TBD Meeting (5815-15)

ORLANDO – You think in terms of inflammation, but your inflammatory bowel disease patients tend to think in terms of clinical symptoms, often unilaterally changing their diets according to how they “feel,” rather than in relation to their disease activity, despite your reassurances that diet is not causal to their disease state.

“The data on IBD and diet are awfully thin,” Dr. Peter D.R. Higgins, who directs the IBD program at the University of Michigan, Ann Arbor, said at a conference on inflammatory bowel diseases. The result of this data dearth is that clinicians “have a credibility gap when it comes to diet and IBD,” he said.

Although diet can be manipulated to reduce antigens, toxins, and other aggravating elements, as well as to alter gut bacteria composition, gas, and fluid retention – all possible, even “sensible” mechanisms for some symptoms, according to Dr. Higgins – there still is not enough evidence to link them to disease activity.

Any studies that show a modicum of relationship between diet and IBD currently are still bench science. Of the 11 clinical, randomized, controlled trials Dr. Higgins said he reviewed, none were positive studies. “Zero.”

That goes for exclusive enteral nutrition, too. “There are zero prospective randomized, controlled trials for mucosal healing endpoints for EEN. None,” said Dr. Higgins.

To accrue such data is difficult for many reasons, Dr. Higgins said, especially because extremely large sample sizes are needed, a Herculean feat since so many IBD patients have very decided opinions about diet and would balk at being randomly assigned to certain test groups, and because to blind them as to what they were eating would be difficult. “You need a convincing sham diet that is identical to the intervention diet in every way.” He said there are similar concerns for testing nutriceuticals.

Meanwhile, patients desperate to assuage symptoms such as bloating and abdominal pressure thus go rogue, severely restricting their diets, spending money on alternative therapies, and even discontinuing their prescribed anti-inflammatories per the counsel of so-called Internet gurus whose primary directive is, according to Dr. Higgins, “to denigrate Western medicine.

Very often, IBD patients will develop food avoidances, usually dairy, gluten, fiber, nuts, and some meats, Dr. Higgins said, citing a poster presented at the meeting. Patients with Crohn’s disease or ulcerative colitis reported that they believed certain foods exacerbated their symptoms, so they cut them from their diets. Over time, this leads to malnutrition, including a depletion of micronutrients, he noted.

One study showed that 7% of inpatients with IBD met criteria for severe protein and calorie malnutrition, which was associated with more than triple mortality rates for this cohort, as well as double the length of stays and at twice the cost.

“Patients who choose to do this make their outcomes a lot worse,” Dr. Higgins said. “We really need to prevent [patients from inflicting] self-harm.”

The way forward is to engage patients on diet, and keep them talking.

“Reassure them that you are paying attention to their nutrition, and test them regularly for low iron, low vitamin D, and vitamin B₁₂. Reassure them when [the levels] are normal, and supplement them when deficient,” Dr. Higgins said.

There’s just not enough evidence for offering more treatment than that, aside from patients making sure to meet their protein and caloric needs, according to Dr. Higgins. For patients on methotrexate or sulfasalazine, “you could also recommend folate,” he said.

To facilitate conversations about diet and IBD with patients, Dr. Higgins said he does rely on one “terrible study” that had no controls, no randomization, and only retrospective patient assessment of symptoms, but which correlated a low FODMAP (fermentable oligo-, di-, monosaccharides and polyols) diet with lower rates of abdominal pain, bloating, gas, and diarrhea in half of the 52 Crohn’s and 20 ulcerative colitis patients who participated. There was no change in levels of inflammation, however.

“It’s basically a case series, but at least there is no evidence of harm, and it allows me to regain credibility and recapture the patient from the [online] Rasputins,” Dr. Higgins said.

He offered this strategy: Engage patients by talking about and treating their IBD symptoms, so you can get them to work with you when you have concerns around any disease activity. If you think a patient would benefit from a low FODMAP diet, try it. Typical candidates for this approach, he said, are those who have a small intestine bacterial overgrowth response to antibiotics, and those with a history of abdominal pain, distension, extreme amounts of gas, strictures, adhesions, slow motility, and those lacking an ileocecal valve.

If a patient experiences a flare, restricting the diet does make sense in terms of reducing discomfort, Dr. Higgins said, but these patients run the risk of “dehydration, and rapid and significant malnutrition” if they continue to restrict their diets once the flare has quieted.

To lessen symptoms during a flare, patients can be counseled to eat smaller quantities of food, to eat bland food, and to steer clear of caffeine and alcohol, the former making motility worse, and the latter increasing dehydration.

Patients seeking to alleviate symptoms can benefit from “low residue” diets that are low in fiber. Overall, stress the importance of protein and caloric intake, even recommending that patients take liquid calorie supplements if necessary, particularly when sick.

To deepen and continue this kind of patient interaction in your clinic, Dr. Higgins said it is increasingly possible to find a balance between patient volume and interest in this model, registered dietitians – preferably those who can see patients on site, and third-party payers who will cover these services.

The meeting was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Higgins has numerous financial relationships with pharmaceutical companies, including Abbott, Buhlman, Centocor, Millenium, and Pfizer.

[email protected]

On Twitter @whitneymcknight

ORLANDO – You think in terms of inflammation, but your inflammatory bowel disease patients tend to think in terms of clinical symptoms, often unilaterally changing their diets according to how they “feel,” rather than in relation to their disease activity, despite your reassurances that diet is not causal to their disease state.

“The data on IBD and diet are awfully thin,” Dr. Peter D.R. Higgins, who directs the IBD program at the University of Michigan, Ann Arbor, said at a conference on inflammatory bowel diseases. The result of this data dearth is that clinicians “have a credibility gap when it comes to diet and IBD,” he said.

Although diet can be manipulated to reduce antigens, toxins, and other aggravating elements, as well as to alter gut bacteria composition, gas, and fluid retention – all possible, even “sensible” mechanisms for some symptoms, according to Dr. Higgins – there still is not enough evidence to link them to disease activity.

