In patients with hospital-onset C. difficile infection, the differences were even more dramatic: a mean 21.6-day longer length of stay than for controls, and a $93,600 greater hospital cost (Clin. Infect. Dis. 2013;57:1-8).

Dr. Dominguez said that although there is no set policy at Children’s Hospital, his own practice is to recommend probiotics to healthy children who are going to be taking antibiotics.

At a separate conference devoted to adult medicine, Dr. Mel L. Anderson cited both the Cochrane Collaboration meta-analysis and a separate one led by investigators at Toronto’s Hospital for Sick Children that concluded probiotics reduced the incidence of C. difficile–associated diarrhea by 66% (Ann. Intern. Med. 2012;157:878-88).

"If you look at these randomized controlled trials, I think the evidence is fairly convincing. And it’s not an expensive treatment. We use a lot of it in our inpatient service to reduce the risk of antibiotic-associated diarrhea, and C. difficile in particular," said Dr. Anderson, chief of the hospital medicine section at the Denver VA Medical Center.

Prophylactic probiotics are not for the surgical patient who is merely getting a dose or two of perioperative antibiotic coverage. But the preventive therapy is worth at least considering in pretty much everybody else getting a prescription for antibiotics. The randomized trials included in the two meta-analyses basically included patients receiving 3 days or more of antibiotics. Classes of antibiotics identified in previous work as posing an increased risk of C. difficile–associated diarrhea included the beta-lactams, cephalosporins, fluoroquinolones, and clindamycin – "pretty much everything you prescribe" – Dr. Anderson observed in Estes Park, Colo., at a conference on internal medicine sponsored by the University of Colorado.

"I have to say, if someone comes in with uncomplicated community-acquired pneumonia, I oftentimes don’t prescribe prophylactic probiotics unless they’ve had C. difficile–associated diarrhea before or they’re very fragile. But if something is even a little bit wrong with you, bad diarrheal illness can be the straw that breaks the camel’s back. And I strongly think about prophylactic probiotics in folks on long-term antibiotics, like for a diabetic foot ulcer," he noted.

Dr. Anderson said his typical prescription is for two Lactobacillus acidophilus capsules twice daily.

"The randomized studies done to date don’t let us know the optimal mix of critters or how much is enough," according to the hospitalist.

While preventive probiotic therapy is low cost, Dr. Dominguez noted that a more high-tech therapy for secondary prevention of C. difficile infection is in the developmental pipeline.

A pair of neutralizing, fully human monoclonal antibodies against C. difficile toxins A and B administered together in a single infusion in a randomized, double-blind, placebo-controlled, phase II clinical trial in patients with C. difficile–associated diarrhea didn’t have any effect on duration of hospitalization for that episode. However, it did result in a highly significant 72% reduction in recurrence, according to investigators at Medarex in Princeton, N.J., and the University of Massachusetts, Boston (N. Engl. J. Med. 2010;362:197-205).

"This may be a useful tool in the future for preventing recurrences," Dr. Dominguez commented.

Dr. Dominguez and Dr. Anderson reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

VAIL, COLO. – The strategy of a short course of probiotics prescribed to prevent development of Clostridium difficile–associated diarrhea in patients on antibiotic therapy for any of myriad indications is attracting serious attention in both pediatrics and adult medicine.

Interest in this low-cost and demonstrably low-risk preventive strategy has been driven by a recent favorable meta-analysis by the Cochrane Collaboration.

The Cochrane analysis included all 23 randomized controlled trials of probiotics for the prevention of C. difficile–associated diarrhea in adults or children taking antibiotics. The trials, three of which were conducted in children, included 4,213 subjects, none of whom were immunocompromised, severely ill, or had an underlying gastrointestinal disorder.

The incidence of C. difficile–associated diarrhea was 2.0% in patients randomized to probiotics, compared with 5.5% in controls, for a highly significant 64% reduction in risk. Moreover, the risk of adverse GI events such as abdominal cramping, nausea, fever, taste disturbance, or flatulence was reduced by 20% in the probiotics group (Cochrane Database Syst. Rev. 2013 May 31 [doi: 10.1002/14651858.CD006095.pub3]).

The benefit of prophylactic probiotics was similar in magnitude in children and adults.

"Moderate-quality evidence suggests that probiotics are both safe and effective for preventing C. difficile–associated diarrhea when used along with antibiotics in patients who are not immunocompromised or severely debilitated," the Cochrane investigators concluded.

Neither the current American College of Gastroenterology practice guidelines on C. difficile–associated diarrhea (Am. J. Gastroenterol. 2013;108:478-98) nor the Infectious Diseases Society of America guidelines (Infect. Control Hosp. Epidemiol. 2010;31:431-55) recommend using prophylactic probiotics. However, both guidelines were published before the Cochrane meta-analysis was released, Dr. Samuel R. Dominguez pointed out at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

"Interestingly, a larger effect size was seen in studies of probiotics that contained multiple species compared to a single species, although the data set wasn’t large enough for investigators to be able to look at different specific formulations," added Dr. Dominguez, a pediatric infectious diseases specialist at the University of Colorado, Denver.

He noted that the incidence, severity, and mortality of C. difficile infections have increased dramatically since 2000. Even in children, a population traditionally considered at low risk, a recent population-based study conducted in Olmsted County, Minn., by investigators at the Mayo Clinic concluded that the age- and gender-adjusted incidence of C. difficile infection jumped nearly 13-fold from 1991 to 2009, when it reached 32.6 per 100,000 persons. Three-quarters of the 92 cases were community acquired. Prior studies of C. difficile disease in children may have underestimated the incidence because they were largely based on hospital-acquired cases (Clin. Infect. Dis. 2013;56:1401-6).

