IBD & Intestinal Disorders

The novel coronavirus (2019-nCoV) shows evidence of causing gastrointestinal symptoms and has the potential to be transmitted by the fecal-oral route, according to a new report from physicians at Shanghai Jiao Tong University, published online (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054).

The virus’s respiratory symptoms are well documented and suggest primary transmission by droplet or contact, while other symptoms such as diarrhea, nausea, vomiting, and abdominal discomfort are less common and appear to vary between populations. The SARS coronavirus showed up in stool, even sometimes in patients discharged from the hospital. In a study of hospitalized patients in Wuhan, China, 10.1% of coronavirus patients had diarrhea and nausea in the 1-2 days before onset of fever and dyspnea. The first U.S. patient to be diagnosed had a 2-day history of nausea and vomiting, and had a loose bowel movement on the second day in the hospital. Clinicians later confirmed the presence of viral RNA in both the patient’s stool and airway.

The authors say that researchers in China have isolated viral RNA from the stool of two patients (unpublished), and it has been found in saliva, suggesting the possibility of the salivary gland as an infection or transmission route.

The authors maintain that previous studies likely overlooked or neglected patients who had mild intestinal symptoms. “Many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” the authors wrote.

Like other coronaviruses, it appears that 2019-nCoV infects cells through an interaction between viral transmembrane spike glycoprotein (S-protein) receptor-binding domain, and the cell receptors angiotensin-converting enzyme 2 (ACE-2) and host cellular transmembrane serine protease (TMPRSS). Transcriptome analysis has shown that human lung AT2 cells express ACE-2 and TMPRSS, but esophagus upper and stratified epithelial cells also express both factors, as do stratified epithelial cells and absorptive enterocytes in the ileum and colon.

The researchers call for investigation into ACE-2 fusion proteins and TMPRSS inhibitors for diagnosis, prophylaxis, or treatment of COVID-19.

The authors also noted that COVID-19 has been linked to mild to moderate liver injury as revealed by elevated aminotransferases, hypoproteinemia and prothrombin time prolongation. This also has precedent in that the SARS coronavirus can infect the liver, and biopsies revealed mitoses and apoptosis, along with other abnormalities. SARS-associated hepatitis may be the result of viral hepatitis, immune overreaction, or a secondary effect of antiviral medications or other drugs. Little is known to date about the ability of 2019-nCoV to infect the liver, but single-cell RNA sequencing data from two distinct cohorts showed more ACE-2 expression in cholangiocytes (59.7%) than hepatocytes (2.6%), which indicates that the virus might directly affect intrahepatic bile ducts.

The authors had no sources of funding or financial conflicts.

SOURCE: GU J et al. Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054.

*This story was updated on 4/10.2020.

The novel coronavirus (2019-nCoV) shows evidence of causing gastrointestinal symptoms and has the potential to be transmitted by the fecal-oral route, according to a new report from physicians at Shanghai Jiao Tong University, published online (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054).

The virus’s respiratory symptoms are well documented and suggest primary transmission by droplet or contact, while other symptoms such as diarrhea, nausea, vomiting, and abdominal discomfort are less common and appear to vary between populations. The SARS coronavirus showed up in stool, even sometimes in patients discharged from the hospital. In a study of hospitalized patients in Wuhan, China, 10.1% of coronavirus patients had diarrhea and nausea in the 1-2 days before onset of fever and dyspnea. The first U.S. patient to be diagnosed had a 2-day history of nausea and vomiting, and had a loose bowel movement on the second day in the hospital. Clinicians later confirmed the presence of viral RNA in both the patient’s stool and airway.

The authors say that researchers in China have isolated viral RNA from the stool of two patients (unpublished), and it has been found in saliva, suggesting the possibility of the salivary gland as an infection or transmission route.

The authors maintain that previous studies likely overlooked or neglected patients who had mild intestinal symptoms. “Many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” the authors wrote.

Like other coronaviruses, it appears that 2019-nCoV infects cells through an interaction between viral transmembrane spike glycoprotein (S-protein) receptor-binding domain, and the cell receptors angiotensin-converting enzyme 2 (ACE-2) and host cellular transmembrane serine protease (TMPRSS). Transcriptome analysis has shown that human lung AT2 cells express ACE-2 and TMPRSS, but esophagus upper and stratified epithelial cells also express both factors, as do stratified epithelial cells and absorptive enterocytes in the ileum and colon.

The researchers call for investigation into ACE-2 fusion proteins and TMPRSS inhibitors for diagnosis, prophylaxis, or treatment of COVID-19.

The authors also noted that COVID-19 has been linked to mild to moderate liver injury as revealed by elevated aminotransferases, hypoproteinemia and prothrombin time prolongation. This also has precedent in that the SARS coronavirus can infect the liver, and biopsies revealed mitoses and apoptosis, along with other abnormalities. SARS-associated hepatitis may be the result of viral hepatitis, immune overreaction, or a secondary effect of antiviral medications or other drugs. Little is known to date about the ability of 2019-nCoV to infect the liver, but single-cell RNA sequencing data from two distinct cohorts showed more ACE-2 expression in cholangiocytes (59.7%) than hepatocytes (2.6%), which indicates that the virus might directly affect intrahepatic bile ducts.

The authors had no sources of funding or financial conflicts.

SOURCE: GU J et al. Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054.

*This story was updated on 4/10.2020.

The novel coronavirus (2019-nCoV) shows evidence of causing gastrointestinal symptoms and has the potential to be transmitted by the fecal-oral route, according to a new report from physicians at Shanghai Jiao Tong University, published online (Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054).

The virus’s respiratory symptoms are well documented and suggest primary transmission by droplet or contact, while other symptoms such as diarrhea, nausea, vomiting, and abdominal discomfort are less common and appear to vary between populations. The SARS coronavirus showed up in stool, even sometimes in patients discharged from the hospital. In a study of hospitalized patients in Wuhan, China, 10.1% of coronavirus patients had diarrhea and nausea in the 1-2 days before onset of fever and dyspnea. The first U.S. patient to be diagnosed had a 2-day history of nausea and vomiting, and had a loose bowel movement on the second day in the hospital. Clinicians later confirmed the presence of viral RNA in both the patient’s stool and airway.

The authors say that researchers in China have isolated viral RNA from the stool of two patients (unpublished), and it has been found in saliva, suggesting the possibility of the salivary gland as an infection or transmission route.

The authors maintain that previous studies likely overlooked or neglected patients who had mild intestinal symptoms. “Many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” the authors wrote.

Like other coronaviruses, it appears that 2019-nCoV infects cells through an interaction between viral transmembrane spike glycoprotein (S-protein) receptor-binding domain, and the cell receptors angiotensin-converting enzyme 2 (ACE-2) and host cellular transmembrane serine protease (TMPRSS). Transcriptome analysis has shown that human lung AT2 cells express ACE-2 and TMPRSS, but esophagus upper and stratified epithelial cells also express both factors, as do stratified epithelial cells and absorptive enterocytes in the ileum and colon.

The researchers call for investigation into ACE-2 fusion proteins and TMPRSS inhibitors for diagnosis, prophylaxis, or treatment of COVID-19.

The authors also noted that COVID-19 has been linked to mild to moderate liver injury as revealed by elevated aminotransferases, hypoproteinemia and prothrombin time prolongation. This also has precedent in that the SARS coronavirus can infect the liver, and biopsies revealed mitoses and apoptosis, along with other abnormalities. SARS-associated hepatitis may be the result of viral hepatitis, immune overreaction, or a secondary effect of antiviral medications or other drugs. Little is known to date about the ability of 2019-nCoV to infect the liver, but single-cell RNA sequencing data from two distinct cohorts showed more ACE-2 expression in cholangiocytes (59.7%) than hepatocytes (2.6%), which indicates that the virus might directly affect intrahepatic bile ducts.

