IBD & Intestinal Disorders

Vedolizumab was not superior to placebo for inducing remission at 6 weeks in patients with Crohn’s disease who failed to respond to anti–tumor necrosis factor therapy, according to findings from the double-blind, phase III GEMINI 3 trial.

However, therapeutic benefit from the humanized, anti–alpha-4 beta-7 integrin, immunoglobulin G1 monoclonal antibody did become apparent by week 10, Dr. Bruce E. Sands of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues report in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2014.05.008).

Source: American Gastroenterological Association

The investigators randomized 315 patients with moderately to severely active Crohn’s disease who failed anti-TNF therapy to receive 300 mg of vedolizumab (158 patients) or placebo (157 patients) intravenously at weeks 0, 2, and 6. The results showed that 15.2% of the vedolizumab group was in remission at week 6, compared with 12.1% of the placebo group (relative risk, 1.2). At week 10, 26.6% of patients in the vedolizumab group, compared with 12.1% of those in the placebo group, were in remission (RR, 2.2), the investigators reported.

More patients in the vedolizumab group did, however, achieve at least a 100-point decrease in the Crohn’s Disease Activity Index (CDAI) score at both 6 weeks (39.2% vs. 22.3% of placebo patients; RR, 1.8) and 10 weeks (46.8% vs. 24.8%; RR, 1.4), they said.

The incidence and type of adverse events were similar in both groups.

GEMINI 3 was conducted between November 2010 and April 2012 at 107 sites in North America, Europe, Asia, Africa, and Australia. Participants were aged 18-80 years with moderately to severely active Crohn’s disease (defined in part by a CDAI score of 220-400 points), with known involvement of the ileum and/or colon at 3 or more months before enrollment.

Remission was defined by a CDAI score of 150 points or less.

Treatment with TNF antagonists has improved the care of patients with Crohn’s disease that is refractory to other treatments, but in controlled trials anti-TNF therapy failed in about two-thirds of patients. Treatment is also associated with an increased risk of serious infections in some patients. Natalizumab, another treatment used in Crohn’s disease, has been limited by its association with an increased risk of progressive multifocal leukoencephalopathy.

"Because of these limitations with TNF antagonists and natalizumab, therapies for patients with TNF antagonist failure are needed, and those that selectively inhibit lymphocyte trafficking to the gut may yield important safety benefits," the investigators said.

Vedolizumab was shown in the pivotal GEMINI 2 study to be safe and effective for induction and maintenance in patients with moderately to severely active Crohn’s disease who failed one or more prior therapies; GEMINI 3 specifically focuses on patients with prior TNF antagonist failure.

"The results of this short-term study support the safety of vedolizumab in patients with Crohn’s disease and are consistent with the drug’s postulated gut-selective mechanism of action," the investigators said.

Furthermore, several prespecified outcomes suggest that in addition to leading to clinical remission in the TNF antagonist–naive patients with Crohn’s disease, vedolizumab may lead to clinical remission at 10 weeks in those who failed TNF antagonist therapy.

"These clinically relevant response kinetics have potential implications for bridging induction therapy to vedolizumab maintenance therapy, which has established efficacy, in patients with this lifelong condition," they concluded.

This study was funded by Millennium Pharmaceuticals (doing business as Takeda Pharmaceuticals). Dr. Sands reported receiving consulting and advisory board fees, as well as clinical research/institutional grant support from AbbVie, Janssen, and Takeda. Detailed disclosures for all authors are available with the full text of the article.

Vedolizumab was not superior to placebo for inducing remission at 6 weeks in patients with Crohn’s disease who failed to respond to anti–tumor necrosis factor therapy, according to findings from the double-blind, phase III GEMINI 3 trial.

However, therapeutic benefit from the humanized, anti–alpha-4 beta-7 integrin, immunoglobulin G1 monoclonal antibody did become apparent by week 10, Dr. Bruce E. Sands of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues report in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2014.05.008).

Source: American Gastroenterological Association

The investigators randomized 315 patients with moderately to severely active Crohn’s disease who failed anti-TNF therapy to receive 300 mg of vedolizumab (158 patients) or placebo (157 patients) intravenously at weeks 0, 2, and 6. The results showed that 15.2% of the vedolizumab group was in remission at week 6, compared with 12.1% of the placebo group (relative risk, 1.2). At week 10, 26.6% of patients in the vedolizumab group, compared with 12.1% of those in the placebo group, were in remission (RR, 2.2), the investigators reported.

More patients in the vedolizumab group did, however, achieve at least a 100-point decrease in the Crohn’s Disease Activity Index (CDAI) score at both 6 weeks (39.2% vs. 22.3% of placebo patients; RR, 1.8) and 10 weeks (46.8% vs. 24.8%; RR, 1.4), they said.

The incidence and type of adverse events were similar in both groups.

GEMINI 3 was conducted between November 2010 and April 2012 at 107 sites in North America, Europe, Asia, Africa, and Australia. Participants were aged 18-80 years with moderately to severely active Crohn’s disease (defined in part by a CDAI score of 220-400 points), with known involvement of the ileum and/or colon at 3 or more months before enrollment.

Remission was defined by a CDAI score of 150 points or less.

Treatment with TNF antagonists has improved the care of patients with Crohn’s disease that is refractory to other treatments, but in controlled trials anti-TNF therapy failed in about two-thirds of patients. Treatment is also associated with an increased risk of serious infections in some patients. Natalizumab, another treatment used in Crohn’s disease, has been limited by its association with an increased risk of progressive multifocal leukoencephalopathy.

"Because of these limitations with TNF antagonists and natalizumab, therapies for patients with TNF antagonist failure are needed, and those that selectively inhibit lymphocyte trafficking to the gut may yield important safety benefits," the investigators said.

Vedolizumab was shown in the pivotal GEMINI 2 study to be safe and effective for induction and maintenance in patients with moderately to severely active Crohn’s disease who failed one or more prior therapies; GEMINI 3 specifically focuses on patients with prior TNF antagonist failure.

"The results of this short-term study support the safety of vedolizumab in patients with Crohn’s disease and are consistent with the drug’s postulated gut-selective mechanism of action," the investigators said.

Furthermore, several prespecified outcomes suggest that in addition to leading to clinical remission in the TNF antagonist–naive patients with Crohn’s disease, vedolizumab may lead to clinical remission at 10 weeks in those who failed TNF antagonist therapy.

"These clinically relevant response kinetics have potential implications for bridging induction therapy to vedolizumab maintenance therapy, which has established efficacy, in patients with this lifelong condition," they concluded.

This study was funded by Millennium Pharmaceuticals (doing business as Takeda Pharmaceuticals). Dr. Sands reported receiving consulting and advisory board fees, as well as clinical research/institutional grant support from AbbVie, Janssen, and Takeda. Detailed disclosures for all authors are available with the full text of the article.

Vedolizumab was not superior to placebo for inducing remission at 6 weeks in patients with Crohn’s disease who failed to respond to anti–tumor necrosis factor therapy, according to findings from the double-blind, phase III GEMINI 3 trial.

However, therapeutic benefit from the humanized, anti–alpha-4 beta-7 integrin, immunoglobulin G1 monoclonal antibody did become apparent by week 10, Dr. Bruce E. Sands of the Icahn School of Medicine at Mount Sinai, New York, and his colleagues report in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2014.05.008).

Source: American Gastroenterological Association

The investigators randomized 315 patients with moderately to severely active Crohn’s disease who failed anti-TNF therapy to receive 300 mg of vedolizumab (158 patients) or placebo (157 patients) intravenously at weeks 0, 2, and 6. The results showed that 15.2% of the vedolizumab group was in remission at week 6, compared with 12.1% of the placebo group (relative risk, 1.2). At week 10, 26.6% of patients in the vedolizumab group, compared with 12.1% of those in the placebo group, were in remission (RR, 2.2), the investigators reported.

More patients in the vedolizumab group did, however, achieve at least a 100-point decrease in the Crohn’s Disease Activity Index (CDAI) score at both 6 weeks (39.2% vs. 22.3% of placebo patients; RR, 1.8) and 10 weeks (46.8% vs. 24.8%; RR, 1.4), they said.

The incidence and type of adverse events were similar in both groups.

GEMINI 3 was conducted between November 2010 and April 2012 at 107 sites in North America, Europe, Asia, Africa, and Australia. Participants were aged 18-80 years with moderately to severely active Crohn’s disease (defined in part by a CDAI score of 220-400 points), with known involvement of the ileum and/or colon at 3 or more months before enrollment.

Remission was defined by a CDAI score of 150 points or less.

Treatment with TNF antagonists has improved the care of patients with Crohn’s disease that is refractory to other treatments, but in controlled trials anti-TNF therapy failed in about two-thirds of patients. Treatment is also associated with an increased risk of serious infections in some patients. Natalizumab, another treatment used in Crohn’s disease, has been limited by its association with an increased risk of progressive multifocal leukoencephalopathy.

"Because of these limitations with TNF antagonists and natalizumab, therapies for patients with TNF antagonist failure are needed, and those that selectively inhibit lymphocyte trafficking to the gut may yield important safety benefits," the investigators said.

Vedolizumab was shown in the pivotal GEMINI 2 study to be safe and effective for induction and maintenance in patients with moderately to severely active Crohn’s disease who failed one or more prior therapies; GEMINI 3 specifically focuses on patients with prior TNF antagonist failure.

"The results of this short-term study support the safety of vedolizumab in patients with Crohn’s disease and are consistent with the drug’s postulated gut-selective mechanism of action," the investigators said.

Furthermore, several prespecified outcomes suggest that in addition to leading to clinical remission in the TNF antagonist–naive patients with Crohn’s disease, vedolizumab may lead to clinical remission at 10 weeks in those who failed TNF antagonist therapy.

"These clinically relevant response kinetics have potential implications for bridging induction therapy to vedolizumab maintenance therapy, which has established efficacy, in patients with this lifelong condition," they concluded.

This study was funded by Millennium Pharmaceuticals (doing business as Takeda Pharmaceuticals). Dr. Sands reported receiving consulting and advisory board fees, as well as clinical research/institutional grant support from AbbVie, Janssen, and Takeda. Detailed disclosures for all authors are available with the full text of the article.

The risk of lymphoma is no greater in children with inflammatory bowel disease who are treated with anti–tumor necrosis factor therapy than in adults treated with anti-TNF therapies or in children treated with other therapies for IBD, according to findings from a systematic review.