Any studies that show a modicum of relationship between diet and IBD currently are still bench science. Of the 11 clinical, randomized, controlled trials Dr. Higgins said he reviewed, none were positive studies. “Zero.”

That goes for exclusive enteral nutrition, too. “There are zero prospective randomized, controlled trials for mucosal healing endpoints for EEN. None,” said Dr. Higgins.

To accrue such data is difficult for many reasons, Dr. Higgins said, especially because extremely large sample sizes are needed, a Herculean feat since so many IBD patients have very decided opinions about diet and would balk at being randomly assigned to certain test groups, and because to blind them as to what they were eating would be difficult. “You need a convincing sham diet that is identical to the intervention diet in every way.” He said there are similar concerns for testing nutriceuticals.

Meanwhile, patients desperate to assuage symptoms such as bloating and abdominal pressure thus go rogue, severely restricting their diets, spending money on alternative therapies, and even discontinuing their prescribed anti-inflammatories per the counsel of so-called Internet gurus whose primary directive is, according to Dr. Higgins, “to denigrate Western medicine.

Very often, IBD patients will develop food avoidances, usually dairy, gluten, fiber, nuts, and some meats, Dr. Higgins said, citing a poster presented at the meeting. Patients with Crohn’s disease or ulcerative colitis reported that they believed certain foods exacerbated their symptoms, so they cut them from their diets. Over time, this leads to malnutrition, including a depletion of micronutrients, he noted.

One study showed that 7% of inpatients with IBD met criteria for severe protein and calorie malnutrition, which was associated with more than triple mortality rates for this cohort, as well as double the length of stays and at twice the cost.

“Patients who choose to do this make their outcomes a lot worse,” Dr. Higgins said. “We really need to prevent [patients from inflicting] self-harm.”

The way forward is to engage patients on diet, and keep them talking.

“Reassure them that you are paying attention to their nutrition, and test them regularly for low iron, low vitamin D, and vitamin B₁₂. Reassure them when [the levels] are normal, and supplement them when deficient,” Dr. Higgins said.

There’s just not enough evidence for offering more treatment than that, aside from patients making sure to meet their protein and caloric needs, according to Dr. Higgins. For patients on methotrexate or sulfasalazine, “you could also recommend folate,” he said.

To facilitate conversations about diet and IBD with patients, Dr. Higgins said he does rely on one “terrible study” that had no controls, no randomization, and only retrospective patient assessment of symptoms, but which correlated a low FODMAP (fermentable oligo-, di-, monosaccharides and polyols) diet with lower rates of abdominal pain, bloating, gas, and diarrhea in half of the 52 Crohn’s and 20 ulcerative colitis patients who participated. There was no change in levels of inflammation, however.

“It’s basically a case series, but at least there is no evidence of harm, and it allows me to regain credibility and recapture the patient from the [online] Rasputins,” Dr. Higgins said.

He offered this strategy: Engage patients by talking about and treating their IBD symptoms, so you can get them to work with you when you have concerns around any disease activity. If you think a patient would benefit from a low FODMAP diet, try it. Typical candidates for this approach, he said, are those who have a small intestine bacterial overgrowth response to antibiotics, and those with a history of abdominal pain, distension, extreme amounts of gas, strictures, adhesions, slow motility, and those lacking an ileocecal valve.

If a patient experiences a flare, restricting the diet does make sense in terms of reducing discomfort, Dr. Higgins said, but these patients run the risk of “dehydration, and rapid and significant malnutrition” if they continue to restrict their diets once the flare has quieted.

To lessen symptoms during a flare, patients can be counseled to eat smaller quantities of food, to eat bland food, and to steer clear of caffeine and alcohol, the former making motility worse, and the latter increasing dehydration.

Patients seeking to alleviate symptoms can benefit from “low residue” diets that are low in fiber. Overall, stress the importance of protein and caloric intake, even recommending that patients take liquid calorie supplements if necessary, particularly when sick.

To deepen and continue this kind of patient interaction in your clinic, Dr. Higgins said it is increasingly possible to find a balance between patient volume and interest in this model, registered dietitians – preferably those who can see patients on site, and third-party payers who will cover these services.

The meeting was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Higgins has numerous financial relationships with pharmaceutical companies, including Abbott, Buhlman, Centocor, Millenium, and Pfizer.

[email protected]

On Twitter @whitneymcknight

ORLANDO – You think in terms of inflammation, but your inflammatory bowel disease patients tend to think in terms of clinical symptoms, often unilaterally changing their diets according to how they “feel,” rather than in relation to their disease activity, despite your reassurances that diet is not causal to their disease state.

“The data on IBD and diet are awfully thin,” Dr. Peter D.R. Higgins, who directs the IBD program at the University of Michigan, Ann Arbor, said at a conference on inflammatory bowel diseases. The result of this data dearth is that clinicians “have a credibility gap when it comes to diet and IBD,” he said.

Although diet can be manipulated to reduce antigens, toxins, and other aggravating elements, as well as to alter gut bacteria composition, gas, and fluid retention – all possible, even “sensible” mechanisms for some symptoms, according to Dr. Higgins – there still is not enough evidence to link them to disease activity.

Any studies that show a modicum of relationship between diet and IBD currently are still bench science. Of the 11 clinical, randomized, controlled trials Dr. Higgins said he reviewed, none were positive studies. “Zero.”

That goes for exclusive enteral nutrition, too. “There are zero prospective randomized, controlled trials for mucosal healing endpoints for EEN. None,” said Dr. Higgins.

To accrue such data is difficult for many reasons, Dr. Higgins said, especially because extremely large sample sizes are needed, a Herculean feat since so many IBD patients have very decided opinions about diet and would balk at being randomly assigned to certain test groups, and because to blind them as to what they were eating would be difficult. “You need a convincing sham diet that is identical to the intervention diet in every way.” He said there are similar concerns for testing nutriceuticals.