Another recent study highlights the serious nature of C. difficile in children, Dr. Dominguez continued. This retrospective cohort study conducted at 41 children’s hospitals included 4,474 patients hospitalized with C. difficile infection and 8,821 matched controls. The in-hospital mortality rate was 1.43% in children with C. difficile infection, compared with 0.66% in controls. In the subgroup of children with hospital-onset C. difficile infection, the mortality risk was an adjusted 6.7-fold higher than in matched controls.

Patients with community-onset C. difficile infection had a mean hospital length of stay that was 5.6 days longer and total hospital costs that were $18,900 greater than those of controls. In patients with hospital-onset C. difficile infection, the differences were even more dramatic: a mean 21.6-day longer length of stay than for controls, and a $93,600 greater hospital cost (Clin. Infect. Dis. 2013;57:1-8).

Dr. Dominguez said that although there is no set policy at Children’s Hospital, his own practice is to recommend probiotics to healthy children who are going to be taking antibiotics.

At a separate conference devoted to adult medicine, Dr. Mel L. Anderson cited both the Cochrane Collaboration meta-analysis and a separate one led by investigators at Toronto’s Hospital for Sick Children that concluded probiotics reduced the incidence of C. difficile–associated diarrhea by 66% (Ann. Intern. Med. 2012;157:878-88).

"If you look at these randomized controlled trials, I think the evidence is fairly convincing. And it’s not an expensive treatment. We use a lot of it in our inpatient service to reduce the risk of antibiotic-associated diarrhea, and C. difficile in particular," said Dr. Anderson, chief of the hospital medicine section at the Denver VA Medical Center.

Prophylactic probiotics are not for the surgical patient who is merely getting a dose or two of perioperative antibiotic coverage. But the preventive therapy is worth at least considering in pretty much everybody else getting a prescription for antibiotics. The randomized trials included in the two meta-analyses basically included patients receiving 3 days or more of antibiotics. Classes of antibiotics identified in previous work as posing an increased risk of C. difficile–associated diarrhea included the beta-lactams, cephalosporins, fluoroquinolones, and clindamycin – "pretty much everything you prescribe" – Dr. Anderson observed in Estes Park, Colo., at a conference on internal medicine sponsored by the University of Colorado.

"I have to say, if someone comes in with uncomplicated community-acquired pneumonia, I oftentimes don’t prescribe prophylactic probiotics unless they’ve had C. difficile–associated diarrhea before or they’re very fragile. But if something is even a little bit wrong with you, bad diarrheal illness can be the straw that breaks the camel’s back. And I strongly think about prophylactic probiotics in folks on long-term antibiotics, like for a diabetic foot ulcer," he noted.

Dr. Anderson said his typical prescription is for two Lactobacillus acidophilus capsules twice daily.

"The randomized studies done to date don’t let us know the optimal mix of critters or how much is enough," according to the hospitalist.

While preventive probiotic therapy is low cost, Dr. Dominguez noted that a more high-tech therapy for secondary prevention of C. difficile infection is in the developmental pipeline.

A pair of neutralizing, fully human monoclonal antibodies against C. difficile toxins A and B administered together in a single infusion in a randomized, double-blind, placebo-controlled, phase II clinical trial in patients with C. difficile–associated diarrhea didn’t have any effect on duration of hospitalization for that episode. However, it did result in a highly significant 72% reduction in recurrence, according to investigators at Medarex in Princeton, N.J., and the University of Massachusetts, Boston (N. Engl. J. Med. 2010;362:197-205).

"This may be a useful tool in the future for preventing recurrences," Dr. Dominguez commented.

Dr. Dominguez and Dr. Anderson reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

VAIL, COLO. – The strategy of a short course of probiotics prescribed to prevent development of Clostridium difficile–associated diarrhea in patients on antibiotic therapy for any of myriad indications is attracting serious attention in both pediatrics and adult medicine.

Interest in this low-cost and demonstrably low-risk preventive strategy has been driven by a recent favorable meta-analysis by the Cochrane Collaboration.

The Cochrane analysis included all 23 randomized controlled trials of probiotics for the prevention of C. difficile–associated diarrhea in adults or children taking antibiotics. The trials, three of which were conducted in children, included 4,213 subjects, none of whom were immunocompromised, severely ill, or had an underlying gastrointestinal disorder.

The incidence of C. difficile–associated diarrhea was 2.0% in patients randomized to probiotics, compared with 5.5% in controls, for a highly significant 64% reduction in risk. Moreover, the risk of adverse GI events such as abdominal cramping, nausea, fever, taste disturbance, or flatulence was reduced by 20% in the probiotics group (Cochrane Database Syst. Rev. 2013 May 31 [doi: 10.1002/14651858.CD006095.pub3]).

The benefit of prophylactic probiotics was similar in magnitude in children and adults.

"Moderate-quality evidence suggests that probiotics are both safe and effective for preventing C. difficile–associated diarrhea when used along with antibiotics in patients who are not immunocompromised or severely debilitated," the Cochrane investigators concluded.

Neither the current American College of Gastroenterology practice guidelines on C. difficile–associated diarrhea (Am. J. Gastroenterol. 2013;108:478-98) nor the Infectious Diseases Society of America guidelines (Infect. Control Hosp. Epidemiol. 2010;31:431-55) recommend using prophylactic probiotics. However, both guidelines were published before the Cochrane meta-analysis was released, Dr. Samuel R. Dominguez pointed out at a conference on pediatric infectious diseases sponsored by the Children’s Hospital Colorado.

