IBD & Intestinal Disorders

Kicking off the 2016 AGA Spring Postgraduate Course, this symposium encouraged attendees to embrace multidisciplinary approaches to managing patients with common gastrointestinal symptoms of nonstructural origin. My talk on “Managing the Big Four – Dyspepsia, Constipation, Diarrhea, and Abdominal Pain” reviewed the pathophysiology and management of these conditions. Thereafter, Sheila Crowe, MD, AGAF, Laurie Keefer, PhD, and Michael Camilleri, MD, AGAF, respectively, reviewed dietary approaches, psychological, and behavioral therapies, and overlooked, overused, and emerging pharmacotherapy for managing these conditions.

The clinical evaluation enables a precise symptom-based diagnosis of these conditions (e.g., dyspepsia, diarrhea-predominant irritable bowel syndrome [IBS], chronic constipation, defecatory disorders, and chronic abdominal pain). Dr. Keefer emphasized the importance of setting a pro-solution agenda early in the interview as well as listening, understanding, and believing symptoms. Empathy is essential. At the same time, patients need to assume personal responsibility and contribute to their own wellness. Expectations and a treatment plan should be negotiated. Bowel symptom questionnaires and, if necessary, bowel diaries ensure that symptoms are addressed comprehensively and save time. A meticulous digital rectal exam is essential since defecatory disorders are associated with not only lower but also upper GI symptoms. Only selected diagnostic tests, guided by the clinical features, should be performed.

Our understanding of the pathophysiology is evolving. Functional dyspepsia is implicated to impaired gastric accommodation, delayed gastric emptying, and increased gastric as well as duodenal sensitivity. Peripheral irritation (e.g., due to persistent low-grade inflammation after resolution of acute gastroenteritis or bile acids) and central dysfunctions (e.g., resulting from anxiety or depression) can alter GI transit and sensitivity resulting in IBS. Slow colon transit and impaired defecation (i.e., defecatory disorders) can cause chronic constipation.

Initially, therapy should utilize inexpensive, over-the-counter agents (loperamide for diarrhea). Dr. Camilleri also highlighted the utility of bile acid binding agents (e.g., cholestyramine and colesevelam) and when necessary, alosteron for diarrhea and cautioned attendees to use rifaximin as recommended by the Food and Drug Administration (i.e., up to three courses of 2 weeks) and not for long-term therapy. Several newer agents for these disorders are being developed. Dr. Crowe reminded the audience that foods often induce symptoms. In a recent study, a “common-sense” IBS diet was as effective as was a low-FODMAP diet for IBS. Eliminating gluten or wheat starch may benefit some patients with IBS without celiac disease but more evidence is required. Dr. Keefer highlighted the utility of diaphragmatic breathing for rumination, pelvic floor biofeedback therapy for defecatory disorders, and psychological therapies, especially cognitive behavioral therapy, for patients with a variety of GI symptoms.

Dr. Bharucha is with the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

Kicking off the 2016 AGA Spring Postgraduate Course, this symposium encouraged attendees to embrace multidisciplinary approaches to managing patients with common gastrointestinal symptoms of nonstructural origin. My talk on “Managing the Big Four – Dyspepsia, Constipation, Diarrhea, and Abdominal Pain” reviewed the pathophysiology and management of these conditions. Thereafter, Sheila Crowe, MD, AGAF, Laurie Keefer, PhD, and Michael Camilleri, MD, AGAF, respectively, reviewed dietary approaches, psychological, and behavioral therapies, and overlooked, overused, and emerging pharmacotherapy for managing these conditions.

The clinical evaluation enables a precise symptom-based diagnosis of these conditions (e.g., dyspepsia, diarrhea-predominant irritable bowel syndrome [IBS], chronic constipation, defecatory disorders, and chronic abdominal pain). Dr. Keefer emphasized the importance of setting a pro-solution agenda early in the interview as well as listening, understanding, and believing symptoms. Empathy is essential. At the same time, patients need to assume personal responsibility and contribute to their own wellness. Expectations and a treatment plan should be negotiated. Bowel symptom questionnaires and, if necessary, bowel diaries ensure that symptoms are addressed comprehensively and save time. A meticulous digital rectal exam is essential since defecatory disorders are associated with not only lower but also upper GI symptoms. Only selected diagnostic tests, guided by the clinical features, should be performed.