The review, which included 65 studies involving a total of 5,528 patients with 9,516 patient-years of follow-up, also showed that the rate of serious infection was lower among children with IBD who were treated with anti-TNF agents than among those treated with steroids or among adults treated with anti-TNF agents, Dr. Parambir S. Dulai of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2014.01.021).

Source: American Gastroenterological Association

Two patients developed lymphoma, for a rate of 2.1/10,000 patient-years of follow-up (PYF), which did not differ significantly from the expected rate among children (5.8/100,000 PYF), the rate among pediatric patients receiving thiopurine monotherapy (4.5/10,000), or the rate among adults treated with anti-TNF agents (6.1/10,000), the investigators found.

The rate of serious infections was 352/10,000 PYF in pediatric patients treated with anti-TNF agents as part of prospective studies included in the review, which was similar to the expected rate in those treated with immunomodulator therapy (333/10,000 PYF), and significantly lower than the expected rate in those treated with glucocorticoids (730/10,000 PYF) and adults treated with anti-TNF agents (654/10,000 PYF).

Of seven deaths that occurred among the patients, five were considered related to treatment (four cases of sepsis, one case of arrhythmia), for a rate of 5.3/10,000 PYF.

Although anti-TNF therapy is an effective treatment option for pediatric IBD, many physicians are hesitant about prescribing anti-TNFs to children because of concerns about infection and lymphoma risk based on the adult literature and case reports of hepatosplenic T-cell lymphoma. However, the findings of this pooled analysis suggest that such concerns may be unfounded.

Older age, sex, and duration of IBD have been linked with increased risk of lymphoproliferative disorders and could help explain the observed differences between adults and pediatric IBD patients with respect to lymphoma rates after anti-TNF exposure, the investigators said.

"Overall, the risk of serious infection, lymphoma, and death with anti-TNF therapy in pediatric IBD is very low," they wrote.

However, they noted that the study is limited by a number of factors, including short duration of per-person follow-up, which means that while the data are promising, they are "not definitive in answering the question of whether anti-TNF therapy is associated with an increased risk of lymphoma, particularly with long-term use," the investigators said.

Long-term follow-up studies are needed in children to assess whether lymphoma risk is exposure dependent – as suggested by the existing literature – rather than a cumulative risk that is dependent on duration of therapy, they added.

Dr. Dulai reported having no disclosures. Coauthor Dr. Corey Siegel reported serving as an advisory board member or consultant for, and/or receiving grant support from Abbvie, Janssen, UCB, and the Agency for Healthcare Research and Quality. Dr. Marla Dubinsky serves as a consultant for Abbvie, Janssen, UCB, and Takeda.

The risk of lymphoma is no greater in children with inflammatory bowel disease who are treated with anti–tumor necrosis factor therapy than in adults treated with anti-TNF therapies or in children treated with other therapies for IBD, according to findings from a systematic review.

The review, which included 65 studies involving a total of 5,528 patients with 9,516 patient-years of follow-up, also showed that the rate of serious infection was lower among children with IBD who were treated with anti-TNF agents than among those treated with steroids or among adults treated with anti-TNF agents, Dr. Parambir S. Dulai of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2014.01.021).

Source: American Gastroenterological Association

Two patients developed lymphoma, for a rate of 2.1/10,000 patient-years of follow-up (PYF), which did not differ significantly from the expected rate among children (5.8/100,000 PYF), the rate among pediatric patients receiving thiopurine monotherapy (4.5/10,000), or the rate among adults treated with anti-TNF agents (6.1/10,000), the investigators found.

The rate of serious infections was 352/10,000 PYF in pediatric patients treated with anti-TNF agents as part of prospective studies included in the review, which was similar to the expected rate in those treated with immunomodulator therapy (333/10,000 PYF), and significantly lower than the expected rate in those treated with glucocorticoids (730/10,000 PYF) and adults treated with anti-TNF agents (654/10,000 PYF).

Of seven deaths that occurred among the patients, five were considered related to treatment (four cases of sepsis, one case of arrhythmia), for a rate of 5.3/10,000 PYF.

Although anti-TNF therapy is an effective treatment option for pediatric IBD, many physicians are hesitant about prescribing anti-TNFs to children because of concerns about infection and lymphoma risk based on the adult literature and case reports of hepatosplenic T-cell lymphoma. However, the findings of this pooled analysis suggest that such concerns may be unfounded.

Older age, sex, and duration of IBD have been linked with increased risk of lymphoproliferative disorders and could help explain the observed differences between adults and pediatric IBD patients with respect to lymphoma rates after anti-TNF exposure, the investigators said.

"Overall, the risk of serious infection, lymphoma, and death with anti-TNF therapy in pediatric IBD is very low," they wrote.

However, they noted that the study is limited by a number of factors, including short duration of per-person follow-up, which means that while the data are promising, they are "not definitive in answering the question of whether anti-TNF therapy is associated with an increased risk of lymphoma, particularly with long-term use," the investigators said.

Long-term follow-up studies are needed in children to assess whether lymphoma risk is exposure dependent – as suggested by the existing literature – rather than a cumulative risk that is dependent on duration of therapy, they added.

Dr. Dulai reported having no disclosures. Coauthor Dr. Corey Siegel reported serving as an advisory board member or consultant for, and/or receiving grant support from Abbvie, Janssen, UCB, and the Agency for Healthcare Research and Quality. Dr. Marla Dubinsky serves as a consultant for Abbvie, Janssen, UCB, and Takeda.

The risk of lymphoma is no greater in children with inflammatory bowel disease who are treated with anti–tumor necrosis factor therapy than in adults treated with anti-TNF therapies or in children treated with other therapies for IBD, according to findings from a systematic review.

The review, which included 65 studies involving a total of 5,528 patients with 9,516 patient-years of follow-up, also showed that the rate of serious infection was lower among children with IBD who were treated with anti-TNF agents than among those treated with steroids or among adults treated with anti-TNF agents, Dr. Parambir S. Dulai of Dartmouth-Hitchcock Medical Center, Lebanon, N.H., and his colleagues reported in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2014.01.021).

Source: American Gastroenterological Association

Two patients developed lymphoma, for a rate of 2.1/10,000 patient-years of follow-up (PYF), which did not differ significantly from the expected rate among children (5.8/100,000 PYF), the rate among pediatric patients receiving thiopurine monotherapy (4.5/10,000), or the rate among adults treated with anti-TNF agents (6.1/10,000), the investigators found.

The rate of serious infections was 352/10,000 PYF in pediatric patients treated with anti-TNF agents as part of prospective studies included in the review, which was similar to the expected rate in those treated with immunomodulator therapy (333/10,000 PYF), and significantly lower than the expected rate in those treated with glucocorticoids (730/10,000 PYF) and adults treated with anti-TNF agents (654/10,000 PYF).

Of seven deaths that occurred among the patients, five were considered related to treatment (four cases of sepsis, one case of arrhythmia), for a rate of 5.3/10,000 PYF.

Although anti-TNF therapy is an effective treatment option for pediatric IBD, many physicians are hesitant about prescribing anti-TNFs to children because of concerns about infection and lymphoma risk based on the adult literature and case reports of hepatosplenic T-cell lymphoma. However, the findings of this pooled analysis suggest that such concerns may be unfounded.

Older age, sex, and duration of IBD have been linked with increased risk of lymphoproliferative disorders and could help explain the observed differences between adults and pediatric IBD patients with respect to lymphoma rates after anti-TNF exposure, the investigators said.

"Overall, the risk of serious infection, lymphoma, and death with anti-TNF therapy in pediatric IBD is very low," they wrote.

However, they noted that the study is limited by a number of factors, including short duration of per-person follow-up, which means that while the data are promising, they are "not definitive in answering the question of whether anti-TNF therapy is associated with an increased risk of lymphoma, particularly with long-term use," the investigators said.

Long-term follow-up studies are needed in children to assess whether lymphoma risk is exposure dependent – as suggested by the existing literature – rather than a cumulative risk that is dependent on duration of therapy, they added.

Dr. Dulai reported having no disclosures. Coauthor Dr. Corey Siegel reported serving as an advisory board member or consultant for, and/or receiving grant support from Abbvie, Janssen, UCB, and the Agency for Healthcare Research and Quality. Dr. Marla Dubinsky serves as a consultant for Abbvie, Janssen, UCB, and Takeda.

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

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

Source: American Gastroenterological Association

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

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

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

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

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

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

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

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

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

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

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

Source: American Gastroenterological Association

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

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

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

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

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

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

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

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

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

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

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

Source: American Gastroenterological Association

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

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

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

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

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

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

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

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

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

Fecal microbiota transplantation successfully treated severe and/or complicated Clostridium difficile infection in a retrospective, multicenter, long-term follow-up study of 17 patients in whom conventional therapy had failed.

The 14 inpatients and 3 outpatients were treated for either severe or complicated C. difficile infection (4 patients) or for both severe and complicated infection (13 patients). They were followed for a mean of 11 months (ranging from 1 to 42 months) after fecal microbiota transplantation.

In 16 patients with diarrhea before transplantation, the diarrhea resolved in 12 patients over an average of 6 days after fecal microbiota transplantation and improved in 4 patients. In 11 patients with abdominal pain before transplantation, the pain resolved in 8 patients over a mean of 10 days and improved in 3 patients, Dr. Olga C. Aroniadis and her associates reported.

Fifteen of 17 patients had no recurrence of C. difficile infection within 90 days of transplantation, for a primary cure rate of 88%. One of the two patients with a recurrence within 90 days was treated successfully with a second fecal microbiota transplantation, for a secondary cure rate of 94%, said Dr. Aroniadis of Montefiore Medical Center, New York.

Patients were considered cured if symptoms of C. difficile infection resolved or improved enough for the patient to be discharged from the hospital, she said in an interview. "In some patients, bowel habits do not return to baseline after successful treatment of C. difficile infection and patients have intermittent diarrhea and soft stools, but these patients no longer have C. difficile. This is what we experienced with some of our patients who we considered to be cured," she said.

One patient developed a late recurrence (more than 90 days after initial transplantation) in association with taking antibiotics to treat diverticulitis. The recurrent C. difficile infection was treated successfully with repeat fecal microbiota transplantation.