"Interestingly, a larger effect size was seen in studies of probiotics that contained multiple species compared to a single species, although the data set wasn’t large enough for investigators to be able to look at different specific formulations," added Dr. Dominguez, a pediatric infectious diseases specialist at the University of Colorado, Denver.

He noted that the incidence, severity, and mortality of C. difficile infections have increased dramatically since 2000. Even in children, a population traditionally considered at low risk, a recent population-based study conducted in Olmsted County, Minn., by investigators at the Mayo Clinic concluded that the age- and gender-adjusted incidence of C. difficile infection jumped nearly 13-fold from 1991 to 2009, when it reached 32.6 per 100,000 persons. Three-quarters of the 92 cases were community acquired. Prior studies of C. difficile disease in children may have underestimated the incidence because they were largely based on hospital-acquired cases (Clin. Infect. Dis. 2013;56:1401-6).

Another recent study highlights the serious nature of C. difficile in children, Dr. Dominguez continued. This retrospective cohort study conducted at 41 children’s hospitals included 4,474 patients hospitalized with C. difficile infection and 8,821 matched controls. The in-hospital mortality rate was 1.43% in children with C. difficile infection, compared with 0.66% in controls. In the subgroup of children with hospital-onset C. difficile infection, the mortality risk was an adjusted 6.7-fold higher than in matched controls.

Patients with community-onset C. difficile infection had a mean hospital length of stay that was 5.6 days longer and total hospital costs that were $18,900 greater than those of controls. In patients with hospital-onset C. difficile infection, the differences were even more dramatic: a mean 21.6-day longer length of stay than for controls, and a $93,600 greater hospital cost (Clin. Infect. Dis. 2013;57:1-8).

Dr. Dominguez said that although there is no set policy at Children’s Hospital, his own practice is to recommend probiotics to healthy children who are going to be taking antibiotics.

At a separate conference devoted to adult medicine, Dr. Mel L. Anderson cited both the Cochrane Collaboration meta-analysis and a separate one led by investigators at Toronto’s Hospital for Sick Children that concluded probiotics reduced the incidence of C. difficile–associated diarrhea by 66% (Ann. Intern. Med. 2012;157:878-88).

"If you look at these randomized controlled trials, I think the evidence is fairly convincing. And it’s not an expensive treatment. We use a lot of it in our inpatient service to reduce the risk of antibiotic-associated diarrhea, and C. difficile in particular," said Dr. Anderson, chief of the hospital medicine section at the Denver VA Medical Center.

Prophylactic probiotics are not for the surgical patient who is merely getting a dose or two of perioperative antibiotic coverage. But the preventive therapy is worth at least considering in pretty much everybody else getting a prescription for antibiotics. The randomized trials included in the two meta-analyses basically included patients receiving 3 days or more of antibiotics. Classes of antibiotics identified in previous work as posing an increased risk of C. difficile–associated diarrhea included the beta-lactams, cephalosporins, fluoroquinolones, and clindamycin – "pretty much everything you prescribe" – Dr. Anderson observed in Estes Park, Colo., at a conference on internal medicine sponsored by the University of Colorado.

"I have to say, if someone comes in with uncomplicated community-acquired pneumonia, I oftentimes don’t prescribe prophylactic probiotics unless they’ve had C. difficile–associated diarrhea before or they’re very fragile. But if something is even a little bit wrong with you, bad diarrheal illness can be the straw that breaks the camel’s back. And I strongly think about prophylactic probiotics in folks on long-term antibiotics, like for a diabetic foot ulcer," he noted.

Dr. Anderson said his typical prescription is for two Lactobacillus acidophilus capsules twice daily.

"The randomized studies done to date don’t let us know the optimal mix of critters or how much is enough," according to the hospitalist.

While preventive probiotic therapy is low cost, Dr. Dominguez noted that a more high-tech therapy for secondary prevention of C. difficile infection is in the developmental pipeline.

A pair of neutralizing, fully human monoclonal antibodies against C. difficile toxins A and B administered together in a single infusion in a randomized, double-blind, placebo-controlled, phase II clinical trial in patients with C. difficile–associated diarrhea didn’t have any effect on duration of hospitalization for that episode. However, it did result in a highly significant 72% reduction in recurrence, according to investigators at Medarex in Princeton, N.J., and the University of Massachusetts, Boston (N. Engl. J. Med. 2010;362:197-205).

"This may be a useful tool in the future for preventing recurrences," Dr. Dominguez commented.

Dr. Dominguez and Dr. Anderson reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

emechcatie@frontlinemedcom.com

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

emechcatie@frontlinemedcom.com

The results of follow-up intestinal biopsies in patients with celiac disease may be useful in evaluating their risk of developing lymphoproliferative malignancies, according to a study that involved more than 7,000 patients in Sweden with celiac disease.

Patients with celiac disease are at an increased risk for lymphoproliferative malignancy (LPM), but the risk was "most pronounced" among those patients whose follow-up biopsy results, obtained after the diagnostic biopsy, had persistent villous atrophy, judging from the study findings. The risk was "less pronounced among those with mucosal healing," reported Dr. Benjamin Lebwohl of the Celiac Disease Center at Columbia University, New York, and his coauthors.

The reason for the increased risk of LPM among patients with celiac disease is not known. These results indicate that the increased risk for LPM "may be affected by mucosal healing," the researchers concluded. The study appears online in Annals of Internal Medicine.

The researchers compared the rates of LPM among 7,625 patients with biopsy-confirmed celiac disease (confirmed by the presence of villous atrophy on the biopsy) and follow-up biopsy to document healing at a median of 1.3 years later. The patients’ median age at the time of diagnosis was 35 years and 63% were female; they were followed for a median of almost 11 years after they were diagnosed and a median of almost 9 years after the follow-up biopsy

Of the total, 53 patients (0.7%) developed LPM a median of 4.9 years after the follow-up biopsy. Persistent villous atrophy was identified in 43% of the follow-up biopsies.