Meanwhile, patients desperate to assuage symptoms such as bloating and abdominal pressure thus go rogue, severely restricting their diets, spending money on alternative therapies, and even discontinuing their prescribed anti-inflammatories per the counsel of so-called Internet gurus whose primary directive is, according to Dr. Higgins, “to denigrate Western medicine.

Very often, IBD patients will develop food avoidances, usually dairy, gluten, fiber, nuts, and some meats, Dr. Higgins said, citing a poster presented at the meeting. Patients with Crohn’s disease or ulcerative colitis reported that they believed certain foods exacerbated their symptoms, so they cut them from their diets. Over time, this leads to malnutrition, including a depletion of micronutrients, he noted.

One study showed that 7% of inpatients with IBD met criteria for severe protein and calorie malnutrition, which was associated with more than triple mortality rates for this cohort, as well as double the length of stays and at twice the cost.

“Patients who choose to do this make their outcomes a lot worse,” Dr. Higgins said. “We really need to prevent [patients from inflicting] self-harm.”

The way forward is to engage patients on diet, and keep them talking.

“Reassure them that you are paying attention to their nutrition, and test them regularly for low iron, low vitamin D, and vitamin B₁₂. Reassure them when [the levels] are normal, and supplement them when deficient,” Dr. Higgins said.

There’s just not enough evidence for offering more treatment than that, aside from patients making sure to meet their protein and caloric needs, according to Dr. Higgins. For patients on methotrexate or sulfasalazine, “you could also recommend folate,” he said.

To facilitate conversations about diet and IBD with patients, Dr. Higgins said he does rely on one “terrible study” that had no controls, no randomization, and only retrospective patient assessment of symptoms, but which correlated a low FODMAP (fermentable oligo-, di-, monosaccharides and polyols) diet with lower rates of abdominal pain, bloating, gas, and diarrhea in half of the 52 Crohn’s and 20 ulcerative colitis patients who participated. There was no change in levels of inflammation, however.

“It’s basically a case series, but at least there is no evidence of harm, and it allows me to regain credibility and recapture the patient from the [online] Rasputins,” Dr. Higgins said.

He offered this strategy: Engage patients by talking about and treating their IBD symptoms, so you can get them to work with you when you have concerns around any disease activity. If you think a patient would benefit from a low FODMAP diet, try it. Typical candidates for this approach, he said, are those who have a small intestine bacterial overgrowth response to antibiotics, and those with a history of abdominal pain, distension, extreme amounts of gas, strictures, adhesions, slow motility, and those lacking an ileocecal valve.

If a patient experiences a flare, restricting the diet does make sense in terms of reducing discomfort, Dr. Higgins said, but these patients run the risk of “dehydration, and rapid and significant malnutrition” if they continue to restrict their diets once the flare has quieted.

To lessen symptoms during a flare, patients can be counseled to eat smaller quantities of food, to eat bland food, and to steer clear of caffeine and alcohol, the former making motility worse, and the latter increasing dehydration.

Patients seeking to alleviate symptoms can benefit from “low residue” diets that are low in fiber. Overall, stress the importance of protein and caloric intake, even recommending that patients take liquid calorie supplements if necessary, particularly when sick.

To deepen and continue this kind of patient interaction in your clinic, Dr. Higgins said it is increasingly possible to find a balance between patient volume and interest in this model, registered dietitians – preferably those who can see patients on site, and third-party payers who will cover these services.

The meeting was sponsored by the Crohn’s & Colitis Foundation of America. Dr. Higgins has numerous financial relationships with pharmaceutical companies, including Abbott, Buhlman, Centocor, Millenium, and Pfizer.

[email protected]

On Twitter @whitneymcknight

ORLANDO– Independent investigators eager to author studies that have notable impact on the field of inflammatory bowel disease have plenty of important paths to pursue, according to Dr. Jean-Frederic Colombel, a professor of gastroenterology at Mt. Sinai Hospital in New York.

“Over the next 3-5 years, we will have a lot of new drugs, which is nice, but we don’t yet know how to use them, or which ones to use,” Dr. Colombel said during a presentation on the future of the field at this year’s meeting of the annual Advances in Inflammatory Bowel Disease, sponsored by the Crohn’s and Colitis Foundation of America and endorsed by the American Gastroenterological Association.

Whitney McKnight/Frontline Medical Media

A host of biologics including vedolizumab, recently indicated by the U.S. Food and Drug Administration for ulcerative colitis and Crohn’s disease, and ustekinumab, currently in phase III studies for Crohn’s disease, are set to revolutionize treatment at a time when the field is already undergoing great change, according to Dr. Colombel. The result, he says, is that despite “formidable” challenges in recruitment and funding, “huge opportunities” exist for investigators willing to collaborate and be creative.

Studies that elucidate the natural history of Crohn’s disease and colitis offer insight into the efficacy of various treatment strategies, help determine whether to target symptoms or biomarkers, and answer whether combination therapies are safe and effective in certain patients are what Dr. Colombel says he hopes will help improve the field as the drug pipeline continues to grow.

He stipulated a caveat, however, “I strongly believe we need some new study designs.” Although he noted that trials needn’t be complicated, they should be long enough to collect sorely needed prospective data. “These can only be done in investigator-initiated trials because of the time frames,” Dr. Colombel urged the audience of young investigators.

A fieldwide shift in thinking about ulcerative colitis and Crohn’s disease as chronic, progressive diseases, rather than intermittent afflictions has already helped generate new study endpoints such as the Lémann Score, an index of progressive bowel damage that allows researchers to better track the history of IBD in patients, and thus provide a window of opportunity for interventions, said Dr. Colombel.

To wit, the CURE study, conducted by the French IBD society GITAID, is a 5-year, prospective study of patients whose early Crohn’s disease is treated with the biologic adalimumab. The Lémann Score is used to screen patients at the end of each successive year, in order to adjust their treatment to reach the final endpoint of deep remission by year 5 when several indicators are measured, including bowel image, level of disability, and whether there was the need for surgery. Dr. Colombel said the novel design of the study, which has already recruited 60 patients, shows it is “feasible” to collect longitudinal data.