Dr. Aroniadis reported the results at the James W. Freston conference sponsored by the American Gastroenterological Association.

The cure rates are similar to results in previous studies of patients who underwent fecal microbiota transplantation for recurrent C. difficile infection who did not have severe or complicated disease, she said.

The 17 patients in the current study had failed conventional medical therapy with antibiotics such as metronidazole and oral vancomycin prior to fecal microbiota transplantation. Many were hospitalized in the ICU and on vasopressor support, she said.

"It’s truly a rewarding experience to watch these severely ill patients improve after fecal transplantation," Dr. Aroniadis said. "Fecal transplantation even obviated the need for colectomy in one of our patients."

Fecal microbiota transplantation for C. difficile infection can be performed by infusing a donated fecal suspension into the gastrointestinal tract via colonoscopy, upper endoscopy, flexible sigmoidoscopy, or enema. Physicians should "use their clinical judgment when determining the appropriate route of administration in patients with severe or complicated C. difficile infection who may be at increased risk for complications from colonoscopy due to colonic dilation and poor bowel wall integrity," Dr. Aroniadis said.

In the study, C. difficile infection was considered severe if the patient had abdominal tenderness, an albumin level less than 3 g/dL, or a WBC count greater than 15,000 cells/mcL, in accordance with published guidelines, she said. Infection was considered complicated if it necessitated ICU care or if the patient had hypotension with or without the use of vasopressors, a change in mental status, a WBC count greater than 35,000 cells/mcL or less than 2,000 cells/mcL, serum lactate levels of 2.2 mmol/L or greater, end-organ failure, a fever of at least 38.5 °C, or ileus or significant abdominal tenderness.

Patients had a mean age of 66 years (ranging from 38 to 89 years), and 13 of them were women.

Dr. Aroniadis reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Fecal microbiota transplantation successfully treated severe and/or complicated Clostridium difficile infection in a retrospective, multicenter, long-term follow-up study of 17 patients in whom conventional therapy had failed.

The 14 inpatients and 3 outpatients were treated for either severe or complicated C. difficile infection (4 patients) or for both severe and complicated infection (13 patients). They were followed for a mean of 11 months (ranging from 1 to 42 months) after fecal microbiota transplantation.

In 16 patients with diarrhea before transplantation, the diarrhea resolved in 12 patients over an average of 6 days after fecal microbiota transplantation and improved in 4 patients. In 11 patients with abdominal pain before transplantation, the pain resolved in 8 patients over a mean of 10 days and improved in 3 patients, Dr. Olga C. Aroniadis and her associates reported.

Fifteen of 17 patients had no recurrence of C. difficile infection within 90 days of transplantation, for a primary cure rate of 88%. One of the two patients with a recurrence within 90 days was treated successfully with a second fecal microbiota transplantation, for a secondary cure rate of 94%, said Dr. Aroniadis of Montefiore Medical Center, New York.

Patients were considered cured if symptoms of C. difficile infection resolved or improved enough for the patient to be discharged from the hospital, she said in an interview. "In some patients, bowel habits do not return to baseline after successful treatment of C. difficile infection and patients have intermittent diarrhea and soft stools, but these patients no longer have C. difficile. This is what we experienced with some of our patients who we considered to be cured," she said.

One patient developed a late recurrence (more than 90 days after initial transplantation) in association with taking antibiotics to treat diverticulitis. The recurrent C. difficile infection was treated successfully with repeat fecal microbiota transplantation.

Dr. Aroniadis reported the results at the James W. Freston conference sponsored by the American Gastroenterological Association.

The cure rates are similar to results in previous studies of patients who underwent fecal microbiota transplantation for recurrent C. difficile infection who did not have severe or complicated disease, she said.

The 17 patients in the current study had failed conventional medical therapy with antibiotics such as metronidazole and oral vancomycin prior to fecal microbiota transplantation. Many were hospitalized in the ICU and on vasopressor support, she said.

"It’s truly a rewarding experience to watch these severely ill patients improve after fecal transplantation," Dr. Aroniadis said. "Fecal transplantation even obviated the need for colectomy in one of our patients."

Fecal microbiota transplantation for C. difficile infection can be performed by infusing a donated fecal suspension into the gastrointestinal tract via colonoscopy, upper endoscopy, flexible sigmoidoscopy, or enema. Physicians should "use their clinical judgment when determining the appropriate route of administration in patients with severe or complicated C. difficile infection who may be at increased risk for complications from colonoscopy due to colonic dilation and poor bowel wall integrity," Dr. Aroniadis said.

In the study, C. difficile infection was considered severe if the patient had abdominal tenderness, an albumin level less than 3 g/dL, or a WBC count greater than 15,000 cells/mcL, in accordance with published guidelines, she said. Infection was considered complicated if it necessitated ICU care or if the patient had hypotension with or without the use of vasopressors, a change in mental status, a WBC count greater than 35,000 cells/mcL or less than 2,000 cells/mcL, serum lactate levels of 2.2 mmol/L or greater, end-organ failure, a fever of at least 38.5 °C, or ileus or significant abdominal tenderness.

Patients had a mean age of 66 years (ranging from 38 to 89 years), and 13 of them were women.

Dr. Aroniadis reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Fecal microbiota transplantation successfully treated severe and/or complicated Clostridium difficile infection in a retrospective, multicenter, long-term follow-up study of 17 patients in whom conventional therapy had failed.

The 14 inpatients and 3 outpatients were treated for either severe or complicated C. difficile infection (4 patients) or for both severe and complicated infection (13 patients). They were followed for a mean of 11 months (ranging from 1 to 42 months) after fecal microbiota transplantation.

In 16 patients with diarrhea before transplantation, the diarrhea resolved in 12 patients over an average of 6 days after fecal microbiota transplantation and improved in 4 patients. In 11 patients with abdominal pain before transplantation, the pain resolved in 8 patients over a mean of 10 days and improved in 3 patients, Dr. Olga C. Aroniadis and her associates reported.

Fifteen of 17 patients had no recurrence of C. difficile infection within 90 days of transplantation, for a primary cure rate of 88%. One of the two patients with a recurrence within 90 days was treated successfully with a second fecal microbiota transplantation, for a secondary cure rate of 94%, said Dr. Aroniadis of Montefiore Medical Center, New York.

Patients were considered cured if symptoms of C. difficile infection resolved or improved enough for the patient to be discharged from the hospital, she said in an interview. "In some patients, bowel habits do not return to baseline after successful treatment of C. difficile infection and patients have intermittent diarrhea and soft stools, but these patients no longer have C. difficile. This is what we experienced with some of our patients who we considered to be cured," she said.

One patient developed a late recurrence (more than 90 days after initial transplantation) in association with taking antibiotics to treat diverticulitis. The recurrent C. difficile infection was treated successfully with repeat fecal microbiota transplantation.

Dr. Aroniadis reported the results at the James W. Freston conference sponsored by the American Gastroenterological Association.

The cure rates are similar to results in previous studies of patients who underwent fecal microbiota transplantation for recurrent C. difficile infection who did not have severe or complicated disease, she said.

The 17 patients in the current study had failed conventional medical therapy with antibiotics such as metronidazole and oral vancomycin prior to fecal microbiota transplantation. Many were hospitalized in the ICU and on vasopressor support, she said.

"It’s truly a rewarding experience to watch these severely ill patients improve after fecal transplantation," Dr. Aroniadis said. "Fecal transplantation even obviated the need for colectomy in one of our patients."

Fecal microbiota transplantation for C. difficile infection can be performed by infusing a donated fecal suspension into the gastrointestinal tract via colonoscopy, upper endoscopy, flexible sigmoidoscopy, or enema. Physicians should "use their clinical judgment when determining the appropriate route of administration in patients with severe or complicated C. difficile infection who may be at increased risk for complications from colonoscopy due to colonic dilation and poor bowel wall integrity," Dr. Aroniadis said.

In the study, C. difficile infection was considered severe if the patient had abdominal tenderness, an albumin level less than 3 g/dL, or a WBC count greater than 15,000 cells/mcL, in accordance with published guidelines, she said. Infection was considered complicated if it necessitated ICU care or if the patient had hypotension with or without the use of vasopressors, a change in mental status, a WBC count greater than 35,000 cells/mcL or less than 2,000 cells/mcL, serum lactate levels of 2.2 mmol/L or greater, end-organ failure, a fever of at least 38.5 °C, or ileus or significant abdominal tenderness.

Patients had a mean age of 66 years (ranging from 38 to 89 years), and 13 of them were women.

Dr. Aroniadis reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

Medical therapy for the treatment of patients with inflammatory bowel disease has clearly improved the lives of patients and improved outcomes, but does not benefit all patients. Since the initial introduction of corticosteroids and mesalamine derivatives in the 1950s, medical therapy for IBD has improved significantly.

With the widespread use of antimetabolite therapy and the introduction of biologics in 1998 – infliximab, adalimumab, golimumab, certolizumab pegol, natalizumab, and finally vedolizumab – we can induce remission in steroid-dependent and steroid-refractory patients and decrease rates of surgery as well.

The goals of medical therapy have also evolved as the potency of the agents to treat patients with IBD has improved. Initially, symptom control was the desired goal of medical therapy, but soon it was recognized that this was inadequate and mucosal healing became the desired target. Now we recognize that mucosal healing is important while achieving other important endpoints – reduced hospitalization, reduction in surgery, reduced social and occupational burden, and finally doing so with improved safety and tolerability of medications.

Historically, we have used a step-up approach starting with the least effective agents and "stepping up" to more potent therapies. In this model, therapy is stepped up according to severity at presentation or failure at the prior step. We now have the ability to "profile" certain patients and treat those who will have aggressive disease with early aggressive therapy. In Crohn’s disease in particular, we are able to predict which patients will have a more virulent disease course.

Highlights of specific examples from clinical trials of current medical therapies make it very clear that there is a large unmet need for medical treatment of patients with IBD. The data presented focus on well recognized clinical studies from trials in patients with ulcerative colitis; several of these trials led to Food and Drug Administration approval.

A recent study evaluated the addition of oral mesalamine to topical mesalamine in patients with extensive ulcerative colitis, which achieved remission in 44% of patients; leaving 56% of patients with active disease.

Similarly, there were two studies evaluating patients with ulcerative colitis who received budesonide MMX (CORE I and II studies). In these studies, the rates of remission with steroid withdrawal were 17.4% and 17.9%; thus, over 80% of patients did not achieve remission.