Our understanding of the pathophysiology is evolving. Functional dyspepsia is implicated to impaired gastric accommodation, delayed gastric emptying, and increased gastric as well as duodenal sensitivity. Peripheral irritation (e.g., due to persistent low-grade inflammation after resolution of acute gastroenteritis or bile acids) and central dysfunctions (e.g., resulting from anxiety or depression) can alter GI transit and sensitivity resulting in IBS. Slow colon transit and impaired defecation (i.e., defecatory disorders) can cause chronic constipation.

Initially, therapy should utilize inexpensive, over-the-counter agents (loperamide for diarrhea). Dr. Camilleri also highlighted the utility of bile acid binding agents (e.g., cholestyramine and colesevelam) and when necessary, alosteron for diarrhea and cautioned attendees to use rifaximin as recommended by the Food and Drug Administration (i.e., up to three courses of 2 weeks) and not for long-term therapy. Several newer agents for these disorders are being developed. Dr. Crowe reminded the audience that foods often induce symptoms. In a recent study, a “common-sense” IBS diet was as effective as was a low-FODMAP diet for IBS. Eliminating gluten or wheat starch may benefit some patients with IBS without celiac disease but more evidence is required. Dr. Keefer highlighted the utility of diaphragmatic breathing for rumination, pelvic floor biofeedback therapy for defecatory disorders, and psychological therapies, especially cognitive behavioral therapy, for patients with a variety of GI symptoms.

Dr. Bharucha is with the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

Kicking off the 2016 AGA Spring Postgraduate Course, this symposium encouraged attendees to embrace multidisciplinary approaches to managing patients with common gastrointestinal symptoms of nonstructural origin. My talk on “Managing the Big Four – Dyspepsia, Constipation, Diarrhea, and Abdominal Pain” reviewed the pathophysiology and management of these conditions. Thereafter, Sheila Crowe, MD, AGAF, Laurie Keefer, PhD, and Michael Camilleri, MD, AGAF, respectively, reviewed dietary approaches, psychological, and behavioral therapies, and overlooked, overused, and emerging pharmacotherapy for managing these conditions.

The clinical evaluation enables a precise symptom-based diagnosis of these conditions (e.g., dyspepsia, diarrhea-predominant irritable bowel syndrome [IBS], chronic constipation, defecatory disorders, and chronic abdominal pain). Dr. Keefer emphasized the importance of setting a pro-solution agenda early in the interview as well as listening, understanding, and believing symptoms. Empathy is essential. At the same time, patients need to assume personal responsibility and contribute to their own wellness. Expectations and a treatment plan should be negotiated. Bowel symptom questionnaires and, if necessary, bowel diaries ensure that symptoms are addressed comprehensively and save time. A meticulous digital rectal exam is essential since defecatory disorders are associated with not only lower but also upper GI symptoms. Only selected diagnostic tests, guided by the clinical features, should be performed.

Our understanding of the pathophysiology is evolving. Functional dyspepsia is implicated to impaired gastric accommodation, delayed gastric emptying, and increased gastric as well as duodenal sensitivity. Peripheral irritation (e.g., due to persistent low-grade inflammation after resolution of acute gastroenteritis or bile acids) and central dysfunctions (e.g., resulting from anxiety or depression) can alter GI transit and sensitivity resulting in IBS. Slow colon transit and impaired defecation (i.e., defecatory disorders) can cause chronic constipation.

Initially, therapy should utilize inexpensive, over-the-counter agents (loperamide for diarrhea). Dr. Camilleri also highlighted the utility of bile acid binding agents (e.g., cholestyramine and colesevelam) and when necessary, alosteron for diarrhea and cautioned attendees to use rifaximin as recommended by the Food and Drug Administration (i.e., up to three courses of 2 weeks) and not for long-term therapy. Several newer agents for these disorders are being developed. Dr. Crowe reminded the audience that foods often induce symptoms. In a recent study, a “common-sense” IBS diet was as effective as was a low-FODMAP diet for IBS. Eliminating gluten or wheat starch may benefit some patients with IBS without celiac disease but more evidence is required. Dr. Keefer highlighted the utility of diaphragmatic breathing for rumination, pelvic floor biofeedback therapy for defecatory disorders, and psychological therapies, especially cognitive behavioral therapy, for patients with a variety of GI symptoms.

Dr. Bharucha is with the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

A new classification tool helped guide the treatment of bacteremic patients while clinicians awaited antibiotic resistance results, investigators reported.