The field also has a responsibility to conduct randomly assigned controlled trials to demonstrate the comparative effectiveness, safety, immunogenicity, and cost benefits of the rapidly emerging spate of biosimilars, particularly since there is not global agreement about their use, according to Dr. Colombel. Their approval for IBD in Europe is “highly disputable.... I think this could be a very nice topic for an investigator-initiated trial, in Canada and the U.S.”

Head-to-head trials that are well designed will help answer “very important questions” about which treatment strategies have the best outcomes, but doing so requires fortitude, according to Dr. Colombel. “The Dutch have the guts to conduct the LIRIC trial,” he said. In it, patients with Crohn’s disease in the terminal ileum, who have failed steroids or immune therapy, will be assigned randomly to either laparoscopic ileocolic resection or infliximab, the first available biosimilar. Sixty participants have enrolled to date, he said.

These types of studies could also help delineate how best to employ combination therapies. “What I propose for this kind of study is an intensive therapy combining biologics very early in patients with bad prognoses, and looking at the long-term outcome using bowel image,” Dr. Colombel said. These data, and others indicating the most appropriate length of treatment in patients with varying states of disease, are Dr. Colombel’s personal “top choice” for investigation. The excitement that personalized medicine has engendered across the specialities has so far not resulted in specific, validated treatments for IBD patients. However, the question of how to use personal characteristics and serologic and genetic markers to create predictive models for which patients will need either step-up or top-down therapies, accounting for their individual risk of complication, is what he said is among the most “important [question] we need to answer because the choice of early therapy will depend on this predictor,” according to Dr. Colombel.

The question of which treatment targets are best remains unclear but is important to decipher, according to Dr. Colombel, who said simple studies comparing outcomes when patients are treated to symptoms vs. treated to biomarker measurements are needed, as well as the importance of mucosal healing vs. symptom improvement. “This is important because there is discordance between endoscopy and histology,” said Dr. Colombel. “Persistent histologic inflammation is frequently associated with bad outcomes.”

However, endoscopic scoring itself is another area Dr. Colombel said is worth investigating, especially when it comes to validating endpoints such as those in the Crohn’s Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn’s Disease (SES-CD), which will help determine remission cutoffs. Also, endoscopic scoring in comparison with live video and imaging still need standardized approaches. “When you see how it is done in the U.S., it is generally very poor,” Dr. Colombel said.

The biggest obstacles of all when it comes to independent investigation in the United States, according to Frenchman Dr. Colombel, is heavy regulation and cost. “In France, [conducting trials] was considered part of my job. I was not compensated. It is different here.”

Dr. Colombel has numerous financial ties to the pharmaceutical industry, including AB Science, Amgen, Baxter, Bristol-Meyers Squibb, and Merck, among several others.

[email protected]


On Twitter @whitneymcknight

ORLANDO– Independent investigators eager to author studies that have notable impact on the field of inflammatory bowel disease have plenty of important paths to pursue, according to Dr. Jean-Frederic Colombel, a professor of gastroenterology at Mt. Sinai Hospital in New York.

“Over the next 3-5 years, we will have a lot of new drugs, which is nice, but we don’t yet know how to use them, or which ones to use,” Dr. Colombel said during a presentation on the future of the field at this year’s meeting of the annual Advances in Inflammatory Bowel Disease, sponsored by the Crohn’s and Colitis Foundation of America and endorsed by the American Gastroenterological Association.

Whitney McKnight/Frontline Medical Media

A host of biologics including vedolizumab, recently indicated by the U.S. Food and Drug Administration for ulcerative colitis and Crohn’s disease, and ustekinumab, currently in phase III studies for Crohn’s disease, are set to revolutionize treatment at a time when the field is already undergoing great change, according to Dr. Colombel. The result, he says, is that despite “formidable” challenges in recruitment and funding, “huge opportunities” exist for investigators willing to collaborate and be creative.

Studies that elucidate the natural history of Crohn’s disease and colitis offer insight into the efficacy of various treatment strategies, help determine whether to target symptoms or biomarkers, and answer whether combination therapies are safe and effective in certain patients are what Dr. Colombel says he hopes will help improve the field as the drug pipeline continues to grow.

He stipulated a caveat, however, “I strongly believe we need some new study designs.” Although he noted that trials needn’t be complicated, they should be long enough to collect sorely needed prospective data. “These can only be done in investigator-initiated trials because of the time frames,” Dr. Colombel urged the audience of young investigators.

A fieldwide shift in thinking about ulcerative colitis and Crohn’s disease as chronic, progressive diseases, rather than intermittent afflictions has already helped generate new study endpoints such as the Lémann Score, an index of progressive bowel damage that allows researchers to better track the history of IBD in patients, and thus provide a window of opportunity for interventions, said Dr. Colombel.

To wit, the CURE study, conducted by the French IBD society GITAID, is a 5-year, prospective study of patients whose early Crohn’s disease is treated with the biologic adalimumab. The Lémann Score is used to screen patients at the end of each successive year, in order to adjust their treatment to reach the final endpoint of deep remission by year 5 when several indicators are measured, including bowel image, level of disability, and whether there was the need for surgery. Dr. Colombel said the novel design of the study, which has already recruited 60 patients, shows it is “feasible” to collect longitudinal data.

The field also has a responsibility to conduct randomly assigned controlled trials to demonstrate the comparative effectiveness, safety, immunogenicity, and cost benefits of the rapidly emerging spate of biosimilars, particularly since there is not global agreement about their use, according to Dr. Colombel. Their approval for IBD in Europe is “highly disputable.... I think this could be a very nice topic for an investigator-initiated trial, in Canada and the U.S.”

Head-to-head trials that are well designed will help answer “very important questions” about which treatment strategies have the best outcomes, but doing so requires fortitude, according to Dr. Colombel. “The Dutch have the guts to conduct the LIRIC trial,” he said. In it, patients with Crohn’s disease in the terminal ileum, who have failed steroids or immune therapy, will be assigned randomly to either laparoscopic ileocolic resection or infliximab, the first available biosimilar. Sixty participants have enrolled to date, he said.