In a recent meta-analysis the mean efficacy for azathioprine in ulcerative colitis patients was 60%. In a study using dual therapy of infliximab and azathioprine (SUCCESS trial) monotherapy with azathioprine was able to achieve remission in 24% of patients, infliximab in 22% and combination therapy in only 40% of patients; thus leaving 60% of patients not in remission.

In patients with Crohn’s disease we have similar limitations with current medical therapy. Although azathioprine has been widely used – it has recently been demonstrated to be inadequate as monotherapy for treatment of early Crohn’s disease. The rates of remission are inadequate in patients receiving infliximab (ACCENT I trial) and adalimumab (CHARM Trial) with approximately one-quarter to one-third of patients at most achieving remission. In the SONIC trial, when combination therapy with infliximab and azathioprine was used, remission with steroid-free status was achieved in 57% of patients at week 26 compared with 30% and 45%, respectively, in the azathioprine and infliximab monotherapy treatment arms.

Early aggressive therapy has been demonstrated to achieve higher rates of mucosal healing. We now recognize that it is appropriate to treat early disease, but not in all patients.

We attempt to prognosticate and treat those patients who have a poor prognosis with early aggressive therapy – specifically those patients who have fistulas, early steroid users, smo-ers, those with severe endoscopic lesions, those younger than 40, and those with extensive disease. We attempt to use combination therapy (anti-TNFs and immunomodulators) when appropriate given the added benefits: specifically, higher drug levels, fewer acute side effects, fewer infusion reactions, fewer serious infections, and also better efficacy.

Our efforts to optimize the use of treatment agents involve monitoring for antidrug antibodies and if present, switching the patient to different agents; we also monitor drug levels and when low we can increase the frequency of administration or escalate the drug dose.

We recognize that patients who have higher therapeutic trough levels within the therapeutic window are more likely to achieve clinical remission.

Several factors influence anti-TNF pharmacokinetics, including the presence of antidrug antibodies, concomitant use of immunosuppressives, low serum albumin, high baseline CRP concentration, large body size, and male gender.

Medical therapy has lessened the need for patients to undergo bowel surgery.

A recent Danish population cohort study evaluated 48,967 patients with IBD (CD, 13,185 and UC, 35,782) during 1979-2011. The 5-year cumulative probability of the first major surgery decreased from 44.7% in the early cohort (1979-1986) to 19.6% in the later cohort (2003-2011; P less than .001) for Crohn’s disease, and from 11.7% in early cohort to 7.5% in later cohort (P less than .001) for ulcerative colitis.

There are numerous drugs in development with different mechanisms of action for patients with both ulcerative colitis and Crohn’s disease. Too many IBD patients still face surgery, although there has been improvement. We are learning how to better use the medications we have and optimize therapy.

Dr. Lichtenstein is professor of medicine, department of medicine, division of gastroenterology, at the University of Pennsylvania, Philadelphia, and director of the IBD program at the university. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Medical therapy for the treatment of patients with inflammatory bowel disease has clearly improved the lives of patients and improved outcomes, but does not benefit all patients. Since the initial introduction of corticosteroids and mesalamine derivatives in the 1950s, medical therapy for IBD has improved significantly.

With the widespread use of antimetabolite therapy and the introduction of biologics in 1998 – infliximab, adalimumab, golimumab, certolizumab pegol, natalizumab, and finally vedolizumab – we can induce remission in steroid-dependent and steroid-refractory patients and decrease rates of surgery as well.

The goals of medical therapy have also evolved as the potency of the agents to treat patients with IBD has improved. Initially, symptom control was the desired goal of medical therapy, but soon it was recognized that this was inadequate and mucosal healing became the desired target. Now we recognize that mucosal healing is important while achieving other important endpoints – reduced hospitalization, reduction in surgery, reduced social and occupational burden, and finally doing so with improved safety and tolerability of medications.

Historically, we have used a step-up approach starting with the least effective agents and "stepping up" to more potent therapies. In this model, therapy is stepped up according to severity at presentation or failure at the prior step. We now have the ability to "profile" certain patients and treat those who will have aggressive disease with early aggressive therapy. In Crohn’s disease in particular, we are able to predict which patients will have a more virulent disease course.

Highlights of specific examples from clinical trials of current medical therapies make it very clear that there is a large unmet need for medical treatment of patients with IBD. The data presented focus on well recognized clinical studies from trials in patients with ulcerative colitis; several of these trials led to Food and Drug Administration approval.

A recent study evaluated the addition of oral mesalamine to topical mesalamine in patients with extensive ulcerative colitis, which achieved remission in 44% of patients; leaving 56% of patients with active disease.

Similarly, there were two studies evaluating patients with ulcerative colitis who received budesonide MMX (CORE I and II studies). In these studies, the rates of remission with steroid withdrawal were 17.4% and 17.9%; thus, over 80% of patients did not achieve remission.

In a recent meta-analysis the mean efficacy for azathioprine in ulcerative colitis patients was 60%. In a study using dual therapy of infliximab and azathioprine (SUCCESS trial) monotherapy with azathioprine was able to achieve remission in 24% of patients, infliximab in 22% and combination therapy in only 40% of patients; thus leaving 60% of patients not in remission.

In patients with Crohn’s disease we have similar limitations with current medical therapy. Although azathioprine has been widely used – it has recently been demonstrated to be inadequate as monotherapy for treatment of early Crohn’s disease. The rates of remission are inadequate in patients receiving infliximab (ACCENT I trial) and adalimumab (CHARM Trial) with approximately one-quarter to one-third of patients at most achieving remission. In the SONIC trial, when combination therapy with infliximab and azathioprine was used, remission with steroid-free status was achieved in 57% of patients at week 26 compared with 30% and 45%, respectively, in the azathioprine and infliximab monotherapy treatment arms.

Early aggressive therapy has been demonstrated to achieve higher rates of mucosal healing. We now recognize that it is appropriate to treat early disease, but not in all patients.

We attempt to prognosticate and treat those patients who have a poor prognosis with early aggressive therapy – specifically those patients who have fistulas, early steroid users, smo-ers, those with severe endoscopic lesions, those younger than 40, and those with extensive disease. We attempt to use combination therapy (anti-TNFs and immunomodulators) when appropriate given the added benefits: specifically, higher drug levels, fewer acute side effects, fewer infusion reactions, fewer serious infections, and also better efficacy.

Our efforts to optimize the use of treatment agents involve monitoring for antidrug antibodies and if present, switching the patient to different agents; we also monitor drug levels and when low we can increase the frequency of administration or escalate the drug dose.

We recognize that patients who have higher therapeutic trough levels within the therapeutic window are more likely to achieve clinical remission.

Several factors influence anti-TNF pharmacokinetics, including the presence of antidrug antibodies, concomitant use of immunosuppressives, low serum albumin, high baseline CRP concentration, large body size, and male gender.

Medical therapy has lessened the need for patients to undergo bowel surgery.

A recent Danish population cohort study evaluated 48,967 patients with IBD (CD, 13,185 and UC, 35,782) during 1979-2011. The 5-year cumulative probability of the first major surgery decreased from 44.7% in the early cohort (1979-1986) to 19.6% in the later cohort (2003-2011; P less than .001) for Crohn’s disease, and from 11.7% in early cohort to 7.5% in later cohort (P less than .001) for ulcerative colitis.

There are numerous drugs in development with different mechanisms of action for patients with both ulcerative colitis and Crohn’s disease. Too many IBD patients still face surgery, although there has been improvement. We are learning how to better use the medications we have and optimize therapy.

Dr. Lichtenstein is professor of medicine, department of medicine, division of gastroenterology, at the University of Pennsylvania, Philadelphia, and director of the IBD program at the university. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Medical therapy for the treatment of patients with inflammatory bowel disease has clearly improved the lives of patients and improved outcomes, but does not benefit all patients. Since the initial introduction of corticosteroids and mesalamine derivatives in the 1950s, medical therapy for IBD has improved significantly.

With the widespread use of antimetabolite therapy and the introduction of biologics in 1998 – infliximab, adalimumab, golimumab, certolizumab pegol, natalizumab, and finally vedolizumab – we can induce remission in steroid-dependent and steroid-refractory patients and decrease rates of surgery as well.

The goals of medical therapy have also evolved as the potency of the agents to treat patients with IBD has improved. Initially, symptom control was the desired goal of medical therapy, but soon it was recognized that this was inadequate and mucosal healing became the desired target. Now we recognize that mucosal healing is important while achieving other important endpoints – reduced hospitalization, reduction in surgery, reduced social and occupational burden, and finally doing so with improved safety and tolerability of medications.

Historically, we have used a step-up approach starting with the least effective agents and "stepping up" to more potent therapies. In this model, therapy is stepped up according to severity at presentation or failure at the prior step. We now have the ability to "profile" certain patients and treat those who will have aggressive disease with early aggressive therapy. In Crohn’s disease in particular, we are able to predict which patients will have a more virulent disease course.

Highlights of specific examples from clinical trials of current medical therapies make it very clear that there is a large unmet need for medical treatment of patients with IBD. The data presented focus on well recognized clinical studies from trials in patients with ulcerative colitis; several of these trials led to Food and Drug Administration approval.

A recent study evaluated the addition of oral mesalamine to topical mesalamine in patients with extensive ulcerative colitis, which achieved remission in 44% of patients; leaving 56% of patients with active disease.

Similarly, there were two studies evaluating patients with ulcerative colitis who received budesonide MMX (CORE I and II studies). In these studies, the rates of remission with steroid withdrawal were 17.4% and 17.9%; thus, over 80% of patients did not achieve remission.

In a recent meta-analysis the mean efficacy for azathioprine in ulcerative colitis patients was 60%. In a study using dual therapy of infliximab and azathioprine (SUCCESS trial) monotherapy with azathioprine was able to achieve remission in 24% of patients, infliximab in 22% and combination therapy in only 40% of patients; thus leaving 60% of patients not in remission.

In patients with Crohn’s disease we have similar limitations with current medical therapy. Although azathioprine has been widely used – it has recently been demonstrated to be inadequate as monotherapy for treatment of early Crohn’s disease. The rates of remission are inadequate in patients receiving infliximab (ACCENT I trial) and adalimumab (CHARM Trial) with approximately one-quarter to one-third of patients at most achieving remission. In the SONIC trial, when combination therapy with infliximab and azathioprine was used, remission with steroid-free status was achieved in 57% of patients at week 26 compared with 30% and 45%, respectively, in the azathioprine and infliximab monotherapy treatment arms.