The risk of LPM among those with persistent villous atrophy on the follow-up biopsy was more than twofold greater than the risk among those with biopsies that showed mucosal healing (hazard ratio, 2.26), overall. But during the first year after the follow-up biopsy, the risk of LPM among those with persistent villous atrophy was almost fourfold greater than the risk among those with mucosal healing (HR, 3.67), diminishing over time. The risk was almost twofold higher (HR, 1.99), 1-5 years after the follow-up biopsy and more than 5 years after the biopsy, but was not statically significant.

"It is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said.

Both men and women showed an association between a greater LPM risk and persistent villous atrophy, and the risk was higher among those who were aged older than 60 years at the time of the follow-up biopsy. Those with persistent villous atrophy had a greater risk of developing LPM than that of the general population.

The authors said they were not aware of any study that estimated the hazard ratios for LPM based on the histopathologic results of follow-up biopsies in patients with celiac disease.

One of the limitations of the study was the lack of information on how well patients followed the gluten-free diet, so "it is premature to conclude that the degree of dietary adherence affects LPM risk," the authors said. But their results "should prompt further evaluation of mucosal healing as a goal for patients with celiac disease to reduce their risk for LPM," they concluded.

Patients who not comply with a gluten-free diet are more likely to have persistent villous atrophy, they noted.

Dr. Lebwohl disclosed ties with the National Institutes of Health, the American Scandinavian Foundation, and the Celiac Sprue Association, which funded the study along with Oresbro University Hospital, Karolinska Institutet, the Swedish Society of Medicine, Swedish Research Council, and Swedish Celiac Society. Dr Joseph Murray, a coauthor, received grants from the NIH.

*This story was updated 8/8/2013

emechcatie@frontlinemedcom.com

The Food and Drug Administration has finalized regulations intended to define the term "gluten free" on food packaging in an effort to give celiac disease patients and others following the gluten-free diet confidence that the food they buy is safe for them to consume.

The new regulations, which were nearly a decade in the making, do not require food manufacturers to label products as gluten free. Instead, they lay out the rules to follow if those manufacturers want to voluntarily place "gluten-free" labels on products.

The rules state that manufacturers can label foods "gluten free" if they contain less than 20 parts per million (ppm) of gluten, a protein found in wheat, barley, and rye. According to the FDA, most celiac disease patients can tolerate a small amount of gluten in their food each day.

The regulations prohibit the use of the term "gluten free" on any product that contains wheat, barley, or rye ingredients unless those ingredients have been processed to remove the gluten. Products that are naturally gluten free, such as eggs, fruits, vegetables, and bottled water, also can carry the "gluten free" label.

Physicians who treat celiac disease patients praised the ruling. "Without proper food labeling regulation, celiac patients cannot know what the words ‘gluten free’ mean when they see them on a food label," Dr. Alessio Fasano, medical director of the Center for Celiac Research at MassGeneral Hospital for Children, Boston, said in a statement.

About 3 million people in the United States have celiac disease; many of them are undiagnosed. The regulatory action brings the United States into line with Canada and the European Union, both of which consider "gluten free" to mean less than 20 ppm of gluten.

Manufacturers have1 year to comply with the regulations or risk facing compliance action from the FDA. The agency said that the vast majority of "gluten free"–labeled products on the shelves today – 95% – already comply with the regulations.

The Food and Drug Administration has finalized regulations intended to define the term "gluten free" on food packaging in an effort to give celiac disease patients and others following the gluten-free diet confidence that the food they buy is safe for them to consume.

The new regulations, which were nearly a decade in the making, do not require food manufacturers to label products as gluten free. Instead, they lay out the rules to follow if those manufacturers want to voluntarily place "gluten-free" labels on products.

The rules state that manufacturers can label foods "gluten free" if they contain less than 20 parts per million (ppm) of gluten, a protein found in wheat, barley, and rye. According to the FDA, most celiac disease patients can tolerate a small amount of gluten in their food each day.

The regulations prohibit the use of the term "gluten free" on any product that contains wheat, barley, or rye ingredients unless those ingredients have been processed to remove the gluten. Products that are naturally gluten free, such as eggs, fruits, vegetables, and bottled water, also can carry the "gluten free" label.

Physicians who treat celiac disease patients praised the ruling. "Without proper food labeling regulation, celiac patients cannot know what the words ‘gluten free’ mean when they see them on a food label," Dr. Alessio Fasano, medical director of the Center for Celiac Research at MassGeneral Hospital for Children, Boston, said in a statement.

About 3 million people in the United States have celiac disease; many of them are undiagnosed. The regulatory action brings the United States into line with Canada and the European Union, both of which consider "gluten free" to mean less than 20 ppm of gluten.

Manufacturers have1 year to comply with the regulations or risk facing compliance action from the FDA. The agency said that the vast majority of "gluten free"–labeled products on the shelves today – 95% – already comply with the regulations.

The Food and Drug Administration has finalized regulations intended to define the term "gluten free" on food packaging in an effort to give celiac disease patients and others following the gluten-free diet confidence that the food they buy is safe for them to consume.

The new regulations, which were nearly a decade in the making, do not require food manufacturers to label products as gluten free. Instead, they lay out the rules to follow if those manufacturers want to voluntarily place "gluten-free" labels on products.

The rules state that manufacturers can label foods "gluten free" if they contain less than 20 parts per million (ppm) of gluten, a protein found in wheat, barley, and rye. According to the FDA, most celiac disease patients can tolerate a small amount of gluten in their food each day.