The clinical decision tree had a positive predictive value of 91% and a negative predictive value of 92% for determining whether certain gram-negative infections produced extended-spectrum beta-lactamase (ESBL), Catherine Goodman, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates wrote online in Clinical Infectious Diseases. “These predictions may assist empiric treatment decisions in order to optimize clinical outcomes while reducing administration of overly broad antibiotic agents that can select for further resistance emergence,” they added.

Bacteria that produce ESBL can hydrolyze all broad-spectrum beta-lactam antibiotics except carbapenems. Rapid tests for beta-lactamase genes can shorten the lag time between gram-stain identification and antimicrobial resistance results, but are cost prohibitive for most clinical laboratories and often do not assess ESBL gene groups, the researchers said. To find a way to predict which infections are characterized by ESBL production, they studied adults hospitalized at Johns Hopkins from October 2008 to March 2015 with bloodstream isolates of Klebsiella pneumoniae (40% of patients), Klebsiella oxytoca (4% of patients), and Escherichia coli (56% of patients). Most bacteremias began as urinary tract infections (34% of cases), followed by intra-abdominal infections (24%), catheter-related infections (16%), and biliary infections (14%) (Clin Infect Dis. 2016 Jul 26. doi:10.1093/cid/ciw425).

A total of 194 patients (15%) had bacteremias that produced ESBL, according to the investigators. Using a technique called binary recursive partitioning, they compared these patients with ESBL-negative patients to create a clinical decision tree based on five yes-or-no questions. The tree first asked if the patient had been colonized or infected with ESBL-producing bacteria within 6 months, and if so, whether the patient currently had an indwelling catheter. Patients meeting both criteria had a 92% chance of being ESBL positive. Patients with a recent history of ESBL but no catheter had an 81% chance of being ESBL positive if they were at least 43 years old, but a 75% chance of being ESBL negative if they were under age 43 years.

Among patients with no recent history of ESBL, the decision tree asked about hospitalization in a country with a high ESBL burden and antibiotic therapy during the past 6 months. Patients responding “yes” to both questions had a 100% chance of being ESBL positive. Patients with only the geographic risk factor had a 63% chance of being ESBL negative, and patients with neither risk factor had a 93% chance of being ESBL negative.

The decision tree detected only half of ESBL cases because there was a subgroup with no recent ESBL history or geographic exposure, the investigators noted. “The poor predictive nature of health care–associated variables within this patient subset may suggest a high proportion of community-acquired ESBL infections. Indeed, although risk factors for ESBLs have traditionally focused on the health care setting, increasing reports describe the community as an important ESBL reservoir,” they added. Nonetheless, of 194 patients with ESBL bacteremia, 35% received empiric carbapenem treatment within 6 hours after identification of the bacterial genus and species, the investigators emphasized. “Utilization of the decision tree would have increased ESBL case detection during the empiric treatment window by approximately 50%.”

The National Institutes of Health funded the study. The researchers reported having no conflicts of interest.

A new classification tool helped guide the treatment of bacteremic patients while clinicians awaited antibiotic resistance results, investigators reported.

The clinical decision tree had a positive predictive value of 91% and a negative predictive value of 92% for determining whether certain gram-negative infections produced extended-spectrum beta-lactamase (ESBL), Catherine Goodman, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates wrote online in Clinical Infectious Diseases. “These predictions may assist empiric treatment decisions in order to optimize clinical outcomes while reducing administration of overly broad antibiotic agents that can select for further resistance emergence,” they added.

Bacteria that produce ESBL can hydrolyze all broad-spectrum beta-lactam antibiotics except carbapenems. Rapid tests for beta-lactamase genes can shorten the lag time between gram-stain identification and antimicrobial resistance results, but are cost prohibitive for most clinical laboratories and often do not assess ESBL gene groups, the researchers said. To find a way to predict which infections are characterized by ESBL production, they studied adults hospitalized at Johns Hopkins from October 2008 to March 2015 with bloodstream isolates of Klebsiella pneumoniae (40% of patients), Klebsiella oxytoca (4% of patients), and Escherichia coli (56% of patients). Most bacteremias began as urinary tract infections (34% of cases), followed by intra-abdominal infections (24%), catheter-related infections (16%), and biliary infections (14%) (Clin Infect Dis. 2016 Jul 26. doi:10.1093/cid/ciw425).