Early aggressive therapy has been demonstrated to achieve higher rates of mucosal healing. We now recognize that it is appropriate to treat early disease, but not in all patients.

We attempt to prognosticate and treat those patients who have a poor prognosis with early aggressive therapy – specifically those patients who have fistulas, early steroid users, smo-ers, those with severe endoscopic lesions, those younger than 40, and those with extensive disease. We attempt to use combination therapy (anti-TNFs and immunomodulators) when appropriate given the added benefits: specifically, higher drug levels, fewer acute side effects, fewer infusion reactions, fewer serious infections, and also better efficacy.

Our efforts to optimize the use of treatment agents involve monitoring for antidrug antibodies and if present, switching the patient to different agents; we also monitor drug levels and when low we can increase the frequency of administration or escalate the drug dose.

We recognize that patients who have higher therapeutic trough levels within the therapeutic window are more likely to achieve clinical remission.

Several factors influence anti-TNF pharmacokinetics, including the presence of antidrug antibodies, concomitant use of immunosuppressives, low serum albumin, high baseline CRP concentration, large body size, and male gender.

Medical therapy has lessened the need for patients to undergo bowel surgery.

A recent Danish population cohort study evaluated 48,967 patients with IBD (CD, 13,185 and UC, 35,782) during 1979-2011. The 5-year cumulative probability of the first major surgery decreased from 44.7% in the early cohort (1979-1986) to 19.6% in the later cohort (2003-2011; P less than .001) for Crohn’s disease, and from 11.7% in early cohort to 7.5% in later cohort (P less than .001) for ulcerative colitis.

There are numerous drugs in development with different mechanisms of action for patients with both ulcerative colitis and Crohn’s disease. Too many IBD patients still face surgery, although there has been improvement. We are learning how to better use the medications we have and optimize therapy.

Dr. Lichtenstein is professor of medicine, department of medicine, division of gastroenterology, at the University of Pennsylvania, Philadelphia, and director of the IBD program at the university. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

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

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

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

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

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

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

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

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

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

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

ginews@gastro.org

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

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

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

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

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

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

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

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

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

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

ginews@gastro.org

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

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

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

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

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

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

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

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

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

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

ginews@gastro.org

In an urban colorectal surgery department, a near-doubling in the proportion of surgical procedures performed laparoscopically accompanied significant declines in both severe postoperative morbidity and conversions to laparotomy, in a 14-year, single-hospital study reported in Annals of Surgery.

"This study demonstrated that a laparoscopic approach is a safe and effective alternative to open surgery" for management of inflammatory bowel disease (IBD), wrote Dr. León Maggiori and his associates at the Assistance Publique-Hôpitaux de Paris.

©avatavat/thinkstockphotos.com

"Associated postoperative morbidity was comparable to reported rates after open approach," the researchers added.

Dr. Maggiori and his associates studied 790 consecutive intestinal resections for IBD performed on 633 patients between June 1998 and July 2012. About two-thirds of the procedures were for Crohn’s disease, and one-third were for ulcerative colitis, the investigators said (Ann. Surg. 2014;260:305-10). The proportion of laparoscopically performed procedures rose from 42% to 80% during the study period (P less than .001), and the trend occurred both for Crohn’s and for ulcerative colitis cases, they added.

As surgeons accrued experience, the rate of complex cases performed laparoscopically also approximately doubled (from 16% to 33%; P less than .023), the researchers said. Furthermore, the mean adjusted risk of conversion to open surgery fell significantly (from 18% to 6%; P less than .001), as did the rate of severe postoperative morbidity (from 14% to 8%; P less than .001).

In all, 12% of laparoscopic cases required conversion, most often because of abscesses or fistulas found during surgery or difficulty dissecting adhesions, the investigators said. Thirteen percent of laparoscopies led to severe postoperative morbidity, defined as Clavien-Dindo grade 3 or 4 complications, they added. The single postoperative death occurred in a patient who developed peritonitis and septic shock 3 days after laparoscopic colectomy with ileosigmoidostomy, the researchers said.

The hospital now uses laparoscopy as the standard approach for surgical management of IBD, except in cases of complicated acute colitis, Dr. Maggiori and his associates said.

The limited number of straight open surgical cases meant that they could not directly be compared with laparoscopy, said the investigators, adding that they lacked data on long-term outcomes because many patients underwent surgery in 2008 or later.

The Association François Aupetit partially funded the study. The authors reported having no conflicts of interest.

In an urban colorectal surgery department, a near-doubling in the proportion of surgical procedures performed laparoscopically accompanied significant declines in both severe postoperative morbidity and conversions to laparotomy, in a 14-year, single-hospital study reported in Annals of Surgery.

"This study demonstrated that a laparoscopic approach is a safe and effective alternative to open surgery" for management of inflammatory bowel disease (IBD), wrote Dr. León Maggiori and his associates at the Assistance Publique-Hôpitaux de Paris.

©avatavat/thinkstockphotos.com

"Associated postoperative morbidity was comparable to reported rates after open approach," the researchers added.

Dr. Maggiori and his associates studied 790 consecutive intestinal resections for IBD performed on 633 patients between June 1998 and July 2012. About two-thirds of the procedures were for Crohn’s disease, and one-third were for ulcerative colitis, the investigators said (Ann. Surg. 2014;260:305-10). The proportion of laparoscopically performed procedures rose from 42% to 80% during the study period (P less than .001), and the trend occurred both for Crohn’s and for ulcerative colitis cases, they added.

As surgeons accrued experience, the rate of complex cases performed laparoscopically also approximately doubled (from 16% to 33%; P less than .023), the researchers said. Furthermore, the mean adjusted risk of conversion to open surgery fell significantly (from 18% to 6%; P less than .001), as did the rate of severe postoperative morbidity (from 14% to 8%; P less than .001).

In all, 12% of laparoscopic cases required conversion, most often because of abscesses or fistulas found during surgery or difficulty dissecting adhesions, the investigators said. Thirteen percent of laparoscopies led to severe postoperative morbidity, defined as Clavien-Dindo grade 3 or 4 complications, they added. The single postoperative death occurred in a patient who developed peritonitis and septic shock 3 days after laparoscopic colectomy with ileosigmoidostomy, the researchers said.

The hospital now uses laparoscopy as the standard approach for surgical management of IBD, except in cases of complicated acute colitis, Dr. Maggiori and his associates said.

The limited number of straight open surgical cases meant that they could not directly be compared with laparoscopy, said the investigators, adding that they lacked data on long-term outcomes because many patients underwent surgery in 2008 or later.

The Association François Aupetit partially funded the study. The authors reported having no conflicts of interest.

In an urban colorectal surgery department, a near-doubling in the proportion of surgical procedures performed laparoscopically accompanied significant declines in both severe postoperative morbidity and conversions to laparotomy, in a 14-year, single-hospital study reported in Annals of Surgery.

"This study demonstrated that a laparoscopic approach is a safe and effective alternative to open surgery" for management of inflammatory bowel disease (IBD), wrote Dr. León Maggiori and his associates at the Assistance Publique-Hôpitaux de Paris.

©avatavat/thinkstockphotos.com

"Associated postoperative morbidity was comparable to reported rates after open approach," the researchers added.

Dr. Maggiori and his associates studied 790 consecutive intestinal resections for IBD performed on 633 patients between June 1998 and July 2012. About two-thirds of the procedures were for Crohn’s disease, and one-third were for ulcerative colitis, the investigators said (Ann. Surg. 2014;260:305-10). The proportion of laparoscopically performed procedures rose from 42% to 80% during the study period (P less than .001), and the trend occurred both for Crohn’s and for ulcerative colitis cases, they added.

As surgeons accrued experience, the rate of complex cases performed laparoscopically also approximately doubled (from 16% to 33%; P less than .023), the researchers said. Furthermore, the mean adjusted risk of conversion to open surgery fell significantly (from 18% to 6%; P less than .001), as did the rate of severe postoperative morbidity (from 14% to 8%; P less than .001).

In all, 12% of laparoscopic cases required conversion, most often because of abscesses or fistulas found during surgery or difficulty dissecting adhesions, the investigators said. Thirteen percent of laparoscopies led to severe postoperative morbidity, defined as Clavien-Dindo grade 3 or 4 complications, they added. The single postoperative death occurred in a patient who developed peritonitis and septic shock 3 days after laparoscopic colectomy with ileosigmoidostomy, the researchers said.

The hospital now uses laparoscopy as the standard approach for surgical management of IBD, except in cases of complicated acute colitis, Dr. Maggiori and his associates said.

The limited number of straight open surgical cases meant that they could not directly be compared with laparoscopy, said the investigators, adding that they lacked data on long-term outcomes because many patients underwent surgery in 2008 or later.

The Association François Aupetit partially funded the study. The authors reported having no conflicts of interest.

A hospital’s program to enhance recovery after colorectal surgery cut length of stay by 3 days and saved up to $4,800 per patient without increasing postoperative morbidity or 30-day readmission rates, investigators reported online July 23 in JAMA Surgery.

The study extends the evidence base for colorectal enhanced recovery after surgery (ERAS) programs to community hospital settings, said Dr. Cristina Geltzeiler of Oregon Health and Science University in Portland and her associates.

The investigators studied practice patterns and patient outcomes for 1 year before and 2 years after starting a colorectal ERAS program for 244 patients. The program featured preadmission patient education, preoperative bowel preparation for left-sided and rectal procedures, use of intrathecal spinal anesthetics, conservative fluid management, minimal use of narcotics, and early resumption of oral intake and ambulation after surgery, the researchers reported (JAMA Surg. 2014 July 23 [doi: 10.1001/jamasurg.2014.675]). Discharge criteria did not change, they noted.

After program implementation, use of laparoscopy increased by almost 30% (from 57.4% to 88.8%; P less than .001) and length of stay fell by 3 days (from 6.7 to 3.7 days; P less than .001), while 30-day readmission rates did not increase (17.6% vs. 12.5%), the investigators reported.