These types of studies could also help delineate how best to employ combination therapies. “What I propose for this kind of study is an intensive therapy combining biologics very early in patients with bad prognoses, and looking at the long-term outcome using bowel image,” Dr. Colombel said. These data, and others indicating the most appropriate length of treatment in patients with varying states of disease, are Dr. Colombel’s personal “top choice” for investigation. The excitement that personalized medicine has engendered across the specialities has so far not resulted in specific, validated treatments for IBD patients. However, the question of how to use personal characteristics and serologic and genetic markers to create predictive models for which patients will need either step-up or top-down therapies, accounting for their individual risk of complication, is what he said is among the most “important [question] we need to answer because the choice of early therapy will depend on this predictor,” according to Dr. Colombel.

The question of which treatment targets are best remains unclear but is important to decipher, according to Dr. Colombel, who said simple studies comparing outcomes when patients are treated to symptoms vs. treated to biomarker measurements are needed, as well as the importance of mucosal healing vs. symptom improvement. “This is important because there is discordance between endoscopy and histology,” said Dr. Colombel. “Persistent histologic inflammation is frequently associated with bad outcomes.”

However, endoscopic scoring itself is another area Dr. Colombel said is worth investigating, especially when it comes to validating endpoints such as those in the Crohn’s Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn’s Disease (SES-CD), which will help determine remission cutoffs. Also, endoscopic scoring in comparison with live video and imaging still need standardized approaches. “When you see how it is done in the U.S., it is generally very poor,” Dr. Colombel said.

The biggest obstacles of all when it comes to independent investigation in the United States, according to Frenchman Dr. Colombel, is heavy regulation and cost. “In France, [conducting trials] was considered part of my job. I was not compensated. It is different here.”

Dr. Colombel has numerous financial ties to the pharmaceutical industry, including AB Science, Amgen, Baxter, Bristol-Meyers Squibb, and Merck, among several others.

[email protected]


On Twitter @whitneymcknight

ORLANDO– Independent investigators eager to author studies that have notable impact on the field of inflammatory bowel disease have plenty of important paths to pursue, according to Dr. Jean-Frederic Colombel, a professor of gastroenterology at Mt. Sinai Hospital in New York.

“Over the next 3-5 years, we will have a lot of new drugs, which is nice, but we don’t yet know how to use them, or which ones to use,” Dr. Colombel said during a presentation on the future of the field at this year’s meeting of the annual Advances in Inflammatory Bowel Disease, sponsored by the Crohn’s and Colitis Foundation of America and endorsed by the American Gastroenterological Association.

Whitney McKnight/Frontline Medical Media

A host of biologics including vedolizumab, recently indicated by the U.S. Food and Drug Administration for ulcerative colitis and Crohn’s disease, and ustekinumab, currently in phase III studies for Crohn’s disease, are set to revolutionize treatment at a time when the field is already undergoing great change, according to Dr. Colombel. The result, he says, is that despite “formidable” challenges in recruitment and funding, “huge opportunities” exist for investigators willing to collaborate and be creative.

Studies that elucidate the natural history of Crohn’s disease and colitis offer insight into the efficacy of various treatment strategies, help determine whether to target symptoms or biomarkers, and answer whether combination therapies are safe and effective in certain patients are what Dr. Colombel says he hopes will help improve the field as the drug pipeline continues to grow.

He stipulated a caveat, however, “I strongly believe we need some new study designs.” Although he noted that trials needn’t be complicated, they should be long enough to collect sorely needed prospective data. “These can only be done in investigator-initiated trials because of the time frames,” Dr. Colombel urged the audience of young investigators.

A fieldwide shift in thinking about ulcerative colitis and Crohn’s disease as chronic, progressive diseases, rather than intermittent afflictions has already helped generate new study endpoints such as the Lémann Score, an index of progressive bowel damage that allows researchers to better track the history of IBD in patients, and thus provide a window of opportunity for interventions, said Dr. Colombel.

To wit, the CURE study, conducted by the French IBD society GITAID, is a 5-year, prospective study of patients whose early Crohn’s disease is treated with the biologic adalimumab. The Lémann Score is used to screen patients at the end of each successive year, in order to adjust their treatment to reach the final endpoint of deep remission by year 5 when several indicators are measured, including bowel image, level of disability, and whether there was the need for surgery. Dr. Colombel said the novel design of the study, which has already recruited 60 patients, shows it is “feasible” to collect longitudinal data.

The field also has a responsibility to conduct randomly assigned controlled trials to demonstrate the comparative effectiveness, safety, immunogenicity, and cost benefits of the rapidly emerging spate of biosimilars, particularly since there is not global agreement about their use, according to Dr. Colombel. Their approval for IBD in Europe is “highly disputable.... I think this could be a very nice topic for an investigator-initiated trial, in Canada and the U.S.”

Head-to-head trials that are well designed will help answer “very important questions” about which treatment strategies have the best outcomes, but doing so requires fortitude, according to Dr. Colombel. “The Dutch have the guts to conduct the LIRIC trial,” he said. In it, patients with Crohn’s disease in the terminal ileum, who have failed steroids or immune therapy, will be assigned randomly to either laparoscopic ileocolic resection or infliximab, the first available biosimilar. Sixty participants have enrolled to date, he said.

These types of studies could also help delineate how best to employ combination therapies. “What I propose for this kind of study is an intensive therapy combining biologics very early in patients with bad prognoses, and looking at the long-term outcome using bowel image,” Dr. Colombel said. These data, and others indicating the most appropriate length of treatment in patients with varying states of disease, are Dr. Colombel’s personal “top choice” for investigation. The excitement that personalized medicine has engendered across the specialities has so far not resulted in specific, validated treatments for IBD patients. However, the question of how to use personal characteristics and serologic and genetic markers to create predictive models for which patients will need either step-up or top-down therapies, accounting for their individual risk of complication, is what he said is among the most “important [question] we need to answer because the choice of early therapy will depend on this predictor,” according to Dr. Colombel.