A total of 194 patients (15%) had bacteremias that produced ESBL, according to the investigators. Using a technique called binary recursive partitioning, they compared these patients with ESBL-negative patients to create a clinical decision tree based on five yes-or-no questions. The tree first asked if the patient had been colonized or infected with ESBL-producing bacteria within 6 months, and if so, whether the patient currently had an indwelling catheter. Patients meeting both criteria had a 92% chance of being ESBL positive. Patients with a recent history of ESBL but no catheter had an 81% chance of being ESBL positive if they were at least 43 years old, but a 75% chance of being ESBL negative if they were under age 43 years.

Among patients with no recent history of ESBL, the decision tree asked about hospitalization in a country with a high ESBL burden and antibiotic therapy during the past 6 months. Patients responding “yes” to both questions had a 100% chance of being ESBL positive. Patients with only the geographic risk factor had a 63% chance of being ESBL negative, and patients with neither risk factor had a 93% chance of being ESBL negative.

The decision tree detected only half of ESBL cases because there was a subgroup with no recent ESBL history or geographic exposure, the investigators noted. “The poor predictive nature of health care–associated variables within this patient subset may suggest a high proportion of community-acquired ESBL infections. Indeed, although risk factors for ESBLs have traditionally focused on the health care setting, increasing reports describe the community as an important ESBL reservoir,” they added. Nonetheless, of 194 patients with ESBL bacteremia, 35% received empiric carbapenem treatment within 6 hours after identification of the bacterial genus and species, the investigators emphasized. “Utilization of the decision tree would have increased ESBL case detection during the empiric treatment window by approximately 50%.”

The National Institutes of Health funded the study. The researchers reported having no conflicts of interest.

A new classification tool helped guide the treatment of bacteremic patients while clinicians awaited antibiotic resistance results, investigators reported.

The clinical decision tree had a positive predictive value of 91% and a negative predictive value of 92% for determining whether certain gram-negative infections produced extended-spectrum beta-lactamase (ESBL), Catherine Goodman, PhD, of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and her associates wrote online in Clinical Infectious Diseases. “These predictions may assist empiric treatment decisions in order to optimize clinical outcomes while reducing administration of overly broad antibiotic agents that can select for further resistance emergence,” they added.

Bacteria that produce ESBL can hydrolyze all broad-spectrum beta-lactam antibiotics except carbapenems. Rapid tests for beta-lactamase genes can shorten the lag time between gram-stain identification and antimicrobial resistance results, but are cost prohibitive for most clinical laboratories and often do not assess ESBL gene groups, the researchers said. To find a way to predict which infections are characterized by ESBL production, they studied adults hospitalized at Johns Hopkins from October 2008 to March 2015 with bloodstream isolates of Klebsiella pneumoniae (40% of patients), Klebsiella oxytoca (4% of patients), and Escherichia coli (56% of patients). Most bacteremias began as urinary tract infections (34% of cases), followed by intra-abdominal infections (24%), catheter-related infections (16%), and biliary infections (14%) (Clin Infect Dis. 2016 Jul 26. doi:10.1093/cid/ciw425).

A total of 194 patients (15%) had bacteremias that produced ESBL, according to the investigators. Using a technique called binary recursive partitioning, they compared these patients with ESBL-negative patients to create a clinical decision tree based on five yes-or-no questions. The tree first asked if the patient had been colonized or infected with ESBL-producing bacteria within 6 months, and if so, whether the patient currently had an indwelling catheter. Patients meeting both criteria had a 92% chance of being ESBL positive. Patients with a recent history of ESBL but no catheter had an 81% chance of being ESBL positive if they were at least 43 years old, but a 75% chance of being ESBL negative if they were under age 43 years.

Among patients with no recent history of ESBL, the decision tree asked about hospitalization in a country with a high ESBL burden and antibiotic therapy during the past 6 months. Patients responding “yes” to both questions had a 100% chance of being ESBL positive. Patients with only the geographic risk factor had a 63% chance of being ESBL negative, and patients with neither risk factor had a 93% chance of being ESBL negative.

The decision tree detected only half of ESBL cases because there was a subgroup with no recent ESBL history or geographic exposure, the investigators noted. “The poor predictive nature of health care–associated variables within this patient subset may suggest a high proportion of community-acquired ESBL infections. Indeed, although risk factors for ESBLs have traditionally focused on the health care setting, increasing reports describe the community as an important ESBL reservoir,” they added. Nonetheless, of 194 patients with ESBL bacteremia, 35% received empiric carbapenem treatment within 6 hours after identification of the bacterial genus and species, the investigators emphasized. “Utilization of the decision tree would have increased ESBL case detection during the empiric treatment window by approximately 50%.”