The percentage of patients who used postoperative narcotic analgesia also fell substantially (from 63.2% to 15%; P less than .001), as did duration of narcotic use (from 67.8 hours to 47.1 hours; P = .02), ileus (from 13.2% to 2.5% of patients; P = .02) and intra-abdominal infections (from 7.4% to 2.5% of patients; P = .24), the investigators said. Outcomes did not differ significantly for patients with colorectal cancer, they added.

"Development and implementation of the program required multidisciplinary collaboration among surgeons, nursing staff, anesthesia providers, pharmacists, operating room staff, clinics, and preadmission services," said Dr. Geltzeiler and her associates. To gain program buy-in, leaders organized discussions and presentations of published ERAS literature, and also used clear, consistent messaging about expectations for patients’ activity, diet, and pain management throughout the perioperative period, the researchers added.

A trend toward referring patients to a smaller pool of colorectal specialists during the study period could have affected results, the investigators noted. They added that rates of superficial wound infection were probably underreported because such infections tend to occur after discharge.

The authors reported no funding sources or conflicts of interest.

A hospital’s program to enhance recovery after colorectal surgery cut length of stay by 3 days and saved up to $4,800 per patient without increasing postoperative morbidity or 30-day readmission rates, investigators reported online July 23 in JAMA Surgery.

The study extends the evidence base for colorectal enhanced recovery after surgery (ERAS) programs to community hospital settings, said Dr. Cristina Geltzeiler of Oregon Health and Science University in Portland and her associates.

The investigators studied practice patterns and patient outcomes for 1 year before and 2 years after starting a colorectal ERAS program for 244 patients. The program featured preadmission patient education, preoperative bowel preparation for left-sided and rectal procedures, use of intrathecal spinal anesthetics, conservative fluid management, minimal use of narcotics, and early resumption of oral intake and ambulation after surgery, the researchers reported (JAMA Surg. 2014 July 23 [doi: 10.1001/jamasurg.2014.675]). Discharge criteria did not change, they noted.

After program implementation, use of laparoscopy increased by almost 30% (from 57.4% to 88.8%; P less than .001) and length of stay fell by 3 days (from 6.7 to 3.7 days; P less than .001), while 30-day readmission rates did not increase (17.6% vs. 12.5%), the investigators reported.

The percentage of patients who used postoperative narcotic analgesia also fell substantially (from 63.2% to 15%; P less than .001), as did duration of narcotic use (from 67.8 hours to 47.1 hours; P = .02), ileus (from 13.2% to 2.5% of patients; P = .02) and intra-abdominal infections (from 7.4% to 2.5% of patients; P = .24), the investigators said. Outcomes did not differ significantly for patients with colorectal cancer, they added.

"Development and implementation of the program required multidisciplinary collaboration among surgeons, nursing staff, anesthesia providers, pharmacists, operating room staff, clinics, and preadmission services," said Dr. Geltzeiler and her associates. To gain program buy-in, leaders organized discussions and presentations of published ERAS literature, and also used clear, consistent messaging about expectations for patients’ activity, diet, and pain management throughout the perioperative period, the researchers added.

A trend toward referring patients to a smaller pool of colorectal specialists during the study period could have affected results, the investigators noted. They added that rates of superficial wound infection were probably underreported because such infections tend to occur after discharge.

The authors reported no funding sources or conflicts of interest.

A hospital’s program to enhance recovery after colorectal surgery cut length of stay by 3 days and saved up to $4,800 per patient without increasing postoperative morbidity or 30-day readmission rates, investigators reported online July 23 in JAMA Surgery.

The study extends the evidence base for colorectal enhanced recovery after surgery (ERAS) programs to community hospital settings, said Dr. Cristina Geltzeiler of Oregon Health and Science University in Portland and her associates.

The investigators studied practice patterns and patient outcomes for 1 year before and 2 years after starting a colorectal ERAS program for 244 patients. The program featured preadmission patient education, preoperative bowel preparation for left-sided and rectal procedures, use of intrathecal spinal anesthetics, conservative fluid management, minimal use of narcotics, and early resumption of oral intake and ambulation after surgery, the researchers reported (JAMA Surg. 2014 July 23 [doi: 10.1001/jamasurg.2014.675]). Discharge criteria did not change, they noted.

After program implementation, use of laparoscopy increased by almost 30% (from 57.4% to 88.8%; P less than .001) and length of stay fell by 3 days (from 6.7 to 3.7 days; P less than .001), while 30-day readmission rates did not increase (17.6% vs. 12.5%), the investigators reported.

The percentage of patients who used postoperative narcotic analgesia also fell substantially (from 63.2% to 15%; P less than .001), as did duration of narcotic use (from 67.8 hours to 47.1 hours; P = .02), ileus (from 13.2% to 2.5% of patients; P = .02) and intra-abdominal infections (from 7.4% to 2.5% of patients; P = .24), the investigators said. Outcomes did not differ significantly for patients with colorectal cancer, they added.

"Development and implementation of the program required multidisciplinary collaboration among surgeons, nursing staff, anesthesia providers, pharmacists, operating room staff, clinics, and preadmission services," said Dr. Geltzeiler and her associates. To gain program buy-in, leaders organized discussions and presentations of published ERAS literature, and also used clear, consistent messaging about expectations for patients’ activity, diet, and pain management throughout the perioperative period, the researchers added.

A trend toward referring patients to a smaller pool of colorectal specialists during the study period could have affected results, the investigators noted. They added that rates of superficial wound infection were probably underreported because such infections tend to occur after discharge.

The authors reported no funding sources or conflicts of interest.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is manifested by abdominal pain and altered bowel habits. Many IBS patients report meal-related exacerbations in symptoms, which may be due to true food intolerances but can be also due to visceral hypersensitivity or changes in gut microbiota. Gut microbiota can be significantly altered by changing the intake of fiber and fermentable oligosaccharides, disaccharides, monosaccharides and polyols, referred to by the acronym FODMAPs. High-FODMAP foods include those with excess fructose (e.g., honey, peaches, dried fruits), fructans (e.g., wheat, rye, onions), sorbitol (e.g., apricots, prunes, sweeteners), and raffinose (e.g., lentils, cabbage, legumes).

A high-FODMAP diet can result in increased gas and colonic distension from bacterial fermentation, and increased water in the small bowel due to the high osmotic load. In one study, a high-FODMAP diet was associated with higher levels of breath hydrogen compared with a low-FODMAP diet in both IBS patients and healthy controls, but it only induced GI symptoms and lethargy in IBS patients (J. Gastroenterol. Hepatol. 2010;25:1366-73). Dr. Murray and colleagues (Am. J. Gastroenterol. 2014;109:110-9) measured breath hydrogen as well as small bowel water content and colonic gas and distension using magnetic resonance imaging (MRI) scans of the abdomen in healthy volunteers. Intake of fructose, which has a high osmotic load, was associated with increased small bowel water content compared with glucose and inulin (osmotically inactive fructan). However, inulin increased breath hydrogen and colonic gas to a greater extent than fructose and glucose.

Studies have demonstrated a beneficial effect of a low-FODMAP diet in IBS patients. In one study, IBS patients who followed a low-FODMAP diet reported a better overall and individual symptom response (i.e., bloating, abdominal pain, and flatulence) compared with patients on a standard diet (J. Hum. Nutr. Diet. 2011;5:487-95). A recent crossover trial conducted in Australia compared a low-FODMAP diet to a typical Australian diet, which included high-FODMAP foods, for 21 days each (Gastroenterology 2014;146:67-75). Patients with IBS (n = 30) had lower GI symptom scores on a low-FODMAP diet compared with the Australian diet. Seventy-five percent of the IBS patients had evidence of fructose malabsorption but this did not have an effect on their response to a low-FODMAP diet.

A beneficial response to a low-FODMAP diet has been speculated to be primarily due to avoiding gluten, however this has not been supported by studies. Some IBS patients have reported significant improvement in GI and non-GI (e.g., tiredness) while on a gluten free diet. Dr. Biesikierski and colleagues (Gastroenterology 2013;145:320-8) conducted a double-blind crossover study in 37 IBS patients with nonceliac gluten sensitivity who were placed on a 2-week trial on a low-FODMAP diet and then randomly assigned to a high-gluten, low-gluten, or control (whey protein) diet for 1 week each. GI symptoms improved in all subjects while on a low-FODMAP diet. Symptoms worsened to a similar degree when the gluten or whey was added to their diets but there was no difference between these groups. The study found that there were no specific or dose-dependent effects of gluten in IBS patients who experienced symptom improvement on a low-FODMAP diet. At the recent Digestive Disease Week meeting, a study by Dr. Piacentino et al. (Gastroenterology suppl 2014;146:S-82) addressed this issue further by comparing GI symptoms (i.e., bloating, abdominal distension and abdominal pain) in IBS patients on a: 1) low-FODMAP, gluten-free diet, 2) a low-FODMAP and normal gluten diet, and 3) a normal-FODMAP and gluten-free diet (n = 20 in each group). A low-FODMAP diet with or without gluten was associated with a significant improvement in bloating, abdominal distension, and abdominal pain, compared to a normal FODMAP and gluten diet. There were no significant differences between the two low-FODMAP diets. The authors concluded that gluten avoidance did not add significant benefit to the low-FODMAP diet.

In summary, limited data, which is mainly comprised of studies with relatively small sample sizes, support IBS symptom improvement with a low-FODMAP diet. Fructose and fructans may have different mechanisms by which they cause symptoms in IBS. The beneficial effect of a low-FODMAP diet does not appear to be predominantly based on gluten avoidance. Lastly, there are no definite biomarkers as of now that are associated with symptom response.

Dr. Chang is professor of digestive diseases/gastroenterology, director of the Digestive Health and Nutrition Clinic and the University of California, Los Angeles, GI Fellowship Training Program, and co-director of the Center for Neurobiology of Stress, all at UCLA. Her comments were made at the annual Digestive Disease Week during the ASGE and AGA joint Presidential Plenary.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is manifested by abdominal pain and altered bowel habits. Many IBS patients report meal-related exacerbations in symptoms, which may be due to true food intolerances but can be also due to visceral hypersensitivity or changes in gut microbiota. Gut microbiota can be significantly altered by changing the intake of fiber and fermentable oligosaccharides, disaccharides, monosaccharides and polyols, referred to by the acronym FODMAPs. High-FODMAP foods include those with excess fructose (e.g., honey, peaches, dried fruits), fructans (e.g., wheat, rye, onions), sorbitol (e.g., apricots, prunes, sweeteners), and raffinose (e.g., lentils, cabbage, legumes).