The authors had no sources of funding or financial conflicts.

SOURCE: GU J et al. Gastroenterology. 2020 March 3. doi: 10.1053/j.gastro.2020.02.054.

*This story was updated on 4/10.2020.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

MAUI, HAWAII – The problem with doing a breath test for small intestinal bacterial overgrowth before starting rifaximin (Xifaxan) for diarrhea-predominant irritable bowel syndrome is that you can’t trust the results, according to IBS expert Lin Chang, MD, a professor and vice chief of the division of digestive diseases at the University of California, Los Angeles.

Rifaximin is an antibiotic that works in the intestines but is not absorbed by the body, and is approved for irritable bowel syndrome with diarrhea (IBS-D). It’s a second-line option for moderate illness when diet, OTC medications, and other easier options don’t do the trick. Endpoints were met by about 10% more patients on rifaximin than placebo in randomized trials, perhaps by resetting gut microbiota.

“It was a small therapeutic gain, but it was statistically significant,” Dr. Chang said at the Gastroenterology Updates, IBD, Liver Disease Conference. In her own practice, she said it sometimes helps even with bloating and abdominal distension, two of the most vexing problems in IBS-D.

However, symptoms come back after 3-6 months, and prices approach $2,000 for the 2-week IBS-D course. Insurance doesn’t always fully cover it, and the Food and Drug Administration has capped treatments at three.

That’s left providers wondering what to do when people ask for rifaximin after seeing it advertised and eager for some way to predict if it will work or not. Some clinicians have turned to a breath test for small-intestinal bacterial overgrowth (SIBO) before prescribing rifaximin because there is evidence that SIBO contributes to IBS-D, but others have not. It’s a contentious issue in IBS medicine, Dr. Chang said.

A recent open-label study funded by rifaximin maker Salix Pharmaceuticals made a case for testing. Among 93 IBS-D patients, 60% with a positive breath test at baseline had reduced pain, diarrhea, and other symptoms after 550 mg three times daily for 2 weeks, versus 26% with a negative test (Am J Gastroenterol. 2019 Dec;114[12]:1886-93).

Even so, when asked after her IBS presentation, Dr. Chang said she doesn’t breath test because it doesn’t make sense. Even with positive results, “you don’t really know if they have SIBO or not. Sometimes healthy controls have a positive test, and some people with IBS who end up responding to rifaximin have a negative breath test. It’s up to you, [but] it doesn’t correlate” with outcomes, she said.

Indeed, a letter in response to the study made a strong case that nine of the subjects should have been counted as having a negative, not positive, breath test, and if they had, the difference in outcome would have disappeared (Am J Gastroenterol. 2020 Mar 2. doi: 10.14309/ajg.0000000000000569).

Dr. Chang has opted for an empiric approach. “I just treat patients who meet the criteria used in the clinical trials,” such as moderate abdominal pain and bloating, she said (for example, N Engl J Med. 2011 Jan 6;364[1]:22-32).

And she doesn’t push if people can’t afford rifaximin. Some turn to other antibiotics, like metronidazole (Flagyl) or ciprofloxacin (Cipro), which are absorbed in the GI tract, but Dr. Chang said symptoms will recur after a few months regardless of the antibiotic. “You don’t want all these young women to be given antibiotics over and over again. Their symptoms are just going to come back, and you are going to have to learn how to treat them anyway,” she said.

Instead, she moves on to other options when patients are at the point where they need prescription pharmaceuticals. One of her top choices is the tricyclic antidepressant amitriptyline. It helps with the pain; the anticholinergic effects counter the diarrhea; and the sedative effects help patients who have a hard time sleeping. Sleep problems make IBS-D symptoms worse, Dr. Chang said.

[email protected]

MAUI, HAWAII – The problem with doing a breath test for small intestinal bacterial overgrowth before starting rifaximin (Xifaxan) for diarrhea-predominant irritable bowel syndrome is that you can’t trust the results, according to IBS expert Lin Chang, MD, a professor and vice chief of the division of digestive diseases at the University of California, Los Angeles.

Rifaximin is an antibiotic that works in the intestines but is not absorbed by the body, and is approved for irritable bowel syndrome with diarrhea (IBS-D). It’s a second-line option for moderate illness when diet, OTC medications, and other easier options don’t do the trick. Endpoints were met by about 10% more patients on rifaximin than placebo in randomized trials, perhaps by resetting gut microbiota.

“It was a small therapeutic gain, but it was statistically significant,” Dr. Chang said at the Gastroenterology Updates, IBD, Liver Disease Conference. In her own practice, she said it sometimes helps even with bloating and abdominal distension, two of the most vexing problems in IBS-D.

However, symptoms come back after 3-6 months, and prices approach $2,000 for the 2-week IBS-D course. Insurance doesn’t always fully cover it, and the Food and Drug Administration has capped treatments at three.

That’s left providers wondering what to do when people ask for rifaximin after seeing it advertised and eager for some way to predict if it will work or not. Some clinicians have turned to a breath test for small-intestinal bacterial overgrowth (SIBO) before prescribing rifaximin because there is evidence that SIBO contributes to IBS-D, but others have not. It’s a contentious issue in IBS medicine, Dr. Chang said.

A recent open-label study funded by rifaximin maker Salix Pharmaceuticals made a case for testing. Among 93 IBS-D patients, 60% with a positive breath test at baseline had reduced pain, diarrhea, and other symptoms after 550 mg three times daily for 2 weeks, versus 26% with a negative test (Am J Gastroenterol. 2019 Dec;114[12]:1886-93).

Even so, when asked after her IBS presentation, Dr. Chang said she doesn’t breath test because it doesn’t make sense. Even with positive results, “you don’t really know if they have SIBO or not. Sometimes healthy controls have a positive test, and some people with IBS who end up responding to rifaximin have a negative breath test. It’s up to you, [but] it doesn’t correlate” with outcomes, she said.

Indeed, a letter in response to the study made a strong case that nine of the subjects should have been counted as having a negative, not positive, breath test, and if they had, the difference in outcome would have disappeared (Am J Gastroenterol. 2020 Mar 2. doi: 10.14309/ajg.0000000000000569).

Dr. Chang has opted for an empiric approach. “I just treat patients who meet the criteria used in the clinical trials,” such as moderate abdominal pain and bloating, she said (for example, N Engl J Med. 2011 Jan 6;364[1]:22-32).

And she doesn’t push if people can’t afford rifaximin. Some turn to other antibiotics, like metronidazole (Flagyl) or ciprofloxacin (Cipro), which are absorbed in the GI tract, but Dr. Chang said symptoms will recur after a few months regardless of the antibiotic. “You don’t want all these young women to be given antibiotics over and over again. Their symptoms are just going to come back, and you are going to have to learn how to treat them anyway,” she said.

Instead, she moves on to other options when patients are at the point where they need prescription pharmaceuticals. One of her top choices is the tricyclic antidepressant amitriptyline. It helps with the pain; the anticholinergic effects counter the diarrhea; and the sedative effects help patients who have a hard time sleeping. Sleep problems make IBS-D symptoms worse, Dr. Chang said.

[email protected]

MAUI, HAWAII – The problem with doing a breath test for small intestinal bacterial overgrowth before starting rifaximin (Xifaxan) for diarrhea-predominant irritable bowel syndrome is that you can’t trust the results, according to IBS expert Lin Chang, MD, a professor and vice chief of the division of digestive diseases at the University of California, Los Angeles.