The regulations prohibit the use of the term "gluten free" on any product that contains wheat, barley, or rye ingredients unless those ingredients have been processed to remove the gluten. Products that are naturally gluten free, such as eggs, fruits, vegetables, and bottled water, also can carry the "gluten free" label.

Physicians who treat celiac disease patients praised the ruling. "Without proper food labeling regulation, celiac patients cannot know what the words ‘gluten free’ mean when they see them on a food label," Dr. Alessio Fasano, medical director of the Center for Celiac Research at MassGeneral Hospital for Children, Boston, said in a statement.

About 3 million people in the United States have celiac disease; many of them are undiagnosed. The regulatory action brings the United States into line with Canada and the European Union, both of which consider "gluten free" to mean less than 20 ppm of gluten.

Manufacturers have1 year to comply with the regulations or risk facing compliance action from the FDA. The agency said that the vast majority of "gluten free"–labeled products on the shelves today – 95% – already comply with the regulations.

Patients with watery diarrhea that does not resolve over several days should be tested specifically for Cyclospora infection, according to Dr. Tom Frieden, director of the Centers for Disease Control and Prevention.

The CDC is investigating an outbreak of Cyclospora infections in conjunction with federal and local partners, including the Food and Drug Administration. The first lab-confirmed cases reported to the CDC were in Iowa in two people who had not traveled internationally for 14 days before the onset of the illness.

Centers for Disease Control and Prevention

As of July 24, the CDC had been notified of 285 cases of Cyclospora infection in multiple states, including Iowa, Nebraska, Texas, Wisconsin, Georgia, Minnesota, Connecticut, New Jersey, and Ohio, Dr. Frieden said during a CDC telebriefing on July 25. Additionally, single cases were reported in both Illinois and Kansas that may have been acquired in another state.

Most patients became ill in June or early July, and it is too soon to say whether the outbreak is ongoing or subsiding, he said. "We have not yet identified a source, although I am confident we will," he added.

Infection with the parasite Cyclospora cayetanensis typically causes watery diarrhea. "People who have illness that hasn’t gone away on its own in several days should see their health care provider, and discuss the possibility of Cyclospora," he said. Testing of stool samples for Cyclospora "should be specifically requested in people who’ve had diarrheal illness that hasn’t gone away in several days."

While the cause of the current outbreak has not yet been identified, Dr. Frieden said that the best way to prevent infection is to avoid food or water that may have been contaminated with the parasite and to carefully wash fresh produce before eating.

Cyclospora can stick to some foods, though, so washing produce can be helpful but does not eliminate the risk, he noted.

emechcatie@frontlinemedcom.com

Patients with watery diarrhea that does not resolve over several days should be tested specifically for Cyclospora infection, according to Dr. Tom Frieden, director of the Centers for Disease Control and Prevention.

The CDC is investigating an outbreak of Cyclospora infections in conjunction with federal and local partners, including the Food and Drug Administration. The first lab-confirmed cases reported to the CDC were in Iowa in two people who had not traveled internationally for 14 days before the onset of the illness.

Centers for Disease Control and Prevention

As of July 24, the CDC had been notified of 285 cases of Cyclospora infection in multiple states, including Iowa, Nebraska, Texas, Wisconsin, Georgia, Minnesota, Connecticut, New Jersey, and Ohio, Dr. Frieden said during a CDC telebriefing on July 25. Additionally, single cases were reported in both Illinois and Kansas that may have been acquired in another state.

Most patients became ill in June or early July, and it is too soon to say whether the outbreak is ongoing or subsiding, he said. "We have not yet identified a source, although I am confident we will," he added.

Infection with the parasite Cyclospora cayetanensis typically causes watery diarrhea. "People who have illness that hasn’t gone away on its own in several days should see their health care provider, and discuss the possibility of Cyclospora," he said. Testing of stool samples for Cyclospora "should be specifically requested in people who’ve had diarrheal illness that hasn’t gone away in several days."

While the cause of the current outbreak has not yet been identified, Dr. Frieden said that the best way to prevent infection is to avoid food or water that may have been contaminated with the parasite and to carefully wash fresh produce before eating.

Cyclospora can stick to some foods, though, so washing produce can be helpful but does not eliminate the risk, he noted.

emechcatie@frontlinemedcom.com

Patients with watery diarrhea that does not resolve over several days should be tested specifically for Cyclospora infection, according to Dr. Tom Frieden, director of the Centers for Disease Control and Prevention.

The CDC is investigating an outbreak of Cyclospora infections in conjunction with federal and local partners, including the Food and Drug Administration. The first lab-confirmed cases reported to the CDC were in Iowa in two people who had not traveled internationally for 14 days before the onset of the illness.

Centers for Disease Control and Prevention

As of July 24, the CDC had been notified of 285 cases of Cyclospora infection in multiple states, including Iowa, Nebraska, Texas, Wisconsin, Georgia, Minnesota, Connecticut, New Jersey, and Ohio, Dr. Frieden said during a CDC telebriefing on July 25. Additionally, single cases were reported in both Illinois and Kansas that may have been acquired in another state.

Most patients became ill in June or early July, and it is too soon to say whether the outbreak is ongoing or subsiding, he said. "We have not yet identified a source, although I am confident we will," he added.

Infection with the parasite Cyclospora cayetanensis typically causes watery diarrhea. "People who have illness that hasn’t gone away on its own in several days should see their health care provider, and discuss the possibility of Cyclospora," he said. Testing of stool samples for Cyclospora "should be specifically requested in people who’ve had diarrheal illness that hasn’t gone away in several days."

While the cause of the current outbreak has not yet been identified, Dr. Frieden said that the best way to prevent infection is to avoid food or water that may have been contaminated with the parasite and to carefully wash fresh produce before eating.