The National Institutes of Health funded the study. The researchers reported having no conflicts of interest.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

For patients with recurrent Clostridium difficile infection (CDI), donor stool administered via colonoscopy seemed safe and achieved clinical cure significantly more often than autologous fecal microbiota transplantation (FMT), based on a small trial reported online in Annals of Internal Medicine.

In all, 20 of 22 patients (91%) achieved cure with donor FMT, compared with 63% of patients who received their own markedly dysbiotic stool (P = .04), reported Colleen Kelly, MD, of The Miriam Hospital, Providence, R.I., together with her associates. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates,” the researchers wrote.

FMT corrects the dysbiosis associated with CDI and is recommended in the event of failed antibiotic therapy leading to a third episode of infection. But this advice is based mainly on case series and open-label trials, the researchers noted. Their dual-center, randomized, controlled, double-blinded study included 46 patients with at least three recurrences of CDI who had completed a course of vancomycin during their most recent episode of infection. Patients older than age 75 years or who were immunocompromised were excluded (Ann Intern Med. 2016 Aug 22. doi: 10.7326/M16-0271).

The overall clinical cure rates reflected the literature, the researchers reported, and all nine patients who developed CDI after autologous FMT were subsequently cured by donor FMT. Indeed, donor FMT “restored normal microbial community structure, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes. In contrast, microbial diversity did not improve after autologous FMT.”

Notably, however, 90% of autologous FMT patients at the center in New York achieved clinical cure, compared with 43% of patients at the center in Rhode Island. Further analyses revealed differences between patients and fecal microbiota at the two sites, the investigators said. Patients in New York typically had CDI for longer, with more recurrences and up to 148 weeks of vancomycin and other antibiotics. Thus, they might have been cured before enrollment. But “autologous FMT patients at the New York site [also] had greater abundances of Clostridia, raising the possibility of emergence of microbial community assemblages inhibitory to C. difficile via competitive niche exclusion, or possibly by emergence of nontoxigenic organisms,” the researchers wrote.

There were no serious adverse effects associated with either type of FMT, they noted.

Dr. Kelly disclosed ties to Seres Health outside the submitted work. Two coauthors had patents or patents pending for “compositions and methods for transplantation of colon microbiota.” A third coauthor disclosed ties to OpenBiome and personal fees from CIPAC/Crestovo outside the submitted work. The remaining coauthors had no conflicts of interest.

Celiac disease’s only treatment is far from ideal. Not only is the gluten-free diet hard to follow, costly, and socially isolating, but even adherent patients can suffer persistent and disabling symptoms, Daniel A. Leffler, MD, MS, of Beth Israel Deaconess Medical Center in Boston, and his associates noted. This “high unmet medical need” inspired their discussion of clinical trials in celiac disease at the third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics (GREAT 3). A summary appears as a Clinical Practice Update in Gastroenterology (2016 Jul 22. doi: 10.1053/j.gastro.2016.07.025).

Celiac is the “outlier among intestinal diseases,” the experts noted. Few randomized trials have assessed nondietary celiac disease therapies, drug developers lack a precedent approval to clarify a “guiding regulatory pathway.” The first step toward bridging these gaps is to better define target populations for clinical trials, meeting attendees agreed. Such groups might include patients with diet-refractory symptoms; newly diagnosed patients who need pharmacologic support for symptom resolution and duodenal healing; patients with asymptomatic mucosal damage, if such damage is shown to cause malignancy; and patients with neurobehavioral disorders that impede gluten avoidance. Medications that enable patients to safely consume gluten could benefit even more, including those who already face “arduous” dietary controls from comorbidities such as type 1 diabetes, the experts added.

Defining “clinical benefit” in pivotal trials of celiac disease also poses a challenge. “While every patient might desire something slightly different, the overarching theme of clinical benefit from the patient’s perspective appears to be quality of life – free of symptoms and inflammation without worry about [gluten] contamination,” attendees emphasized. Indeed, one recent survey found that patients prioritized protection against cross-contamination over being able to consume gluten at will. But initial trials should focus on gastrointestinal symptoms, which are common, affect patients of all ages, and “can be measured in a reasonable time frame,” they concluded.