A high-FODMAP diet can result in increased gas and colonic distension from bacterial fermentation, and increased water in the small bowel due to the high osmotic load. In one study, a high-FODMAP diet was associated with higher levels of breath hydrogen compared with a low-FODMAP diet in both IBS patients and healthy controls, but it only induced GI symptoms and lethargy in IBS patients (J. Gastroenterol. Hepatol. 2010;25:1366-73). Dr. Murray and colleagues (Am. J. Gastroenterol. 2014;109:110-9) measured breath hydrogen as well as small bowel water content and colonic gas and distension using magnetic resonance imaging (MRI) scans of the abdomen in healthy volunteers. Intake of fructose, which has a high osmotic load, was associated with increased small bowel water content compared with glucose and inulin (osmotically inactive fructan). However, inulin increased breath hydrogen and colonic gas to a greater extent than fructose and glucose.

Studies have demonstrated a beneficial effect of a low-FODMAP diet in IBS patients. In one study, IBS patients who followed a low-FODMAP diet reported a better overall and individual symptom response (i.e., bloating, abdominal pain, and flatulence) compared with patients on a standard diet (J. Hum. Nutr. Diet. 2011;5:487-95). A recent crossover trial conducted in Australia compared a low-FODMAP diet to a typical Australian diet, which included high-FODMAP foods, for 21 days each (Gastroenterology 2014;146:67-75). Patients with IBS (n = 30) had lower GI symptom scores on a low-FODMAP diet compared with the Australian diet. Seventy-five percent of the IBS patients had evidence of fructose malabsorption but this did not have an effect on their response to a low-FODMAP diet.

A beneficial response to a low-FODMAP diet has been speculated to be primarily due to avoiding gluten, however this has not been supported by studies. Some IBS patients have reported significant improvement in GI and non-GI (e.g., tiredness) while on a gluten free diet. Dr. Biesikierski and colleagues (Gastroenterology 2013;145:320-8) conducted a double-blind crossover study in 37 IBS patients with nonceliac gluten sensitivity who were placed on a 2-week trial on a low-FODMAP diet and then randomly assigned to a high-gluten, low-gluten, or control (whey protein) diet for 1 week each. GI symptoms improved in all subjects while on a low-FODMAP diet. Symptoms worsened to a similar degree when the gluten or whey was added to their diets but there was no difference between these groups. The study found that there were no specific or dose-dependent effects of gluten in IBS patients who experienced symptom improvement on a low-FODMAP diet. At the recent Digestive Disease Week meeting, a study by Dr. Piacentino et al. (Gastroenterology suppl 2014;146:S-82) addressed this issue further by comparing GI symptoms (i.e., bloating, abdominal distension and abdominal pain) in IBS patients on a: 1) low-FODMAP, gluten-free diet, 2) a low-FODMAP and normal gluten diet, and 3) a normal-FODMAP and gluten-free diet (n = 20 in each group). A low-FODMAP diet with or without gluten was associated with a significant improvement in bloating, abdominal distension, and abdominal pain, compared to a normal FODMAP and gluten diet. There were no significant differences between the two low-FODMAP diets. The authors concluded that gluten avoidance did not add significant benefit to the low-FODMAP diet.

In summary, limited data, which is mainly comprised of studies with relatively small sample sizes, support IBS symptom improvement with a low-FODMAP diet. Fructose and fructans may have different mechanisms by which they cause symptoms in IBS. The beneficial effect of a low-FODMAP diet does not appear to be predominantly based on gluten avoidance. Lastly, there are no definite biomarkers as of now that are associated with symptom response.

Dr. Chang is professor of digestive diseases/gastroenterology, director of the Digestive Health and Nutrition Clinic and the University of California, Los Angeles, GI Fellowship Training Program, and co-director of the Center for Neurobiology of Stress, all at UCLA. Her comments were made at the annual Digestive Disease Week during the ASGE and AGA joint Presidential Plenary.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is manifested by abdominal pain and altered bowel habits. Many IBS patients report meal-related exacerbations in symptoms, which may be due to true food intolerances but can be also due to visceral hypersensitivity or changes in gut microbiota. Gut microbiota can be significantly altered by changing the intake of fiber and fermentable oligosaccharides, disaccharides, monosaccharides and polyols, referred to by the acronym FODMAPs. High-FODMAP foods include those with excess fructose (e.g., honey, peaches, dried fruits), fructans (e.g., wheat, rye, onions), sorbitol (e.g., apricots, prunes, sweeteners), and raffinose (e.g., lentils, cabbage, legumes).

A high-FODMAP diet can result in increased gas and colonic distension from bacterial fermentation, and increased water in the small bowel due to the high osmotic load. In one study, a high-FODMAP diet was associated with higher levels of breath hydrogen compared with a low-FODMAP diet in both IBS patients and healthy controls, but it only induced GI symptoms and lethargy in IBS patients (J. Gastroenterol. Hepatol. 2010;25:1366-73). Dr. Murray and colleagues (Am. J. Gastroenterol. 2014;109:110-9) measured breath hydrogen as well as small bowel water content and colonic gas and distension using magnetic resonance imaging (MRI) scans of the abdomen in healthy volunteers. Intake of fructose, which has a high osmotic load, was associated with increased small bowel water content compared with glucose and inulin (osmotically inactive fructan). However, inulin increased breath hydrogen and colonic gas to a greater extent than fructose and glucose.

Studies have demonstrated a beneficial effect of a low-FODMAP diet in IBS patients. In one study, IBS patients who followed a low-FODMAP diet reported a better overall and individual symptom response (i.e., bloating, abdominal pain, and flatulence) compared with patients on a standard diet (J. Hum. Nutr. Diet. 2011;5:487-95). A recent crossover trial conducted in Australia compared a low-FODMAP diet to a typical Australian diet, which included high-FODMAP foods, for 21 days each (Gastroenterology 2014;146:67-75). Patients with IBS (n = 30) had lower GI symptom scores on a low-FODMAP diet compared with the Australian diet. Seventy-five percent of the IBS patients had evidence of fructose malabsorption but this did not have an effect on their response to a low-FODMAP diet.

A beneficial response to a low-FODMAP diet has been speculated to be primarily due to avoiding gluten, however this has not been supported by studies. Some IBS patients have reported significant improvement in GI and non-GI (e.g., tiredness) while on a gluten free diet. Dr. Biesikierski and colleagues (Gastroenterology 2013;145:320-8) conducted a double-blind crossover study in 37 IBS patients with nonceliac gluten sensitivity who were placed on a 2-week trial on a low-FODMAP diet and then randomly assigned to a high-gluten, low-gluten, or control (whey protein) diet for 1 week each. GI symptoms improved in all subjects while on a low-FODMAP diet. Symptoms worsened to a similar degree when the gluten or whey was added to their diets but there was no difference between these groups. The study found that there were no specific or dose-dependent effects of gluten in IBS patients who experienced symptom improvement on a low-FODMAP diet. At the recent Digestive Disease Week meeting, a study by Dr. Piacentino et al. (Gastroenterology suppl 2014;146:S-82) addressed this issue further by comparing GI symptoms (i.e., bloating, abdominal distension and abdominal pain) in IBS patients on a: 1) low-FODMAP, gluten-free diet, 2) a low-FODMAP and normal gluten diet, and 3) a normal-FODMAP and gluten-free diet (n = 20 in each group). A low-FODMAP diet with or without gluten was associated with a significant improvement in bloating, abdominal distension, and abdominal pain, compared to a normal FODMAP and gluten diet. There were no significant differences between the two low-FODMAP diets. The authors concluded that gluten avoidance did not add significant benefit to the low-FODMAP diet.

In summary, limited data, which is mainly comprised of studies with relatively small sample sizes, support IBS symptom improvement with a low-FODMAP diet. Fructose and fructans may have different mechanisms by which they cause symptoms in IBS. The beneficial effect of a low-FODMAP diet does not appear to be predominantly based on gluten avoidance. Lastly, there are no definite biomarkers as of now that are associated with symptom response.

Dr. Chang is professor of digestive diseases/gastroenterology, director of the Digestive Health and Nutrition Clinic and the University of California, Los Angeles, GI Fellowship Training Program, and co-director of the Center for Neurobiology of Stress, all at UCLA. Her comments were made at the annual Digestive Disease Week during the ASGE and AGA joint Presidential Plenary.

Though previously considered fringe medicine and the "last resort" for patients with Clostridium difficile infection, fecal microbiota transplantation (FMT) has certainly reached a tipping point. The surge in interest in FMT among physicians and researchers over the past 2-3 years is evident by increasing numbers of publications and registered clinical trials. The lay press is full of stories of lives saved by fecal transplant. There are guidebooks for patients, online resources such as "The Power of Poop," and even YouTube videos describing "do it yourself" FMT.

It’s a rather simple procedure: identify a donor, process the stool, and administer it to the patient. However, each of these steps has generated many questions and some debate and there is currently no standard FMT protocol. Indeed, the optimum methods may vary depending on the clinical situation. The evidence is mounting in support of FMT for recurrent C. difficile infection (r- CDI). A recent systematic review of over 500 patients (J. Clin. Gastroenterol. 2014. epub Jan 2014) showed that 87% experienced clinical resolution after FMT with no serious adverse events reported. The first randomized controlled trial, published last year, (N. Engl. J. Med. 2013;368:407-15) confirmed the safety and efficacy of FMT for r-CDI. The data are growing on the mechanisms of effect. A recent study of 14 patients treated with FMT showed that, prior to FMT, these patients lacked the gut microbial diversity seen in their donors (PLoS One 2013;8:e81330). Post-FMT, they became more similar to their donors, with increased diversity, increased numbers of butyrate-producing organisms, and decreased Proteobacteria.

Despite good efficacy, ease of administration, and the lack of therapeutic alternatives for many patients, there are challenges to widespread implementation. Though FMT appears safe, prospective data are lacking. There have been case reports of fevers, bacteremia, and inflammatory bowel disease flares after FMT and theoretical concerns exist about transmitting risk factors for other conditions associated with dysbiosis, such as obesity and autoimmune disease. Many patients have difficulty identifying a healthy donor, screening protocols may be cumbersome, and long turn-around time in donor screening and laboratory testing limits use in emergent cases. Furthermore, relying on the availability of fresh material to treat patients presents obvious logistical difficulties. In terms of reimbursement, questions remain about who should pay for donor screening (donor vs. recipient insurance), how to bill for FMT delivery, and whether some insurers will pay given that most consider it an experimental procedure.