Cyclospora can stick to some foods, though, so washing produce can be helpful but does not eliminate the risk, he noted.

emechcatie@frontlinemedcom.com

Olmesartan can cause intestinal symptoms severe enough to warrant hospitalization, even years after initiating treatment with the antihypertensive drug, the Food and Drug Administration announced July 3.

In a Drug Safety Communication, the agency warns that spruelike enteropathy – with symptoms that can include severe, chronic diarrhea with significant weight loss, sometimes requiring hospitalization – has been associated with olmesartan use, months to years after starting treatment. "If patients taking olmesartan develop these symptoms and no other cause is found, the drug should be discontinued and therapy with another antihypertensive started," the statement says. Celiac disease is one of the possible causes of such symptoms that the FDA recommends should be investigated.

Spruelike enteropathy symptoms improved in all patients after they stopped taking the drug, the statement adds.

This information is being added to the olmesartan label, which currently lists diarrhea as a side effect of the drug. Olmesartan, approved in 2002 for the treatment of hypertension, is an angiotensin II receptor blocker (ARB) marketed as Benicar, Benicar HCT, Azor, and Tribenzor. The drug also is available in generic formulations. Spruelike enteropathy has not been reported with other ARBs, according to the FDA.

The warning is based on the agency’s evaluation of data that "found clear evidence of an association between olmesartan and spruelike enteropathy," the statement says. The data include the following:

• A total of 23 cases of patients reported to the FDA’s Adverse Event Reporting System, who presented with late-onset diarrhea and significant weight loss; in some patients, biopsies that showed intestinal villous atrophy. All patients improved after the drug was stopped, but 10 developed symptoms again when treatment resumed.

• A published case series of spruelike enteropathy associated with olmesartan in 22 patients, with symptoms that were similar to the cases reported to the FDA, as well as evidence of villous atrophy. These patients also improved after the drug was stopped, and in 18 patients, follow-up intestinal biopsies documented recovery or improvement of the duodenum after treatment was stopped (Mayo Clin. Proc. 2012;87:732-8).

• An analysis of claims and administrative data that identified a higher rate of celiac disease diagnoses among patients on olmesartan compared with those on other ARBs.

The mechanism for the enteropathy is "uncertain" but, based on currently available information, could be a localized, delayed hypersensitivity or cell-mediated immune response, the statement said.

In 2012, about 10.6 million prescriptions for olmesartan products were dispensed to about 1.9 million patients in U.S. outpatient retail pharmacies, according to the FDA.

Adverse events associated with olmesartan and olmesartan-containing products should be reported to the FDA’s Adverse Event Reporting System at 800-332-1088 or www.fda.gov/medwatch/.

emechcatie@frontlinemedcom.com

Olmesartan can cause intestinal symptoms severe enough to warrant hospitalization, even years after initiating treatment with the antihypertensive drug, the Food and Drug Administration announced July 3.

In a Drug Safety Communication, the agency warns that spruelike enteropathy – with symptoms that can include severe, chronic diarrhea with significant weight loss, sometimes requiring hospitalization – has been associated with olmesartan use, months to years after starting treatment. "If patients taking olmesartan develop these symptoms and no other cause is found, the drug should be discontinued and therapy with another antihypertensive started," the statement says. Celiac disease is one of the possible causes of such symptoms that the FDA recommends should be investigated.

Spruelike enteropathy symptoms improved in all patients after they stopped taking the drug, the statement adds.

This information is being added to the olmesartan label, which currently lists diarrhea as a side effect of the drug. Olmesartan, approved in 2002 for the treatment of hypertension, is an angiotensin II receptor blocker (ARB) marketed as Benicar, Benicar HCT, Azor, and Tribenzor. The drug also is available in generic formulations. Spruelike enteropathy has not been reported with other ARBs, according to the FDA.

The warning is based on the agency’s evaluation of data that "found clear evidence of an association between olmesartan and spruelike enteropathy," the statement says. The data include the following:

• A total of 23 cases of patients reported to the FDA’s Adverse Event Reporting System, who presented with late-onset diarrhea and significant weight loss; in some patients, biopsies that showed intestinal villous atrophy. All patients improved after the drug was stopped, but 10 developed symptoms again when treatment resumed.

• A published case series of spruelike enteropathy associated with olmesartan in 22 patients, with symptoms that were similar to the cases reported to the FDA, as well as evidence of villous atrophy. These patients also improved after the drug was stopped, and in 18 patients, follow-up intestinal biopsies documented recovery or improvement of the duodenum after treatment was stopped (Mayo Clin. Proc. 2012;87:732-8).

• An analysis of claims and administrative data that identified a higher rate of celiac disease diagnoses among patients on olmesartan compared with those on other ARBs.

The mechanism for the enteropathy is "uncertain" but, based on currently available information, could be a localized, delayed hypersensitivity or cell-mediated immune response, the statement said.

In 2012, about 10.6 million prescriptions for olmesartan products were dispensed to about 1.9 million patients in U.S. outpatient retail pharmacies, according to the FDA.

Adverse events associated with olmesartan and olmesartan-containing products should be reported to the FDA’s Adverse Event Reporting System at 800-332-1088 or www.fda.gov/medwatch/.

emechcatie@frontlinemedcom.com

Olmesartan can cause intestinal symptoms severe enough to warrant hospitalization, even years after initiating treatment with the antihypertensive drug, the Food and Drug Administration announced July 3.