Rifaximin is an antibiotic that works in the intestines but is not absorbed by the body, and is approved for irritable bowel syndrome with diarrhea (IBS-D). It’s a second-line option for moderate illness when diet, OTC medications, and other easier options don’t do the trick. Endpoints were met by about 10% more patients on rifaximin than placebo in randomized trials, perhaps by resetting gut microbiota.

“It was a small therapeutic gain, but it was statistically significant,” Dr. Chang said at the Gastroenterology Updates, IBD, Liver Disease Conference. In her own practice, she said it sometimes helps even with bloating and abdominal distension, two of the most vexing problems in IBS-D.

However, symptoms come back after 3-6 months, and prices approach $2,000 for the 2-week IBS-D course. Insurance doesn’t always fully cover it, and the Food and Drug Administration has capped treatments at three.

That’s left providers wondering what to do when people ask for rifaximin after seeing it advertised and eager for some way to predict if it will work or not. Some clinicians have turned to a breath test for small-intestinal bacterial overgrowth (SIBO) before prescribing rifaximin because there is evidence that SIBO contributes to IBS-D, but others have not. It’s a contentious issue in IBS medicine, Dr. Chang said.

A recent open-label study funded by rifaximin maker Salix Pharmaceuticals made a case for testing. Among 93 IBS-D patients, 60% with a positive breath test at baseline had reduced pain, diarrhea, and other symptoms after 550 mg three times daily for 2 weeks, versus 26% with a negative test (Am J Gastroenterol. 2019 Dec;114[12]:1886-93).

Even so, when asked after her IBS presentation, Dr. Chang said she doesn’t breath test because it doesn’t make sense. Even with positive results, “you don’t really know if they have SIBO or not. Sometimes healthy controls have a positive test, and some people with IBS who end up responding to rifaximin have a negative breath test. It’s up to you, [but] it doesn’t correlate” with outcomes, she said.

Indeed, a letter in response to the study made a strong case that nine of the subjects should have been counted as having a negative, not positive, breath test, and if they had, the difference in outcome would have disappeared (Am J Gastroenterol. 2020 Mar 2. doi: 10.14309/ajg.0000000000000569).

Dr. Chang has opted for an empiric approach. “I just treat patients who meet the criteria used in the clinical trials,” such as moderate abdominal pain and bloating, she said (for example, N Engl J Med. 2011 Jan 6;364[1]:22-32).

And she doesn’t push if people can’t afford rifaximin. Some turn to other antibiotics, like metronidazole (Flagyl) or ciprofloxacin (Cipro), which are absorbed in the GI tract, but Dr. Chang said symptoms will recur after a few months regardless of the antibiotic. “You don’t want all these young women to be given antibiotics over and over again. Their symptoms are just going to come back, and you are going to have to learn how to treat them anyway,” she said.

Instead, she moves on to other options when patients are at the point where they need prescription pharmaceuticals. One of her top choices is the tricyclic antidepressant amitriptyline. It helps with the pain; the anticholinergic effects counter the diarrhea; and the sedative effects help patients who have a hard time sleeping. Sleep problems make IBS-D symptoms worse, Dr. Chang said.

[email protected]

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

[email protected]

SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

[email protected]

SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.

MAUI, HAWAII – There’s a new kid on the block to worry about when it comes to thiopurine pharmacogenetics: Genetic variants in the thiopurine-metabolizing enzyme nudix hydrolase 15 have been linked to a markedly increased risk of thiopurine myelosuppression among inflammatory bowel disease patients.

The Food and Drug Administration and others already recommend screening for genetic variants in thiopurine methyltransferase (TPMT), another enzyme that metabolizes thiopurine. Polymorphisms lead to TMPT dysfunction, accumulation of cytotoxic metabolites, and increased risk of thiopurine-induced myelosuppression (TIM). Carriers are advised to use reduced doses with careful drug monitoring, or to skip thiopurines altogether.

A similar picture is emerging for nudix hydrolase 15 (NUDT15). It’s been known for several years that genetic variants are not uncommon among East Asian people and lead to TIM, but their prevalence and impact among people of European decent wasn’t clearly understood until now.

Investigators led by Gareth Walker, MBBS, of the Royal Devon and Exeter Hospital in Exeter, England, compared rates of problematic TMPT and NUDT15 variants among European inflammatory bowel disease patients who had developed TIM and those who had not, about 1,000 patients in all. The majority were on azathioprine and had Crohn’s disease. Finnish people were excluded because “their unique genetic background ... has led to the enrichment of some disease-causing gene variants and losses of others,” according to the study, which was published in JAMA.

Carriage of any of three coding NUDT15 variants greatly increased the risk of TIM (odds ratio, 27.3; 95% confidence interval, 9.3-116.7), independent of TPMT genotype and thiopurine dose. A particular variant – an in-frame deletion in NUDT15 – increased the risk 38-fold (95% CI, 5.1-286.1), and was carried by 5.8% of TIM patients.

The analysis also confirmed the importance of TPMT variants, which were found in 30.5% of TIM patients (95/311) versus 16.4% (100/608) of patients who did not develop TIM.

“Patients with variants of either NUDT15 or TPMT, or among those with variants of both genes, had a faster onset of TIM, more severe TIM, and had a greater need for granulocyte colony–stimulating factor rescue therapy. ... Our data suggest that pretreatment sequencing of the NUDT15 gene ... may be considered prior to initiation of thiopurine therapy,” the team concluded.

The prevalence of problematic NUDT15 variants among non-Finnish Europeans is about 1.6%, 6.9% among people from Finland, and almost 30% among East Asians. The team estimated NUDT15 would have to be genotyped in 95 non-Finnish Europeans to prevent one case of TIM; the number is 123 for TPMT. “Given the widespread use of thiopurines” – primarily in rheumatology and transplant medicine, in addition to gastroenterology – “these findings may have ramifications beyond the management of IBD,” the investigators wrote.

M. Alexander Otto/MDedge News

“I do think it’s worthwhile” to screen for NUDT15, said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., who reviewed the study at the Gastroenterology Updates, IBD, Liver Disease Conference. “If you are a homozygote for this, your chance of getting profound leukopenia is very high, so I would probably not use a thiopurine.”

“If you are going to start low dose on everyone” with careful blood monitoring, “I suppose you could just do that, but I would say if you can get” the test and “are reassured the patient is not” carrying problematic NUDT15 or TMPT variants, “then I think you just go ahead and do full dose,” he said.

Testing for the relevant variants is available through the Mayo Clinic and several commercial labs.

“Even though the thiopurine dose is adjusted based on genotype, patients still need to be monitored closely for the development of thiopurine-induced myelosuppression as” TMPT and NUDT15 variants “do not explain all cases of” TIM, Marieke Coenen, PhD, an associate professor of pharmacogenetics at Radboud University Medical Center in Nijmegen, the Netherlands, cautioned in an editorial (Transl Gastroenterol Hepatol. 2019 Dec 12;4:81).

The prevalence of problematic NUDT15 variants is 0.7% among African and 20.7% among Hispanic people.

The work was funded by the National Institutes of Health, Crohn’s & Colitis UK, the Wellcome Trust, and others. Dr. Walker and other investigators reported numerous industry ties. Dr. Loftus is a consultant and/or has research funding from Abbott, Pfizer, and other companies. Dr. Coenen had no disclosures.
 

[email protected]

SOURCE: Walker GJ et al. JAMA. 2019 Feb 26;321(8):773-85.

MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.

“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.

The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.

“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.

M. Alexander Otto/MDedge News

“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”

The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.

Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.

The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.

A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).

The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).

The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.

The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.

The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”

In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”

The mechanism for the association is unknown, the authors said.

The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
 

[email protected]

SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.

MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.

“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.

The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.

“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.

M. Alexander Otto/MDedge News

“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”

The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.

Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.

The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.

A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).

The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).

The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.