The regulatory landscape is rapidly evolving. The Food and Drug Administration announced at a public workshop last May that an investigational new drug application (IND) was required in order to treat patients with FMT. The IND process presents a large administrative burden to the average practitioner as INDs must include a detailed protocol, safety monitoring, and reporting plans, and annual reports. After outcry from patients and providers, the agency amended this policy and determined it would exercise "enforcement discretion." Providers would be permitted to administer FMT to individual patients with CDI not responding to standard therapies as long as they provide informed consent stating that FMT is investigational and discuss potential risks.

In the near future, physicians will not have to identify donors or rely on fresh stool to perform FMT. Stool banks, such as OpenBiome, have centralized donor screening and stool processing and hope to supply physicians with material to treat patients and researchers conducting clinical trials on applications of FMT. Commercialized preparations of minimally modified stool (which would be stored and shipped to providers when needed) are in clinical trials. Defined microbiota ecosystems, in which the species responsible for therapeutic effects are isolated and delivered, have been effective in animal and human trials. Ultimately, encapsulated formulations would be the easiest delivery method and enable thousands of patients to be treated, perhaps earlier in the course of disease. Dr. Thomas Louie at the University of Calgary reported successfully treating 27 patients with orally administered capsules containing fresh donor stool. Seres Health (Cambridge, Mass.) has developed an encapsulated formulation comprised of the "essential organisms" found in FMT. This product is currently in clinical trials, and efficacy has been observed in doses greater than 10,000-fold below the bacterial dose given in a conventional FMT.

In conclusion, there is good evidence supporting FMT for treatment of r-CDI and we are beginning to understand the mechanisms of therapeutic effect. Challenges remain and regulation is necessary, though agencies must recognize the unique nature of FMT and adapt policies as microbial therapeutics emerges.

Dr. Kelly, FACG, is assistant professor of medicine, Alpert School of Medicine, Brown University, Providence, R.I. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Though previously considered fringe medicine and the "last resort" for patients with Clostridium difficile infection, fecal microbiota transplantation (FMT) has certainly reached a tipping point. The surge in interest in FMT among physicians and researchers over the past 2-3 years is evident by increasing numbers of publications and registered clinical trials. The lay press is full of stories of lives saved by fecal transplant. There are guidebooks for patients, online resources such as "The Power of Poop," and even YouTube videos describing "do it yourself" FMT.

It’s a rather simple procedure: identify a donor, process the stool, and administer it to the patient. However, each of these steps has generated many questions and some debate and there is currently no standard FMT protocol. Indeed, the optimum methods may vary depending on the clinical situation. The evidence is mounting in support of FMT for recurrent C. difficile infection (r- CDI). A recent systematic review of over 500 patients (J. Clin. Gastroenterol. 2014. epub Jan 2014) showed that 87% experienced clinical resolution after FMT with no serious adverse events reported. The first randomized controlled trial, published last year, (N. Engl. J. Med. 2013;368:407-15) confirmed the safety and efficacy of FMT for r-CDI. The data are growing on the mechanisms of effect. A recent study of 14 patients treated with FMT showed that, prior to FMT, these patients lacked the gut microbial diversity seen in their donors (PLoS One 2013;8:e81330). Post-FMT, they became more similar to their donors, with increased diversity, increased numbers of butyrate-producing organisms, and decreased Proteobacteria.

Despite good efficacy, ease of administration, and the lack of therapeutic alternatives for many patients, there are challenges to widespread implementation. Though FMT appears safe, prospective data are lacking. There have been case reports of fevers, bacteremia, and inflammatory bowel disease flares after FMT and theoretical concerns exist about transmitting risk factors for other conditions associated with dysbiosis, such as obesity and autoimmune disease. Many patients have difficulty identifying a healthy donor, screening protocols may be cumbersome, and long turn-around time in donor screening and laboratory testing limits use in emergent cases. Furthermore, relying on the availability of fresh material to treat patients presents obvious logistical difficulties. In terms of reimbursement, questions remain about who should pay for donor screening (donor vs. recipient insurance), how to bill for FMT delivery, and whether some insurers will pay given that most consider it an experimental procedure.

The regulatory landscape is rapidly evolving. The Food and Drug Administration announced at a public workshop last May that an investigational new drug application (IND) was required in order to treat patients with FMT. The IND process presents a large administrative burden to the average practitioner as INDs must include a detailed protocol, safety monitoring, and reporting plans, and annual reports. After outcry from patients and providers, the agency amended this policy and determined it would exercise "enforcement discretion." Providers would be permitted to administer FMT to individual patients with CDI not responding to standard therapies as long as they provide informed consent stating that FMT is investigational and discuss potential risks.

In the near future, physicians will not have to identify donors or rely on fresh stool to perform FMT. Stool banks, such as OpenBiome, have centralized donor screening and stool processing and hope to supply physicians with material to treat patients and researchers conducting clinical trials on applications of FMT. Commercialized preparations of minimally modified stool (which would be stored and shipped to providers when needed) are in clinical trials. Defined microbiota ecosystems, in which the species responsible for therapeutic effects are isolated and delivered, have been effective in animal and human trials. Ultimately, encapsulated formulations would be the easiest delivery method and enable thousands of patients to be treated, perhaps earlier in the course of disease. Dr. Thomas Louie at the University of Calgary reported successfully treating 27 patients with orally administered capsules containing fresh donor stool. Seres Health (Cambridge, Mass.) has developed an encapsulated formulation comprised of the "essential organisms" found in FMT. This product is currently in clinical trials, and efficacy has been observed in doses greater than 10,000-fold below the bacterial dose given in a conventional FMT.

In conclusion, there is good evidence supporting FMT for treatment of r-CDI and we are beginning to understand the mechanisms of therapeutic effect. Challenges remain and regulation is necessary, though agencies must recognize the unique nature of FMT and adapt policies as microbial therapeutics emerges.

Dr. Kelly, FACG, is assistant professor of medicine, Alpert School of Medicine, Brown University, Providence, R.I. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Though previously considered fringe medicine and the "last resort" for patients with Clostridium difficile infection, fecal microbiota transplantation (FMT) has certainly reached a tipping point. The surge in interest in FMT among physicians and researchers over the past 2-3 years is evident by increasing numbers of publications and registered clinical trials. The lay press is full of stories of lives saved by fecal transplant. There are guidebooks for patients, online resources such as "The Power of Poop," and even YouTube videos describing "do it yourself" FMT.

It’s a rather simple procedure: identify a donor, process the stool, and administer it to the patient. However, each of these steps has generated many questions and some debate and there is currently no standard FMT protocol. Indeed, the optimum methods may vary depending on the clinical situation. The evidence is mounting in support of FMT for recurrent C. difficile infection (r- CDI). A recent systematic review of over 500 patients (J. Clin. Gastroenterol. 2014. epub Jan 2014) showed that 87% experienced clinical resolution after FMT with no serious adverse events reported. The first randomized controlled trial, published last year, (N. Engl. J. Med. 2013;368:407-15) confirmed the safety and efficacy of FMT for r-CDI. The data are growing on the mechanisms of effect. A recent study of 14 patients treated with FMT showed that, prior to FMT, these patients lacked the gut microbial diversity seen in their donors (PLoS One 2013;8:e81330). Post-FMT, they became more similar to their donors, with increased diversity, increased numbers of butyrate-producing organisms, and decreased Proteobacteria.

Despite good efficacy, ease of administration, and the lack of therapeutic alternatives for many patients, there are challenges to widespread implementation. Though FMT appears safe, prospective data are lacking. There have been case reports of fevers, bacteremia, and inflammatory bowel disease flares after FMT and theoretical concerns exist about transmitting risk factors for other conditions associated with dysbiosis, such as obesity and autoimmune disease. Many patients have difficulty identifying a healthy donor, screening protocols may be cumbersome, and long turn-around time in donor screening and laboratory testing limits use in emergent cases. Furthermore, relying on the availability of fresh material to treat patients presents obvious logistical difficulties. In terms of reimbursement, questions remain about who should pay for donor screening (donor vs. recipient insurance), how to bill for FMT delivery, and whether some insurers will pay given that most consider it an experimental procedure.

The regulatory landscape is rapidly evolving. The Food and Drug Administration announced at a public workshop last May that an investigational new drug application (IND) was required in order to treat patients with FMT. The IND process presents a large administrative burden to the average practitioner as INDs must include a detailed protocol, safety monitoring, and reporting plans, and annual reports. After outcry from patients and providers, the agency amended this policy and determined it would exercise "enforcement discretion." Providers would be permitted to administer FMT to individual patients with CDI not responding to standard therapies as long as they provide informed consent stating that FMT is investigational and discuss potential risks.

In the near future, physicians will not have to identify donors or rely on fresh stool to perform FMT. Stool banks, such as OpenBiome, have centralized donor screening and stool processing and hope to supply physicians with material to treat patients and researchers conducting clinical trials on applications of FMT. Commercialized preparations of minimally modified stool (which would be stored and shipped to providers when needed) are in clinical trials. Defined microbiota ecosystems, in which the species responsible for therapeutic effects are isolated and delivered, have been effective in animal and human trials. Ultimately, encapsulated formulations would be the easiest delivery method and enable thousands of patients to be treated, perhaps earlier in the course of disease. Dr. Thomas Louie at the University of Calgary reported successfully treating 27 patients with orally administered capsules containing fresh donor stool. Seres Health (Cambridge, Mass.) has developed an encapsulated formulation comprised of the "essential organisms" found in FMT. This product is currently in clinical trials, and efficacy has been observed in doses greater than 10,000-fold below the bacterial dose given in a conventional FMT.

In conclusion, there is good evidence supporting FMT for treatment of r-CDI and we are beginning to understand the mechanisms of therapeutic effect. Challenges remain and regulation is necessary, though agencies must recognize the unique nature of FMT and adapt policies as microbial therapeutics emerges.

Dr. Kelly, FACG, is assistant professor of medicine, Alpert School of Medicine, Brown University, Providence, R.I. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.