Unfortunately, defining and measuring atypical symptoms can be difficult, particularly in children and adolescents. In an unpublished study at the Nationwide Children’s Hospital, gastrointestinal symptoms affected 77% of celiac patients, while only about 5% experienced atypical or nongastrointestinal symptoms, the experts noted. Such low percentages could make it difficult to adequately power studies of these nongastrointestinal outcomes. Furthermore, measuring sequelae such as osteoporosis or anemia “would require longer studies, as these conditions do not resolve quickly.”

Phase II and III trials cannot secure marketing approvals without clearly defining and measuring “clinical benefit,” Food and Drug Administration representatives at the meeting noted. Accordingly, diarrhea and abdominal pain will be key patient-reported outcome measures, and pivotal trials of young children with celiac disease will require observer-reported outcomes, attendees agreed. Although both celiac disease and the gluten-free diet profoundly undercut health-related quality of life, this measure is too broad and easily confounded to be a good endpoint in pivotal trials of celiac therapies. Likewise, histology is valuable for relating symptoms to active disease, but mucosal healing is too variable and unpredictable to serve as a primary endpoint, experts noted.

In contrast, serologic tests could serve as enrollment criteria, stratification measures, and endpoints if these tests received the appropriate FDA approvals, experts asserted. The endomysial antibody, tissue transglutaminase antibody, and deamidated gliadin peptide tests are most often used in practice, but have only been approved for diagnosing celiac disease – not as a replacement for biopsy or as a measure of disease progression or therapeutic response, FDA representatives noted. Although drug developers need tools to measure therapeutic efficacy in celiac disease, FDA recommended soliciting advice from its Center for Drug Evaluation and Research before testing these tools or kicking off monitoring studies.

The meeting was supported by the Celiac Disease Foundation and Beyond Celiac, and was sponsored by the FDA Center for Drug Evaluation and Research; the American Gastroenterological Association; the American College of Gastroenterology; the American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; and the North American Society for the Study of Celiac Disease. Dr. Leffler disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, INOVA Diagnostics, Coronado Biosciences, Pfizer, and GI Supply. One coauthor and senior author, Dr. Sheila Crowe, disclosed ties to Alvine Pharmaceuticals, Ferring, and Celimmune.

Celiac disease’s only treatment is far from ideal. Not only is the gluten-free diet hard to follow, costly, and socially isolating, but even adherent patients can suffer persistent and disabling symptoms, Daniel A. Leffler, MD, MS, of Beth Israel Deaconess Medical Center in Boston, and his associates noted. This “high unmet medical need” inspired their discussion of clinical trials in celiac disease at the third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics (GREAT 3). A summary appears as a Clinical Practice Update in Gastroenterology (2016 Jul 22. doi: 10.1053/j.gastro.2016.07.025).

Celiac is the “outlier among intestinal diseases,” the experts noted. Few randomized trials have assessed nondietary celiac disease therapies, drug developers lack a precedent approval to clarify a “guiding regulatory pathway.” The first step toward bridging these gaps is to better define target populations for clinical trials, meeting attendees agreed. Such groups might include patients with diet-refractory symptoms; newly diagnosed patients who need pharmacologic support for symptom resolution and duodenal healing; patients with asymptomatic mucosal damage, if such damage is shown to cause malignancy; and patients with neurobehavioral disorders that impede gluten avoidance. Medications that enable patients to safely consume gluten could benefit even more, including those who already face “arduous” dietary controls from comorbidities such as type 1 diabetes, the experts added.

Defining “clinical benefit” in pivotal trials of celiac disease also poses a challenge. “While every patient might desire something slightly different, the overarching theme of clinical benefit from the patient’s perspective appears to be quality of life – free of symptoms and inflammation without worry about [gluten] contamination,” attendees emphasized. Indeed, one recent survey found that patients prioritized protection against cross-contamination over being able to consume gluten at will. But initial trials should focus on gastrointestinal symptoms, which are common, affect patients of all ages, and “can be measured in a reasonable time frame,” they concluded.

Unfortunately, defining and measuring atypical symptoms can be difficult, particularly in children and adolescents. In an unpublished study at the Nationwide Children’s Hospital, gastrointestinal symptoms affected 77% of celiac patients, while only about 5% experienced atypical or nongastrointestinal symptoms, the experts noted. Such low percentages could make it difficult to adequately power studies of these nongastrointestinal outcomes. Furthermore, measuring sequelae such as osteoporosis or anemia “would require longer studies, as these conditions do not resolve quickly.”