The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.

The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”

In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”

The mechanism for the association is unknown, the authors said.

The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
 

[email protected]

SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.

MAUI, HAWAII – A variant in the human leukocyte antigen gene – DQA1*05 – almost doubled the risk of antibodies forming against tumor necrosis factor (TNF) inhibitors in Crohn’s disease patients, irrespective of concomitant immunomodulator use, according to a report in Gastroenterology.

“Pretreatment genetic testing for HLA-DQA1*05 may help personalize the choice of anti-TNF and the need for combination therapy,” concluded investigators led by Aleksejs Sazonovs, of the Wellcome Sanger Institute in Hinxton, England.

The same variant increases the risk of celiac disease, and it is included in commercial celiac genotyping assays. The allele is carried by about 40% of Europeans.

“This is turning into a hot topic; people are talking about it, [and it’s] blowing up on Twitter,” said Edward Loftus, MD, a professor and consultant in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn. “It turns out this is really a significant predictor of immunogenicity. Whatever your risk of developing antibodies, it’s going to double if you have this HLA marker, and it’s common.

M. Alexander Otto/MDedge News

“I think we are going to start [stratifying] our decision on combination [or] monotherapy based on this,” added Dr. Loftus, speaking at the Gastroenterology Updates, IBD, Liver Disease Conference. “I would argue that, if your patient has this marker, it would be criminal to give that patient infliximab monotherapy.”

The finding also begs the question of whether to bypass anti-TNFs altogether if a patient has the marker, Dr. Loftus noted, and just use ustekinumab, vedolizumab, or another agent.

Checking for celiac disease in inflammatory bowel disease isn’t unusual and involves the same gene variant, he added, so payer coverage shouldn’t be much of a problem.

The investigators ran a genome-wide association study on 1,418 biologic-naive Crohn’s patients starting infliximab or adalimumab therapy. Patients were in their 30s, on average, with a disease duration of about 3 years; there were about equal numbers of men and women.

A total of 44% of patients developed antidrug antibodies within a year. Overall, the rate of immunogenicity – defined as an antidrug antibody titer of at least 10 AU/mL – was nearly doubled in HLA-DQA1*05 carriers (hazard ratio, 1.90; 95% confidence interval, 1.60-2.25).

The association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33) and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator, usually azathioprine (HR, 2.01; 95% CI, 1.57-2.58).

The highest rates of immunogenicity, 92% at 1 year, were in HLA-DQA1*05 carriers on infliximab monotherapy. The lowest rates, 10% at 1 year, were in adalimumab patients on combination therapy who didn’t carry the variant. HLA-DQA1*05 was also associated with lower drug persistence rates.

The specific alleles HLA-DQA1*05:01 and HLA-DQA1*05:05 mediated most of the risk.

The study authors advised that “all patients treated with an anti-TNF should be prescribed an immunomodulator to lower the risk of immunogenicity.” Among HLA-DQA1*05 carriers “in whom immunomodulators are contraindicated or not tolerated, clinicians might advise against the use of anti-TNF drugs, particularly infliximab.”

In contrast, “patients who do not carry HLA-DQA1*05 might be given the choice between adalimumab or infliximab combination therapy,” the investigators said. “Patients without the risk allele and a history of adverse drug reactions to thiopurines and/or methotrexate, or who are at high risk of opportunistic infections, might be spared the additional risks of combination therapy and treated with adalimumab monotherapy.”

The mechanism for the association is unknown, the authors said.

The work was funded by the British Society of Gastroenterology, AbbVie, Merck, Pfizer, and others. The authors disclosed numerous ties to those or other pharmaceutical companies. Two authors were employees of AbbVie, marketer of the branded adalimumab Humira.
 

[email protected]

SOURCE: Sazonovs A et al. Gastroenterology. 2020 Jan;158(1):189-99.

Researchers have found three potential gut mechanisms linked to secondary bile acid (SBA) deficiencies implicated in intestinal inflammation in ulcerative colitis (UC), and reported that supplementation may aid in restoring bile acid levels and potentially treating intestinal inflammation, according to a study published in Cell Host & Microbe.

The study identified lower levels of the following gut components in SBA deficiency in colectomy patients with UC, compared with those with familial adenomatous polyposis (FAP): deoxycholic and lithocholic acids (DCA and LCA), the most abundant gut secondary bile acids (SBAs); expression of the genes needed to convert primary bile acids (PBAs) into SBAs; and the number of Ruminococcaceae, one of the few taxa that include bacteria that generate SBAs.

“Our findings confirm that significant changes in bacterial diversity and composition occur in UC versus FAP pouches,” wrote Sidhartha R. Sinha, MD, of Stanford (Calif.) University, and coauthors. “Notably, our finding of decreased Ruminococcaceae in UC, compared to FAP pouch stool, requires further exploration.” They added that this is the first study to identify Ruminococcaceae as a key contributor to the production of LCA or DCA from PBAs.

The study found average DCA counts of 60,957 in FAP versus 1,593 in UC (P = .002), and average LCA counts of 30,644 and 282.9, respectively (P = .001). The study profiled stools from ileal pouches in colectomy patients who had UC (17) or FAP (7), a noninflammatory disease. “Remarkably, our data identify LCA and DCA to be almost undetectable in UC pouch patients,” Dr. Sinha and coauthors wrote. “This striking finding in patients who underwent colectomy suggests that SBAs may play a role in dysregulated metabolism-induced intestinal inflammation.”

The study found that UC pouches demonstrated less bacterial diversity, or alpha-diversity, than FAP pouches, which is in line with previously reported findings (J Inflamm Res. 2017;10:63-73), and had significantly lower expression of bile-acid inducible genes that encode enzymes that transform PBA to SBA.

The researchers also demonstrated that LCA and DCA supplementation reduced intestinal inflammation in mice with UC.

“Our results show that LCA and DCA treatments caused a remarkable and significant decrease in multiple chemokines and cytokines associated with inflammation, including those often increased in intestinal inflammation,” Dr. Sinha and coauthors wrote. However, they found that LCA had no protective effect on dextran sodium sulfate–induced colitis in mice with TGR5-deficient immune cells. The TGR5 bile acid receptor influences the anti-inflammatory effect in SBA supplementation, the study reported.

The researchers have initiated a clinical study (NCT03724175) to investigate the role of SBAs in patients with pouchitis that doesn’t respond to antibiotic therapy. “Insights from this study will further inform our understanding of the role of SBAs in intestinal inflammation and hold promise to provide an effective treatment,” Dr. Sinha and coauthors wrote.

Christian Jobin, PhD, of the University of Florida, Gainesville, said in an interview these findings are consistent with a recent paper that found a correlation between production of SBAs such as DCA and disease remission (ISME J. 2020;14:702-13). Dr. Jobin coauthored a 2018 study that similarly found SBAs have a role in intestinal inflammation (Gastroenterology. 2018;154:1751-63).

“For a long time, secondary bile acid, especially DCA was linked to cell injury, toxicity and even cancer,” he said. “It’s time to rehabilitate this important signaling molecule and recognize its important role in regulating host homeostasis.” The 2018 paper he coauthored showed that injection of DCA into germ-free mice did not promote intestinal pathology. “Actually, DCA was critical in preventing Campylobacter jejune–induced colitis,” he added.

Dr. Sinha received funding from the Crohn’s & Colitis Foundation, Stanford Clinical and Translational Science Award, and Kenneth Rainin Foundation Synergy Award. Coauthors received funding from the National Institutes of Health, the Ann and Bill Swindells Charitable Trust, Leslie and Douglas Ballinger, and the Kenneth Rainin Foundation.

SOURCE: Sinha SR et al. Cell Host Microbe. 2020 Feb 25. doi: 10.1016/j.chom.2020.01.021.