In a Drug Safety Communication, the agency warns that spruelike enteropathy – with symptoms that can include severe, chronic diarrhea with significant weight loss, sometimes requiring hospitalization – has been associated with olmesartan use, months to years after starting treatment. "If patients taking olmesartan develop these symptoms and no other cause is found, the drug should be discontinued and therapy with another antihypertensive started," the statement says. Celiac disease is one of the possible causes of such symptoms that the FDA recommends should be investigated.

Spruelike enteropathy symptoms improved in all patients after they stopped taking the drug, the statement adds.

This information is being added to the olmesartan label, which currently lists diarrhea as a side effect of the drug. Olmesartan, approved in 2002 for the treatment of hypertension, is an angiotensin II receptor blocker (ARB) marketed as Benicar, Benicar HCT, Azor, and Tribenzor. The drug also is available in generic formulations. Spruelike enteropathy has not been reported with other ARBs, according to the FDA.

The warning is based on the agency’s evaluation of data that "found clear evidence of an association between olmesartan and spruelike enteropathy," the statement says. The data include the following:

• A total of 23 cases of patients reported to the FDA’s Adverse Event Reporting System, who presented with late-onset diarrhea and significant weight loss; in some patients, biopsies that showed intestinal villous atrophy. All patients improved after the drug was stopped, but 10 developed symptoms again when treatment resumed.

• A published case series of spruelike enteropathy associated with olmesartan in 22 patients, with symptoms that were similar to the cases reported to the FDA, as well as evidence of villous atrophy. These patients also improved after the drug was stopped, and in 18 patients, follow-up intestinal biopsies documented recovery or improvement of the duodenum after treatment was stopped (Mayo Clin. Proc. 2012;87:732-8).

• An analysis of claims and administrative data that identified a higher rate of celiac disease diagnoses among patients on olmesartan compared with those on other ARBs.

The mechanism for the enteropathy is "uncertain" but, based on currently available information, could be a localized, delayed hypersensitivity or cell-mediated immune response, the statement said.

In 2012, about 10.6 million prescriptions for olmesartan products were dispensed to about 1.9 million patients in U.S. outpatient retail pharmacies, according to the FDA.

Adverse events associated with olmesartan and olmesartan-containing products should be reported to the FDA’s Adverse Event Reporting System at 800-332-1088 or www.fda.gov/medwatch/.

emechcatie@frontlinemedcom.com

In what they called the first comparative epidemiologic study of inflammatory bowel disease across the region, researchers calculated an incidence of 1.37 cases/100,000 people in Asia, and 23.67 cases/100,000 people in Australia.

And despite the fact that these rates are dwarfed by Western nations, "these figures still represent a clinically important disease burden, considering that 20 years ago, IBD [inflammatory bowel disease] was rare or almost nonexistent in Asia," wrote Siew C. Ng, Ph.D., in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2013.04.007).

Source: American Gastroenterological Association

In the report Dr. Ng of the Chinese University of Hong Kong, and her colleagues looked at data from the Asia-Pacific Crohn’s and Colitis Epidemiology (ACCESS) study.

That database included information from 21 centers in 12 cities in nine countries, including China, Australia, Hong Kong, and Thailand.

Specifically, the researchers focused on incident IBD cases diagnosed between April 1, 2011, and March 31, 2012, all of which were confirmed clinically as well as endoscopically, histologically, and radiographically.

The researchers found that during the 1-year period, there were 419 new IBD cases, including 232 (55.4%) classified as ulcerative colitis (UC), 166 (39.6%) as Crohn’s disease (CD), and 21 (5.0%) undetermined.

That translated to a crude annual overall incidence of IBD of 1.37/100,000 people (95% CI: 1.25-1.51) in Asia, and 23.67 (95% CI: 18.46-29.85) in Australia.

The authors then looked at individual patient demographics.

Overall, the mean age at the time of diagnosis was 39 years, with a median number of months from symptom onset to diagnosis of 5 months in Asia and 6 months in Australia.

They also found that while inflammatory disease phenotype was reported in 66% of patients in Asia, it was found in 88% of Australian patients (P = .005).

Indeed, 3% of patients in Asia reported a family history of IBD, compared with 17% of patients in Australia (P less than 0.001).

Severity of disease was also catalogued. Penetrating disease characterized 19% and 2% of cases in Asia and Australia, respectively (P = .012).

Meanwhile, stricturing disease was diagnosed in 17% of Asian cases and 10% of Australian cases (P = .277), and perianal disease in 18% and 12% of Asians and Australians, respectively (P = .356).

Finally, the researchers looked at treatment patterns between Asia and Australia, and found that while use of antibiotics, immunosuppressives, and biologic therapy were similar, mesalazine (79% vs. 62%; P less than .012) and corticosteroids (62% vs. 28%; P less than .0001) were more commonly prescribed in Australia than in Asia.

According to Dr. Ng, in a region that is host to more than 4.2 billion people, "The emerging incidence in Asia offers a unique opportunity to study etiologic factors, particularly factors associated with Western lifestyle, including improved home amenities, refrigeration, consumption of protein- and carbohydrate-rich diets, widespread use of antibiotics, vaccination, and industrial pollution."

She added: "The complex disease behavior for CD in Asia has major implications for local health care planning and resource allocation."

The authors disclosed no conflicts of interest. The study was supported by Ferring Pharmaceuticals, maker of mesalazine, which is used in IBD.

In what they called the first comparative epidemiologic study of inflammatory bowel disease across the region, researchers calculated an incidence of 1.37 cases/100,000 people in Asia, and 23.67 cases/100,000 people in Australia.

And despite the fact that these rates are dwarfed by Western nations, "these figures still represent a clinically important disease burden, considering that 20 years ago, IBD [inflammatory bowel disease] was rare or almost nonexistent in Asia," wrote Siew C. Ng, Ph.D., in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2013.04.007).