The question of which treatment targets are best remains unclear but is important to decipher, according to Dr. Colombel, who said simple studies comparing outcomes when patients are treated to symptoms vs. treated to biomarker measurements are needed, as well as the importance of mucosal healing vs. symptom improvement. “This is important because there is discordance between endoscopy and histology,” said Dr. Colombel. “Persistent histologic inflammation is frequently associated with bad outcomes.”

However, endoscopic scoring itself is another area Dr. Colombel said is worth investigating, especially when it comes to validating endpoints such as those in the Crohn’s Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn’s Disease (SES-CD), which will help determine remission cutoffs. Also, endoscopic scoring in comparison with live video and imaging still need standardized approaches. “When you see how it is done in the U.S., it is generally very poor,” Dr. Colombel said.

The biggest obstacles of all when it comes to independent investigation in the United States, according to Frenchman Dr. Colombel, is heavy regulation and cost. “In France, [conducting trials] was considered part of my job. I was not compensated. It is different here.”

Dr. Colombel has numerous financial ties to the pharmaceutical industry, including AB Science, Amgen, Baxter, Bristol-Meyers Squibb, and Merck, among several others.

[email protected]


On Twitter @whitneymcknight

ORLANDO – Independent investigators eager to author studies that have notable impact on the field of inflammatory bowel disease have plenty of important paths to pursue, according to Dr. Jean-Frederic Colombel, a professor of gastroenterology at Mt. Sinai Hospital in New York.

“Over the next 3-5 years, we will have a lot of new drugs, which is nice, but we don’t yet know how to use them, or which ones to use,” Dr. Colombel said during a presentation on the future of the field at this year’s meeting of the annual Advances in Inflammatory Bowel Disease, sponsored by the Crohn’s and Colitis Foundation of America.

Whitney McKnight/Frontline Medical Media

A host of biologics including vedolizumab, recently indicated by the U.S. Food and Drug Administration for ulcerative colitis and Crohn’s disease, and ustekinumab, currently in phase III studies for Crohn’s disease, are set to revolutionize treatment at a time when the field is already undergoing great change, according to Dr. Colombel. The result, he says, is that despite “formidable” challenges in recruitment and funding, “huge opportunities” exist for investigators willing to collaborate and be creative.

Studies that elucidate the natural history of Crohn’s disease and colitis offer insight into the efficacy of various treatment strategies, help determine whether to target symptoms or biomarkers, and answer whether combination therapies are safe and effective in certain patients, among others, are what Dr. Colombel says he hopes will help improve the field as the drug pipeline continues to grow.

He stipulated a caveat, however, “I strongly believe we need some new study designs.” Although he noted that trials needn’t be complicated, they should be long enough to collect sorely needed prospective data. “These can only be done in investigator-initiated trials because of the time frames,” Dr. Colombel urged the audience of young investigators and their colleagues.

A fieldwide shift in thinking about ulcerative colitis and Crohn’s disease as chronic, progressive diseases, rather than intermittent afflictions has already helped generate new study endpoints such as the Lémann Score, an index of progressive bowel damage that allows researchers to better track the history of IBD in patients, and thus provide a window of opportunity for interventions, said Dr. Colombel.

To wit, the CURE study, conducted by the French IBD society GITAID, is a 5-year, prospective study of patients whose early Crohn’s disease is treated with the biologic adalimumab. The Lémann Score is used to screen patients at the end of each successive year, in order to adjust their treatment to reach the final endpoint of deep remission by year 5 when several indicators are measured, including bowel image, level of disability, and whether there was the need for surgery. Dr. Colombel said the novel design of the study, which has already recruited 60 patients, with successive endpoints to evaluate new drugs and strategies over longer periods of time shows it is “feasible” to collect longitudinal data.

The field also has a responsibility to conduct randomly assigned controlled trials to demonstrate the comparative effectiveness, safety, immunogenicity, and cost benefits of the rapidly emerging spate of biosimilars, particularly since there is not global agreement about their use, according to Dr. Colombel. Their approval for IBD in Europe is “highly disputable ... I think this could be a very nice topic for an investigator-initiated trial, in Canada and the U.S.”

Head-to-head trials that are well designed will help answer “very important questions” about which treatment strategies, including the use of biosimilars, have the best outcomes, but doing so requires fortitude, according to Dr. Colombel. “The Dutch have the guts to conduct the LIRIC trial,” he said. In it, patients with Crohn’s disease in the terminal ileum, who have failed steroids or immune therapy, will be assigned randomly to either laparoscopic ileocolic resection or infliximab, the first available biosimilar. Sixty participants have enrolled to date, he said.

These types of studies could also help delineate how best to employ combination therapies. “What I propose for this kind of study is an intensive therapy combining biologics very early in patients with bad prognoses, and looking at the long-term outcome using bowel image,” Dr. Colombel said. These data, and others indicating the most appropriate length of treatment in patients with varying states of disease, are Dr. Colombel’s personal “top choice” for investigation.

The excitement that personalized medicine has engendered across the specialities has so far not resulted in specific, validated treatments for IBD patients. However, the question of how to use personal characteristics, serologic and genetic markers to create predictive models for which patients will need either step-up or top-down therapies, accounting for their individual risk of complication, is what he said is among the most “important [question] we need to answer because the choice of early therapy will depend on this predictor,” according to Dr. Colombel.

The question of which treatment targets are best remains unclear but is important to decipher, according to Dr. Colombel, who said simple studies comparing outcomes when patients are treated to symptoms vs. treated to biomarker measurements are needed. Whether to treat to certain medication trough levels vs. symptom relief is also a pressing need, as well as is the importance of mucosal healing vs. symptoms. “This is important because there is discordance between endoscopy and histology,” said Dr. Colombel. “Persistent histologic inflammation is frequently associated with bad outcomes.”

However, endoscopic scoring itself is another area Dr. Colombel said is worth investigating, especially when it comes to validating endpoints such as those in the Crohn’s Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn’s Disease (SES-CD), which will help determine remission cut offs. Also, using endoscopic scores in comparison with live video and imaging still need standardized approaches. “When you see how it is done in the U.S., it is generally very poor,” Dr. Colombel said.