Researchers have found three potential gut mechanisms linked to secondary bile acid (SBA) deficiencies implicated in intestinal inflammation in ulcerative colitis (UC), and reported that supplementation may aid in restoring bile acid levels and potentially treating intestinal inflammation, according to a study published in Cell Host & Microbe.

The study identified lower levels of the following gut components in SBA deficiency in colectomy patients with UC, compared with those with familial adenomatous polyposis (FAP): deoxycholic and lithocholic acids (DCA and LCA), the most abundant gut secondary bile acids (SBAs); expression of the genes needed to convert primary bile acids (PBAs) into SBAs; and the number of Ruminococcaceae, one of the few taxa that include bacteria that generate SBAs.

“Our findings confirm that significant changes in bacterial diversity and composition occur in UC versus FAP pouches,” wrote Sidhartha R. Sinha, MD, of Stanford (Calif.) University, and coauthors. “Notably, our finding of decreased Ruminococcaceae in UC, compared to FAP pouch stool, requires further exploration.” They added that this is the first study to identify Ruminococcaceae as a key contributor to the production of LCA or DCA from PBAs.

The study found average DCA counts of 60,957 in FAP versus 1,593 in UC (P = .002), and average LCA counts of 30,644 and 282.9, respectively (P = .001). The study profiled stools from ileal pouches in colectomy patients who had UC (17) or FAP (7), a noninflammatory disease. “Remarkably, our data identify LCA and DCA to be almost undetectable in UC pouch patients,” Dr. Sinha and coauthors wrote. “This striking finding in patients who underwent colectomy suggests that SBAs may play a role in dysregulated metabolism-induced intestinal inflammation.”

The study found that UC pouches demonstrated less bacterial diversity, or alpha-diversity, than FAP pouches, which is in line with previously reported findings (J Inflamm Res. 2017;10:63-73), and had significantly lower expression of bile-acid inducible genes that encode enzymes that transform PBA to SBA.

The researchers also demonstrated that LCA and DCA supplementation reduced intestinal inflammation in mice with UC.

“Our results show that LCA and DCA treatments caused a remarkable and significant decrease in multiple chemokines and cytokines associated with inflammation, including those often increased in intestinal inflammation,” Dr. Sinha and coauthors wrote. However, they found that LCA had no protective effect on dextran sodium sulfate–induced colitis in mice with TGR5-deficient immune cells. The TGR5 bile acid receptor influences the anti-inflammatory effect in SBA supplementation, the study reported.

The researchers have initiated a clinical study (NCT03724175) to investigate the role of SBAs in patients with pouchitis that doesn’t respond to antibiotic therapy. “Insights from this study will further inform our understanding of the role of SBAs in intestinal inflammation and hold promise to provide an effective treatment,” Dr. Sinha and coauthors wrote.

Christian Jobin, PhD, of the University of Florida, Gainesville, said in an interview these findings are consistent with a recent paper that found a correlation between production of SBAs such as DCA and disease remission (ISME J. 2020;14:702-13). Dr. Jobin coauthored a 2018 study that similarly found SBAs have a role in intestinal inflammation (Gastroenterology. 2018;154:1751-63).

“For a long time, secondary bile acid, especially DCA was linked to cell injury, toxicity and even cancer,” he said. “It’s time to rehabilitate this important signaling molecule and recognize its important role in regulating host homeostasis.” The 2018 paper he coauthored showed that injection of DCA into germ-free mice did not promote intestinal pathology. “Actually, DCA was critical in preventing Campylobacter jejune–induced colitis,” he added.

Dr. Sinha received funding from the Crohn’s & Colitis Foundation, Stanford Clinical and Translational Science Award, and Kenneth Rainin Foundation Synergy Award. Coauthors received funding from the National Institutes of Health, the Ann and Bill Swindells Charitable Trust, Leslie and Douglas Ballinger, and the Kenneth Rainin Foundation.

SOURCE: Sinha SR et al. Cell Host Microbe. 2020 Feb 25. doi: 10.1016/j.chom.2020.01.021.

Researchers have found three potential gut mechanisms linked to secondary bile acid (SBA) deficiencies implicated in intestinal inflammation in ulcerative colitis (UC), and reported that supplementation may aid in restoring bile acid levels and potentially treating intestinal inflammation, according to a study published in Cell Host & Microbe.

The study identified lower levels of the following gut components in SBA deficiency in colectomy patients with UC, compared with those with familial adenomatous polyposis (FAP): deoxycholic and lithocholic acids (DCA and LCA), the most abundant gut secondary bile acids (SBAs); expression of the genes needed to convert primary bile acids (PBAs) into SBAs; and the number of Ruminococcaceae, one of the few taxa that include bacteria that generate SBAs.

“Our findings confirm that significant changes in bacterial diversity and composition occur in UC versus FAP pouches,” wrote Sidhartha R. Sinha, MD, of Stanford (Calif.) University, and coauthors. “Notably, our finding of decreased Ruminococcaceae in UC, compared to FAP pouch stool, requires further exploration.” They added that this is the first study to identify Ruminococcaceae as a key contributor to the production of LCA or DCA from PBAs.

The study found average DCA counts of 60,957 in FAP versus 1,593 in UC (P = .002), and average LCA counts of 30,644 and 282.9, respectively (P = .001). The study profiled stools from ileal pouches in colectomy patients who had UC (17) or FAP (7), a noninflammatory disease. “Remarkably, our data identify LCA and DCA to be almost undetectable in UC pouch patients,” Dr. Sinha and coauthors wrote. “This striking finding in patients who underwent colectomy suggests that SBAs may play a role in dysregulated metabolism-induced intestinal inflammation.”

The study found that UC pouches demonstrated less bacterial diversity, or alpha-diversity, than FAP pouches, which is in line with previously reported findings (J Inflamm Res. 2017;10:63-73), and had significantly lower expression of bile-acid inducible genes that encode enzymes that transform PBA to SBA.

The researchers also demonstrated that LCA and DCA supplementation reduced intestinal inflammation in mice with UC.

“Our results show that LCA and DCA treatments caused a remarkable and significant decrease in multiple chemokines and cytokines associated with inflammation, including those often increased in intestinal inflammation,” Dr. Sinha and coauthors wrote. However, they found that LCA had no protective effect on dextran sodium sulfate–induced colitis in mice with TGR5-deficient immune cells. The TGR5 bile acid receptor influences the anti-inflammatory effect in SBA supplementation, the study reported.

The researchers have initiated a clinical study (NCT03724175) to investigate the role of SBAs in patients with pouchitis that doesn’t respond to antibiotic therapy. “Insights from this study will further inform our understanding of the role of SBAs in intestinal inflammation and hold promise to provide an effective treatment,” Dr. Sinha and coauthors wrote.

Christian Jobin, PhD, of the University of Florida, Gainesville, said in an interview these findings are consistent with a recent paper that found a correlation between production of SBAs such as DCA and disease remission (ISME J. 2020;14:702-13). Dr. Jobin coauthored a 2018 study that similarly found SBAs have a role in intestinal inflammation (Gastroenterology. 2018;154:1751-63).

“For a long time, secondary bile acid, especially DCA was linked to cell injury, toxicity and even cancer,” he said. “It’s time to rehabilitate this important signaling molecule and recognize its important role in regulating host homeostasis.” The 2018 paper he coauthored showed that injection of DCA into germ-free mice did not promote intestinal pathology. “Actually, DCA was critical in preventing Campylobacter jejune–induced colitis,” he added.

Dr. Sinha received funding from the Crohn’s & Colitis Foundation, Stanford Clinical and Translational Science Award, and Kenneth Rainin Foundation Synergy Award. Coauthors received funding from the National Institutes of Health, the Ann and Bill Swindells Charitable Trust, Leslie and Douglas Ballinger, and the Kenneth Rainin Foundation.