Source: American Gastroenterological Association

In the report Dr. Ng of the Chinese University of Hong Kong, and her colleagues looked at data from the Asia-Pacific Crohn’s and Colitis Epidemiology (ACCESS) study.

That database included information from 21 centers in 12 cities in nine countries, including China, Australia, Hong Kong, and Thailand.

Specifically, the researchers focused on incident IBD cases diagnosed between April 1, 2011, and March 31, 2012, all of which were confirmed clinically as well as endoscopically, histologically, and radiographically.

The researchers found that during the 1-year period, there were 419 new IBD cases, including 232 (55.4%) classified as ulcerative colitis (UC), 166 (39.6%) as Crohn’s disease (CD), and 21 (5.0%) undetermined.

That translated to a crude annual overall incidence of IBD of 1.37/100,000 people (95% CI: 1.25-1.51) in Asia, and 23.67 (95% CI: 18.46-29.85) in Australia.

The authors then looked at individual patient demographics.

Overall, the mean age at the time of diagnosis was 39 years, with a median number of months from symptom onset to diagnosis of 5 months in Asia and 6 months in Australia.

They also found that while inflammatory disease phenotype was reported in 66% of patients in Asia, it was found in 88% of Australian patients (P = .005).

Indeed, 3% of patients in Asia reported a family history of IBD, compared with 17% of patients in Australia (P less than 0.001).

Severity of disease was also catalogued. Penetrating disease characterized 19% and 2% of cases in Asia and Australia, respectively (P = .012).

Meanwhile, stricturing disease was diagnosed in 17% of Asian cases and 10% of Australian cases (P = .277), and perianal disease in 18% and 12% of Asians and Australians, respectively (P = .356).

Finally, the researchers looked at treatment patterns between Asia and Australia, and found that while use of antibiotics, immunosuppressives, and biologic therapy were similar, mesalazine (79% vs. 62%; P less than .012) and corticosteroids (62% vs. 28%; P less than .0001) were more commonly prescribed in Australia than in Asia.

According to Dr. Ng, in a region that is host to more than 4.2 billion people, "The emerging incidence in Asia offers a unique opportunity to study etiologic factors, particularly factors associated with Western lifestyle, including improved home amenities, refrigeration, consumption of protein- and carbohydrate-rich diets, widespread use of antibiotics, vaccination, and industrial pollution."

She added: "The complex disease behavior for CD in Asia has major implications for local health care planning and resource allocation."

The authors disclosed no conflicts of interest. The study was supported by Ferring Pharmaceuticals, maker of mesalazine, which is used in IBD.

In what they called the first comparative epidemiologic study of inflammatory bowel disease across the region, researchers calculated an incidence of 1.37 cases/100,000 people in Asia, and 23.67 cases/100,000 people in Australia.

And despite the fact that these rates are dwarfed by Western nations, "these figures still represent a clinically important disease burden, considering that 20 years ago, IBD [inflammatory bowel disease] was rare or almost nonexistent in Asia," wrote Siew C. Ng, Ph.D., in the July issue of Gastroenterology (doi: 10.1053/j.gastro.2013.04.007).

Source: American Gastroenterological Association

In the report Dr. Ng of the Chinese University of Hong Kong, and her colleagues looked at data from the Asia-Pacific Crohn’s and Colitis Epidemiology (ACCESS) study.

That database included information from 21 centers in 12 cities in nine countries, including China, Australia, Hong Kong, and Thailand.

Specifically, the researchers focused on incident IBD cases diagnosed between April 1, 2011, and March 31, 2012, all of which were confirmed clinically as well as endoscopically, histologically, and radiographically.

The researchers found that during the 1-year period, there were 419 new IBD cases, including 232 (55.4%) classified as ulcerative colitis (UC), 166 (39.6%) as Crohn’s disease (CD), and 21 (5.0%) undetermined.

That translated to a crude annual overall incidence of IBD of 1.37/100,000 people (95% CI: 1.25-1.51) in Asia, and 23.67 (95% CI: 18.46-29.85) in Australia.

The authors then looked at individual patient demographics.

Overall, the mean age at the time of diagnosis was 39 years, with a median number of months from symptom onset to diagnosis of 5 months in Asia and 6 months in Australia.

They also found that while inflammatory disease phenotype was reported in 66% of patients in Asia, it was found in 88% of Australian patients (P = .005).

Indeed, 3% of patients in Asia reported a family history of IBD, compared with 17% of patients in Australia (P less than 0.001).

Severity of disease was also catalogued. Penetrating disease characterized 19% and 2% of cases in Asia and Australia, respectively (P = .012).

Meanwhile, stricturing disease was diagnosed in 17% of Asian cases and 10% of Australian cases (P = .277), and perianal disease in 18% and 12% of Asians and Australians, respectively (P = .356).

Finally, the researchers looked at treatment patterns between Asia and Australia, and found that while use of antibiotics, immunosuppressives, and biologic therapy were similar, mesalazine (79% vs. 62%; P less than .012) and corticosteroids (62% vs. 28%; P less than .0001) were more commonly prescribed in Australia than in Asia.

According to Dr. Ng, in a region that is host to more than 4.2 billion people, "The emerging incidence in Asia offers a unique opportunity to study etiologic factors, particularly factors associated with Western lifestyle, including improved home amenities, refrigeration, consumption of protein- and carbohydrate-rich diets, widespread use of antibiotics, vaccination, and industrial pollution."

She added: "The complex disease behavior for CD in Asia has major implications for local health care planning and resource allocation."

The authors disclosed no conflicts of interest. The study was supported by Ferring Pharmaceuticals, maker of mesalazine, which is used in IBD.