The biggest obstacles of all when it comes to independent investigation in the United States, according to Frenchman Dr. Colombel, is heavy regulation and cost. “In France, [conducting trials] was considered part of my job. I was not compensated. It is different here.”

Despite that, he said successful studies are a matter of desire. “You have to have dedicated people who want to run these studies and who can meet often and drive the process, and be ready to recruit patients.”

Dr. Colombel has numerous financial ties to the pharmaceutical industry, including AB Science, Amgen, Baxter, Bristol-Meyers Squibb, Merck, Nutrition Science Partners, Teva, and Vertex, among several others.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Independent investigators eager to author studies that have notable impact on the field of inflammatory bowel disease have plenty of important paths to pursue, according to Dr. Jean-Frederic Colombel, a professor of gastroenterology at Mt. Sinai Hospital in New York.

“Over the next 3-5 years, we will have a lot of new drugs, which is nice, but we don’t yet know how to use them, or which ones to use,” Dr. Colombel said during a presentation on the future of the field at this year’s meeting of the annual Advances in Inflammatory Bowel Disease, sponsored by the Crohn’s and Colitis Foundation of America.

Whitney McKnight/Frontline Medical Media

A host of biologics including vedolizumab, recently indicated by the U.S. Food and Drug Administration for ulcerative colitis and Crohn’s disease, and ustekinumab, currently in phase III studies for Crohn’s disease, are set to revolutionize treatment at a time when the field is already undergoing great change, according to Dr. Colombel. The result, he says, is that despite “formidable” challenges in recruitment and funding, “huge opportunities” exist for investigators willing to collaborate and be creative.

Studies that elucidate the natural history of Crohn’s disease and colitis offer insight into the efficacy of various treatment strategies, help determine whether to target symptoms or biomarkers, and answer whether combination therapies are safe and effective in certain patients, among others, are what Dr. Colombel says he hopes will help improve the field as the drug pipeline continues to grow.

He stipulated a caveat, however, “I strongly believe we need some new study designs.” Although he noted that trials needn’t be complicated, they should be long enough to collect sorely needed prospective data. “These can only be done in investigator-initiated trials because of the time frames,” Dr. Colombel urged the audience of young investigators and their colleagues.

A fieldwide shift in thinking about ulcerative colitis and Crohn’s disease as chronic, progressive diseases, rather than intermittent afflictions has already helped generate new study endpoints such as the Lémann Score, an index of progressive bowel damage that allows researchers to better track the history of IBD in patients, and thus provide a window of opportunity for interventions, said Dr. Colombel.

To wit, the CURE study, conducted by the French IBD society GITAID, is a 5-year, prospective study of patients whose early Crohn’s disease is treated with the biologic adalimumab. The Lémann Score is used to screen patients at the end of each successive year, in order to adjust their treatment to reach the final endpoint of deep remission by year 5 when several indicators are measured, including bowel image, level of disability, and whether there was the need for surgery. Dr. Colombel said the novel design of the study, which has already recruited 60 patients, with successive endpoints to evaluate new drugs and strategies over longer periods of time shows it is “feasible” to collect longitudinal data.

The field also has a responsibility to conduct randomly assigned controlled trials to demonstrate the comparative effectiveness, safety, immunogenicity, and cost benefits of the rapidly emerging spate of biosimilars, particularly since there is not global agreement about their use, according to Dr. Colombel. Their approval for IBD in Europe is “highly disputable ... I think this could be a very nice topic for an investigator-initiated trial, in Canada and the U.S.”

Head-to-head trials that are well designed will help answer “very important questions” about which treatment strategies, including the use of biosimilars, have the best outcomes, but doing so requires fortitude, according to Dr. Colombel. “The Dutch have the guts to conduct the LIRIC trial,” he said. In it, patients with Crohn’s disease in the terminal ileum, who have failed steroids or immune therapy, will be assigned randomly to either laparoscopic ileocolic resection or infliximab, the first available biosimilar. Sixty participants have enrolled to date, he said.

These types of studies could also help delineate how best to employ combination therapies. “What I propose for this kind of study is an intensive therapy combining biologics very early in patients with bad prognoses, and looking at the long-term outcome using bowel image,” Dr. Colombel said. These data, and others indicating the most appropriate length of treatment in patients with varying states of disease, are Dr. Colombel’s personal “top choice” for investigation.

The excitement that personalized medicine has engendered across the specialities has so far not resulted in specific, validated treatments for IBD patients. However, the question of how to use personal characteristics, serologic and genetic markers to create predictive models for which patients will need either step-up or top-down therapies, accounting for their individual risk of complication, is what he said is among the most “important [question] we need to answer because the choice of early therapy will depend on this predictor,” according to Dr. Colombel.

The question of which treatment targets are best remains unclear but is important to decipher, according to Dr. Colombel, who said simple studies comparing outcomes when patients are treated to symptoms vs. treated to biomarker measurements are needed. Whether to treat to certain medication trough levels vs. symptom relief is also a pressing need, as well as is the importance of mucosal healing vs. symptoms. “This is important because there is discordance between endoscopy and histology,” said Dr. Colombel. “Persistent histologic inflammation is frequently associated with bad outcomes.”

However, endoscopic scoring itself is another area Dr. Colombel said is worth investigating, especially when it comes to validating endpoints such as those in the Crohn’s Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn’s Disease (SES-CD), which will help determine remission cut offs. Also, using endoscopic scores in comparison with live video and imaging still need standardized approaches. “When you see how it is done in the U.S., it is generally very poor,” Dr. Colombel said.

The biggest obstacles of all when it comes to independent investigation in the United States, according to Frenchman Dr. Colombel, is heavy regulation and cost. “In France, [conducting trials] was considered part of my job. I was not compensated. It is different here.”

Despite that, he said successful studies are a matter of desire. “You have to have dedicated people who want to run these studies and who can meet often and drive the process, and be ready to recruit patients.”