SOURCE: Sinha SR et al. Cell Host Microbe. 2020 Feb 25. doi: 10.1016/j.chom.2020.01.021.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

For patients with inflammatory bowel disease, 16S ribosomal gene sequencing of lamina propria phagocytes identified microbiota closely associated with inflamed intestinal tissue, according to the results of a pilot study.

This microbiome differed from that of the intestinal mucosa, containing a markedly higher concentration of Proteobacteria, reported Rishu Dheer, PhD, of the University of Miami, and associates. The microbiota also differed between Crohn’s disease and ulcerative colitis, while inflammatory gene expression did not. “The approach used in this study can narrow the spectrum of potentially dysbiotic bacterial populations” in patients with inflammatory bowel disease, the researchers wrote in Cellular and Molecular Gastroenterology and Hepatology.

Recent studies have confirmed intestinal dysbiosis in patients with inflammatory bowel disease, but little is known about disease susceptibility or severity or how microbiota correlate with inflammatory gene expression, the researchers said. They obtained ileal and colonic punch biopsy specimens from 32 patients with inflammatory bowel disease (20 with Crohn’s disease and 12 with ulcerative colitis) and performed 16S ribosomal RNA sequencing of CD11+ phagocytic cells from the lamina propria. They also performed innate immune gene expression profiling. For comparison, they also studied the microbiota of the intestinal mucosa of the same patients.

Compared with mucosal microbiota, the lamina propria microbiota was enriched in Proteobacteria — the “defining phyla” associated with dysbiosis in inflammatory bowel disease, the investigators wrote. Gene profiling revealed extensive functional and metabolic differences between the lamina propria microbiota and the mucosal microbiota, regardless of whether patients had Crohn’s disease or ulcerative colitis.

The microbiota associated with phagocytes was similar in inflamed and uninflamed tissue from the same patients, but it significantly differed between inflamed tissue from patients with Crohn’s disease and inflamed tissue from patients with ulcerative colitis. “These results suggest that the phagocyte-associated microbiota distinguishes Crohn’s disease and ulcerative colitis in the setting of inflammation,” the researchers wrote.

The oncostatin M (OSM) gene, which is part of the IL6 cytokine family of genes, was “highly upregulated” in inflamed CD11b+ cells from the patients, the researchers said. An adjusted analysis did not find statistically significant correlations between specific microbes and inflammatory genes, but clusters of genes were expressed at higher and lower levels in cells from inflamed versus noninflamed tissue, and these gene clusters correlated with specific bacterial genera.

“These results suggest that the variation in the abundance of specific groups of microbiota may affect gene expression levels in host lamina propria phagocyte cell types,” the researchers said. They added that their study method enabled them to “amplify and detect bacteria that are found at very low abundance in the gastrointestinal tract [and that] may participate in initiating or promoting inflammatory bowel disease.”

The study was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s & Colitis Foundation of America, Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and the Martin Kaiser Chair in Gastroenterology at the University of Miami. The senior investigator disclosed ties to Prometheus, Takeda, Pfizer, AbbVie, Janssen, and several other companies. The other researchers reported having no conflicts of interest.

SOURCE: Dheer R et al. Cell Mol Gastroenterol Hepatol. 2020. doi: 10.1016/j.jcmgh.2019.10.013.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

MAUI, HAWAII – If an intra-abdominal abscess in a recently diagnosed Crohn’s disease patient is less than 6 cm across with no downstream stenosis, involves only a short segment of bowel, and the patient has no perianal disease, then infliximab and azathioprine after drainage and antibiotics might be enough to heal it, according to Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic.

M. Alexander Otto/MDedge News

That will work in about 30% of patients who hit the mark; the rest will eventually need surgery, said Dr. Regueiro, a clinical researcher who has worked extensively with surgical GI patients and is also a coauthor on the American College of Gastroenterology 2018 Crohn’s disease guidelines (Am J Gastroenterol. 2018 Apr;113[4]:481-517).

Intra-abdominal abscesses are common in Crohn’s, usually from an inflammation-induced fistula or sinus in the small intestines that spills luminal contents into the abdominal cavity. Drainage and antibiotics are first line, but then there’s the question of who needs to go to the operating room and who doesn’t.

It has to do with “how much the hole in the intestines is actually reversible. Evidence of a stricture is of paramount importance. If you have a stricture below a fistula and prestenotic dilatation, that’s a high-pressure zone.” It’s a “fixed complication that, in my opinion, no medication is ever going to treat,” he said at the Gastroenterology Updates, IBD, Liver Disease Conference.

Most patients will need surgery, but for smaller abscesses in qualifying patients, medical treatment can work. “Infliximab is still probably the best medicine for fistulizing disease,” so Dr. Regueiro opts for that if patients haven’t been on it before, in combination with an immunomodulator, generally azathioprine at half the standard dose, to prevent patients from forming antibodies to the infliximab.

When patients do go to the operating room, there is a good chance they will end up with a temporary ostomy, and definitely so if the abscess can’t be drained completely to prevent spillage. The risk of dehiscence and other complications is too great for primary anastomosis.

“I mentally prepare my patients for that; I tell them up front. I never guarantee that they are not going to have an ostomy bag,” Dr. Regueiro said.

He also said abscess formation isn’t necessarily a sign the biologic patients were on before has failed, especially if they were only on it for 6 months or so. More likely, “the disease was too far gone at that point” for short-term treatment to have much of an effect.

So he’s often likely to continue patients on the same biologic after surgery. “We’ve done a lot of study on” this and have “actually found that” patients do well with the approach. He will switch treatment, however, if they otherwise no longer seem to respond to a biologic they have been taking a while, despite adequate serum levels.

There’s no need to delay surgery for patients on biologics. “If they get a biologic the day before, they can still go to the [operating room]. We are not seeing increased postop complications, infections, or wound dehiscence,” he said.

Dr. Regueiro generally restarts biologics 2-4 weeks after surgery, which is enough time to know if there is going to be a surgical complication but not so long that patients will have a Crohn’s relapse. He restarts the maintenance dose, as “it’s not necessary to reinduct patients after such a short break,” he said.

He also noted that opioids and steroids should be avoided with Crohn’s abscesses. Opioids increase the risk of ileus, and steroids the risk of sepsis.

Dr. Regueiro reported no relevant disclosures.

[email protected]

MAUI, HAWAII – If an intra-abdominal abscess in a recently diagnosed Crohn’s disease patient is less than 6 cm across with no downstream stenosis, involves only a short segment of bowel, and the patient has no perianal disease, then infliximab and azathioprine after drainage and antibiotics might be enough to heal it, according to Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic.

M. Alexander Otto/MDedge News

That will work in about 30% of patients who hit the mark; the rest will eventually need surgery, said Dr. Regueiro, a clinical researcher who has worked extensively with surgical GI patients and is also a coauthor on the American College of Gastroenterology 2018 Crohn’s disease guidelines (Am J Gastroenterol. 2018 Apr;113[4]:481-517).

Intra-abdominal abscesses are common in Crohn’s, usually from an inflammation-induced fistula or sinus in the small intestines that spills luminal contents into the abdominal cavity. Drainage and antibiotics are first line, but then there’s the question of who needs to go to the operating room and who doesn’t.

It has to do with “how much the hole in the intestines is actually reversible. Evidence of a stricture is of paramount importance. If you have a stricture below a fistula and prestenotic dilatation, that’s a high-pressure zone.” It’s a “fixed complication that, in my opinion, no medication is ever going to treat,” he said at the Gastroenterology Updates, IBD, Liver Disease Conference.

Most patients will need surgery, but for smaller abscesses in qualifying patients, medical treatment can work. “Infliximab is still probably the best medicine for fistulizing disease,” so Dr. Regueiro opts for that if patients haven’t been on it before, in combination with an immunomodulator, generally azathioprine at half the standard dose, to prevent patients from forming antibodies to the infliximab.

When patients do go to the operating room, there is a good chance they will end up with a temporary ostomy, and definitely so if the abscess can’t be drained completely to prevent spillage. The risk of dehiscence and other complications is too great for primary anastomosis.

“I mentally prepare my patients for that; I tell them up front. I never guarantee that they are not going to have an ostomy bag,” Dr. Regueiro said.

He also said abscess formation isn’t necessarily a sign the biologic patients were on before has failed, especially if they were only on it for 6 months or so. More likely, “the disease was too far gone at that point” for short-term treatment to have much of an effect.

So he’s often likely to continue patients on the same biologic after surgery. “We’ve done a lot of study on” this and have “actually found that” patients do well with the approach. He will switch treatment, however, if they otherwise no longer seem to respond to a biologic they have been taking a while, despite adequate serum levels.

There’s no need to delay surgery for patients on biologics. “If they get a biologic the day before, they can still go to the [operating room]. We are not seeing increased postop complications, infections, or wound dehiscence,” he said.

Dr. Regueiro generally restarts biologics 2-4 weeks after surgery, which is enough time to know if there is going to be a surgical complication but not so long that patients will have a Crohn’s relapse. He restarts the maintenance dose, as “it’s not necessary to reinduct patients after such a short break,” he said.

He also noted that opioids and steroids should be avoided with Crohn’s abscesses. Opioids increase the risk of ileus, and steroids the risk of sepsis.

Dr. Regueiro reported no relevant disclosures.

[email protected]

MAUI, HAWAII – If an intra-abdominal abscess in a recently diagnosed Crohn’s disease patient is less than 6 cm across with no downstream stenosis, involves only a short segment of bowel, and the patient has no perianal disease, then infliximab and azathioprine after drainage and antibiotics might be enough to heal it, according to Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic.

M. Alexander Otto/MDedge News

That will work in about 30% of patients who hit the mark; the rest will eventually need surgery, said Dr. Regueiro, a clinical researcher who has worked extensively with surgical GI patients and is also a coauthor on the American College of Gastroenterology 2018 Crohn’s disease guidelines (Am J Gastroenterol. 2018 Apr;113[4]:481-517).

Intra-abdominal abscesses are common in Crohn’s, usually from an inflammation-induced fistula or sinus in the small intestines that spills luminal contents into the abdominal cavity. Drainage and antibiotics are first line, but then there’s the question of who needs to go to the operating room and who doesn’t.

It has to do with “how much the hole in the intestines is actually reversible. Evidence of a stricture is of paramount importance. If you have a stricture below a fistula and prestenotic dilatation, that’s a high-pressure zone.” It’s a “fixed complication that, in my opinion, no medication is ever going to treat,” he said at the Gastroenterology Updates, IBD, Liver Disease Conference.

Most patients will need surgery, but for smaller abscesses in qualifying patients, medical treatment can work. “Infliximab is still probably the best medicine for fistulizing disease,” so Dr. Regueiro opts for that if patients haven’t been on it before, in combination with an immunomodulator, generally azathioprine at half the standard dose, to prevent patients from forming antibodies to the infliximab.

When patients do go to the operating room, there is a good chance they will end up with a temporary ostomy, and definitely so if the abscess can’t be drained completely to prevent spillage. The risk of dehiscence and other complications is too great for primary anastomosis.

“I mentally prepare my patients for that; I tell them up front. I never guarantee that they are not going to have an ostomy bag,” Dr. Regueiro said.

He also said abscess formation isn’t necessarily a sign the biologic patients were on before has failed, especially if they were only on it for 6 months or so. More likely, “the disease was too far gone at that point” for short-term treatment to have much of an effect.

So he’s often likely to continue patients on the same biologic after surgery. “We’ve done a lot of study on” this and have “actually found that” patients do well with the approach. He will switch treatment, however, if they otherwise no longer seem to respond to a biologic they have been taking a while, despite adequate serum levels.

There’s no need to delay surgery for patients on biologics. “If they get a biologic the day before, they can still go to the [operating room]. We are not seeing increased postop complications, infections, or wound dehiscence,” he said.

Dr. Regueiro generally restarts biologics 2-4 weeks after surgery, which is enough time to know if there is going to be a surgical complication but not so long that patients will have a Crohn’s relapse. He restarts the maintenance dose, as “it’s not necessary to reinduct patients after such a short break,” he said.

He also noted that opioids and steroids should be avoided with Crohn’s abscesses. Opioids increase the risk of ileus, and steroids the risk of sepsis.

Dr. Regueiro reported no relevant disclosures.

[email protected]

AUSTIN, TEX. – Patients with inflammatory bowel disease (IBD) who want to have children can benefit from better education about recent findings that disease control, laparoscopic surgery, and in vitro fertilization (IVF) have improved their chances of conceiving, according to a review of published reports presented here at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Congress Foundation and the American Gastroenterological Association.

Richard Mark Kirkner/MDedge News

“Decreased fertility in IBD is due to voluntary childlessness, which we can change with education; surgery for IBD, which we can improve with laparoscopic surgery; and increased disease activity, which we can also make a difference in,” Sonia Friedman, MD, of Harvard Medical School, Boston, said in an interview.

Dr. Friedman and coauthors last year published an analysis of the Danish National Birth Cohort, which showed women with IBD had an 28% greater relative risk of taking a year or more to get pregnant than controls without IBD, and that the relative risk was even higher in women with Crohn’s disease — 54% (Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.08.031). “We found that women with Crohn’s surgery had decreased fertility by 2.54 times greater relative risk,” she said.

“Fertility, pregnancy is the most important thing to patients,” Dr. Friedman said in an interview. “That’s what people ask me about the most. In the population of IBD patients, the onset is age 15-35, and these people are in the prime of their reproductive years.” Sexual function, known to be decreased in men and women with IBD, is also an overriding concern in these patients, she said. “There needs to be a lot more information out there about it.”

She said gastroenterologists should keep in mind that much of the evidence documenting reduced fertility after ileo-pouch anal anastomosis is dated and focused on open surgery, which caused profound scarring of the pelvis and fallopian tubes, thus hindering conception. Laparoscopic ileoanal J-pouch surgery (IPAA) has yielded much improved outcomes in women of child-bearing age, she said, citing a study late last year that reported women who had laparoscopic IPAA had a median time to pregnancy of 3.5 months versus 9 months for women who had open IPAA (Surgery. 2019;166:670-7).

“It’s really important to discuss the issues of fertility, especially for patients contemplating surgery,” Dr. Friedman said. “Emphasize that there are good outcomes with laparoscopic surgery, and they can have assisted reproductive technology [ART], or in vitro fertilization, if needed. Never withhold surgery based on fear of infertility.”

Her practice is to refer women with IBD in remission for IVF if they’ve tried to get pregnant every month for a year or more and to refer women with IBD surgery for IVF after trying to get pregnant for 6 months. Dr. Friedman coauthored two studies of the Danish National Birth Cohort of ART in women with Crohn’s disease and ulcerative colitis (UC) along with controls (Gut. 2016;65:767-76; Gut. 2017;66:556-58). “We found that women with Crohn’s and UC had a decreased chance of having a clinical pregnancy, but they had no problem carrying the pregnancy to term,” she said.