Dr. Colombel has numerous financial ties to the pharmaceutical industry, including AB Science, Amgen, Baxter, Bristol-Meyers Squibb, Merck, Nutrition Science Partners, Teva, and Vertex, among several others.

[email protected]

On Twitter @whitneymcknight

ORLANDO – Independent investigators eager to author studies that have notable impact on the field of inflammatory bowel disease have plenty of important paths to pursue, according to Dr. Jean-Frederic Colombel, a professor of gastroenterology at Mt. Sinai Hospital in New York.

“Over the next 3-5 years, we will have a lot of new drugs, which is nice, but we don’t yet know how to use them, or which ones to use,” Dr. Colombel said during a presentation on the future of the field at this year’s meeting of the annual Advances in Inflammatory Bowel Disease, sponsored by the Crohn’s and Colitis Foundation of America.

Whitney McKnight/Frontline Medical Media

A host of biologics including vedolizumab, recently indicated by the U.S. Food and Drug Administration for ulcerative colitis and Crohn’s disease, and ustekinumab, currently in phase III studies for Crohn’s disease, are set to revolutionize treatment at a time when the field is already undergoing great change, according to Dr. Colombel. The result, he says, is that despite “formidable” challenges in recruitment and funding, “huge opportunities” exist for investigators willing to collaborate and be creative.

Studies that elucidate the natural history of Crohn’s disease and colitis offer insight into the efficacy of various treatment strategies, help determine whether to target symptoms or biomarkers, and answer whether combination therapies are safe and effective in certain patients, among others, are what Dr. Colombel says he hopes will help improve the field as the drug pipeline continues to grow.

He stipulated a caveat, however, “I strongly believe we need some new study designs.” Although he noted that trials needn’t be complicated, they should be long enough to collect sorely needed prospective data. “These can only be done in investigator-initiated trials because of the time frames,” Dr. Colombel urged the audience of young investigators and their colleagues.

A fieldwide shift in thinking about ulcerative colitis and Crohn’s disease as chronic, progressive diseases, rather than intermittent afflictions has already helped generate new study endpoints such as the Lémann Score, an index of progressive bowel damage that allows researchers to better track the history of IBD in patients, and thus provide a window of opportunity for interventions, said Dr. Colombel.

To wit, the CURE study, conducted by the French IBD society GITAID, is a 5-year, prospective study of patients whose early Crohn’s disease is treated with the biologic adalimumab. The Lémann Score is used to screen patients at the end of each successive year, in order to adjust their treatment to reach the final endpoint of deep remission by year 5 when several indicators are measured, including bowel image, level of disability, and whether there was the need for surgery. Dr. Colombel said the novel design of the study, which has already recruited 60 patients, with successive endpoints to evaluate new drugs and strategies over longer periods of time shows it is “feasible” to collect longitudinal data.

The field also has a responsibility to conduct randomly assigned controlled trials to demonstrate the comparative effectiveness, safety, immunogenicity, and cost benefits of the rapidly emerging spate of biosimilars, particularly since there is not global agreement about their use, according to Dr. Colombel. Their approval for IBD in Europe is “highly disputable ... I think this could be a very nice topic for an investigator-initiated trial, in Canada and the U.S.”

Head-to-head trials that are well designed will help answer “very important questions” about which treatment strategies, including the use of biosimilars, have the best outcomes, but doing so requires fortitude, according to Dr. Colombel. “The Dutch have the guts to conduct the LIRIC trial,” he said. In it, patients with Crohn’s disease in the terminal ileum, who have failed steroids or immune therapy, will be assigned randomly to either laparoscopic ileocolic resection or infliximab, the first available biosimilar. Sixty participants have enrolled to date, he said.

These types of studies could also help delineate how best to employ combination therapies. “What I propose for this kind of study is an intensive therapy combining biologics very early in patients with bad prognoses, and looking at the long-term outcome using bowel image,” Dr. Colombel said. These data, and others indicating the most appropriate length of treatment in patients with varying states of disease, are Dr. Colombel’s personal “top choice” for investigation.

The excitement that personalized medicine has engendered across the specialities has so far not resulted in specific, validated treatments for IBD patients. However, the question of how to use personal characteristics, serologic and genetic markers to create predictive models for which patients will need either step-up or top-down therapies, accounting for their individual risk of complication, is what he said is among the most “important [question] we need to answer because the choice of early therapy will depend on this predictor,” according to Dr. Colombel.

The question of which treatment targets are best remains unclear but is important to decipher, according to Dr. Colombel, who said simple studies comparing outcomes when patients are treated to symptoms vs. treated to biomarker measurements are needed. Whether to treat to certain medication trough levels vs. symptom relief is also a pressing need, as well as is the importance of mucosal healing vs. symptoms. “This is important because there is discordance between endoscopy and histology,” said Dr. Colombel. “Persistent histologic inflammation is frequently associated with bad outcomes.”

However, endoscopic scoring itself is another area Dr. Colombel said is worth investigating, especially when it comes to validating endpoints such as those in the Crohn’s Disease Index of Severity (CDEIS), and Simple Endoscopic Score for Crohn’s Disease (SES-CD), which will help determine remission cut offs. Also, using endoscopic scores in comparison with live video and imaging still need standardized approaches. “When you see how it is done in the U.S., it is generally very poor,” Dr. Colombel said.

The biggest obstacles of all when it comes to independent investigation in the United States, according to Frenchman Dr. Colombel, is heavy regulation and cost. “In France, [conducting trials] was considered part of my job. I was not compensated. It is different here.”

Despite that, he said successful studies are a matter of desire. “You have to have dedicated people who want to run these studies and who can meet often and drive the process, and be ready to recruit patients.”

Dr. Colombel has numerous financial ties to the pharmaceutical industry, including AB Science, Amgen, Baxter, Bristol-Meyers Squibb, Merck, Nutrition Science Partners, Teva, and Vertex, among several others.

[email protected]

On Twitter @whitneymcknight