Those findings raised questions about the etiology of decreased fertility in IBD patients, which could include factors such as IVF technique, reproductive hormone and microbiome changes, or IBD medications. “How can we carry that forward to all women with IBD?” she said. Women with IBD have less chance of conceiving with each IVF treatment cycle than do women without IBD, she said. “The most interesting thing is that the reduced chance of live birth after IVF treatment in Crohn’s and UC is related to the stages of implantation and not to the ability to maintain the fetus throughout pregnancy,” she said.

Dr. Friedman has no financial relationships to disclose.

The AGA IBD Parenthood Project can help guide your patients with IBD throughout their pregnancy, from trying to conceive through postpartum care. Learn more at IBDParenthoodProject.org.

SOURCE: Friedman S. Crohn’s & Colitis Congress, Session Sp86.

AUSTIN, TEX. – Patients with inflammatory bowel disease (IBD) who want to have children can benefit from better education about recent findings that disease control, laparoscopic surgery, and in vitro fertilization (IVF) have improved their chances of conceiving, according to a review of published reports presented here at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Congress Foundation and the American Gastroenterological Association.

Richard Mark Kirkner/MDedge News

“Decreased fertility in IBD is due to voluntary childlessness, which we can change with education; surgery for IBD, which we can improve with laparoscopic surgery; and increased disease activity, which we can also make a difference in,” Sonia Friedman, MD, of Harvard Medical School, Boston, said in an interview.

Dr. Friedman and coauthors last year published an analysis of the Danish National Birth Cohort, which showed women with IBD had an 28% greater relative risk of taking a year or more to get pregnant than controls without IBD, and that the relative risk was even higher in women with Crohn’s disease — 54% (Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.08.031). “We found that women with Crohn’s surgery had decreased fertility by 2.54 times greater relative risk,” she said.

“Fertility, pregnancy is the most important thing to patients,” Dr. Friedman said in an interview. “That’s what people ask me about the most. In the population of IBD patients, the onset is age 15-35, and these people are in the prime of their reproductive years.” Sexual function, known to be decreased in men and women with IBD, is also an overriding concern in these patients, she said. “There needs to be a lot more information out there about it.”

She said gastroenterologists should keep in mind that much of the evidence documenting reduced fertility after ileo-pouch anal anastomosis is dated and focused on open surgery, which caused profound scarring of the pelvis and fallopian tubes, thus hindering conception. Laparoscopic ileoanal J-pouch surgery (IPAA) has yielded much improved outcomes in women of child-bearing age, she said, citing a study late last year that reported women who had laparoscopic IPAA had a median time to pregnancy of 3.5 months versus 9 months for women who had open IPAA (Surgery. 2019;166:670-7).

“It’s really important to discuss the issues of fertility, especially for patients contemplating surgery,” Dr. Friedman said. “Emphasize that there are good outcomes with laparoscopic surgery, and they can have assisted reproductive technology [ART], or in vitro fertilization, if needed. Never withhold surgery based on fear of infertility.”

Her practice is to refer women with IBD in remission for IVF if they’ve tried to get pregnant every month for a year or more and to refer women with IBD surgery for IVF after trying to get pregnant for 6 months. Dr. Friedman coauthored two studies of the Danish National Birth Cohort of ART in women with Crohn’s disease and ulcerative colitis (UC) along with controls (Gut. 2016;65:767-76; Gut. 2017;66:556-58). “We found that women with Crohn’s and UC had a decreased chance of having a clinical pregnancy, but they had no problem carrying the pregnancy to term,” she said.

Those findings raised questions about the etiology of decreased fertility in IBD patients, which could include factors such as IVF technique, reproductive hormone and microbiome changes, or IBD medications. “How can we carry that forward to all women with IBD?” she said. Women with IBD have less chance of conceiving with each IVF treatment cycle than do women without IBD, she said. “The most interesting thing is that the reduced chance of live birth after IVF treatment in Crohn’s and UC is related to the stages of implantation and not to the ability to maintain the fetus throughout pregnancy,” she said.

Dr. Friedman has no financial relationships to disclose.

The AGA IBD Parenthood Project can help guide your patients with IBD throughout their pregnancy, from trying to conceive through postpartum care. Learn more at IBDParenthoodProject.org.

SOURCE: Friedman S. Crohn’s & Colitis Congress, Session Sp86.

AUSTIN, TEX. – Patients with inflammatory bowel disease (IBD) who want to have children can benefit from better education about recent findings that disease control, laparoscopic surgery, and in vitro fertilization (IVF) have improved their chances of conceiving, according to a review of published reports presented here at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Congress Foundation and the American Gastroenterological Association.

Richard Mark Kirkner/MDedge News

“Decreased fertility in IBD is due to voluntary childlessness, which we can change with education; surgery for IBD, which we can improve with laparoscopic surgery; and increased disease activity, which we can also make a difference in,” Sonia Friedman, MD, of Harvard Medical School, Boston, said in an interview.

Dr. Friedman and coauthors last year published an analysis of the Danish National Birth Cohort, which showed women with IBD had an 28% greater relative risk of taking a year or more to get pregnant than controls without IBD, and that the relative risk was even higher in women with Crohn’s disease — 54% (Clin Gastroenterol Hepatol. 2019. doi: 10.1016/j.cgh.2019.08.031). “We found that women with Crohn’s surgery had decreased fertility by 2.54 times greater relative risk,” she said.

“Fertility, pregnancy is the most important thing to patients,” Dr. Friedman said in an interview. “That’s what people ask me about the most. In the population of IBD patients, the onset is age 15-35, and these people are in the prime of their reproductive years.” Sexual function, known to be decreased in men and women with IBD, is also an overriding concern in these patients, she said. “There needs to be a lot more information out there about it.”

She said gastroenterologists should keep in mind that much of the evidence documenting reduced fertility after ileo-pouch anal anastomosis is dated and focused on open surgery, which caused profound scarring of the pelvis and fallopian tubes, thus hindering conception. Laparoscopic ileoanal J-pouch surgery (IPAA) has yielded much improved outcomes in women of child-bearing age, she said, citing a study late last year that reported women who had laparoscopic IPAA had a median time to pregnancy of 3.5 months versus 9 months for women who had open IPAA (Surgery. 2019;166:670-7).

“It’s really important to discuss the issues of fertility, especially for patients contemplating surgery,” Dr. Friedman said. “Emphasize that there are good outcomes with laparoscopic surgery, and they can have assisted reproductive technology [ART], or in vitro fertilization, if needed. Never withhold surgery based on fear of infertility.”

Her practice is to refer women with IBD in remission for IVF if they’ve tried to get pregnant every month for a year or more and to refer women with IBD surgery for IVF after trying to get pregnant for 6 months. Dr. Friedman coauthored two studies of the Danish National Birth Cohort of ART in women with Crohn’s disease and ulcerative colitis (UC) along with controls (Gut. 2016;65:767-76; Gut. 2017;66:556-58). “We found that women with Crohn’s and UC had a decreased chance of having a clinical pregnancy, but they had no problem carrying the pregnancy to term,” she said.

Those findings raised questions about the etiology of decreased fertility in IBD patients, which could include factors such as IVF technique, reproductive hormone and microbiome changes, or IBD medications. “How can we carry that forward to all women with IBD?” she said. Women with IBD have less chance of conceiving with each IVF treatment cycle than do women without IBD, she said. “The most interesting thing is that the reduced chance of live birth after IVF treatment in Crohn’s and UC is related to the stages of implantation and not to the ability to maintain the fetus throughout pregnancy,” she said.

Dr. Friedman has no financial relationships to disclose.

The AGA IBD Parenthood Project can help guide your patients with IBD throughout their pregnancy, from trying to conceive through postpartum care. Learn more at IBDParenthoodProject.org.

SOURCE: Friedman S. Crohn’s & Colitis Congress, Session Sp86.