Phase II and III trials cannot secure marketing approvals without clearly defining and measuring “clinical benefit,” Food and Drug Administration representatives at the meeting noted. Accordingly, diarrhea and abdominal pain will be key patient-reported outcome measures, and pivotal trials of young children with celiac disease will require observer-reported outcomes, attendees agreed. Although both celiac disease and the gluten-free diet profoundly undercut health-related quality of life, this measure is too broad and easily confounded to be a good endpoint in pivotal trials of celiac therapies. Likewise, histology is valuable for relating symptoms to active disease, but mucosal healing is too variable and unpredictable to serve as a primary endpoint, experts noted.

In contrast, serologic tests could serve as enrollment criteria, stratification measures, and endpoints if these tests received the appropriate FDA approvals, experts asserted. The endomysial antibody, tissue transglutaminase antibody, and deamidated gliadin peptide tests are most often used in practice, but have only been approved for diagnosing celiac disease – not as a replacement for biopsy or as a measure of disease progression or therapeutic response, FDA representatives noted. Although drug developers need tools to measure therapeutic efficacy in celiac disease, FDA recommended soliciting advice from its Center for Drug Evaluation and Research before testing these tools or kicking off monitoring studies.

The meeting was supported by the Celiac Disease Foundation and Beyond Celiac, and was sponsored by the FDA Center for Drug Evaluation and Research; the American Gastroenterological Association; the American College of Gastroenterology; the American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; and the North American Society for the Study of Celiac Disease. Dr. Leffler disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, INOVA Diagnostics, Coronado Biosciences, Pfizer, and GI Supply. One coauthor and senior author, Dr. Sheila Crowe, disclosed ties to Alvine Pharmaceuticals, Ferring, and Celimmune.

Celiac disease’s only treatment is far from ideal. Not only is the gluten-free diet hard to follow, costly, and socially isolating, but even adherent patients can suffer persistent and disabling symptoms, Daniel A. Leffler, MD, MS, of Beth Israel Deaconess Medical Center in Boston, and his associates noted. This “high unmet medical need” inspired their discussion of clinical trials in celiac disease at the third Gastroenterology Regulatory Endpoints and Advancement of Therapeutics (GREAT 3). A summary appears as a Clinical Practice Update in Gastroenterology (2016 Jul 22. doi: 10.1053/j.gastro.2016.07.025).

Celiac is the “outlier among intestinal diseases,” the experts noted. Few randomized trials have assessed nondietary celiac disease therapies, drug developers lack a precedent approval to clarify a “guiding regulatory pathway.” The first step toward bridging these gaps is to better define target populations for clinical trials, meeting attendees agreed. Such groups might include patients with diet-refractory symptoms; newly diagnosed patients who need pharmacologic support for symptom resolution and duodenal healing; patients with asymptomatic mucosal damage, if such damage is shown to cause malignancy; and patients with neurobehavioral disorders that impede gluten avoidance. Medications that enable patients to safely consume gluten could benefit even more, including those who already face “arduous” dietary controls from comorbidities such as type 1 diabetes, the experts added.

Defining “clinical benefit” in pivotal trials of celiac disease also poses a challenge. “While every patient might desire something slightly different, the overarching theme of clinical benefit from the patient’s perspective appears to be quality of life – free of symptoms and inflammation without worry about [gluten] contamination,” attendees emphasized. Indeed, one recent survey found that patients prioritized protection against cross-contamination over being able to consume gluten at will. But initial trials should focus on gastrointestinal symptoms, which are common, affect patients of all ages, and “can be measured in a reasonable time frame,” they concluded.

Unfortunately, defining and measuring atypical symptoms can be difficult, particularly in children and adolescents. In an unpublished study at the Nationwide Children’s Hospital, gastrointestinal symptoms affected 77% of celiac patients, while only about 5% experienced atypical or nongastrointestinal symptoms, the experts noted. Such low percentages could make it difficult to adequately power studies of these nongastrointestinal outcomes. Furthermore, measuring sequelae such as osteoporosis or anemia “would require longer studies, as these conditions do not resolve quickly.”

Phase II and III trials cannot secure marketing approvals without clearly defining and measuring “clinical benefit,” Food and Drug Administration representatives at the meeting noted. Accordingly, diarrhea and abdominal pain will be key patient-reported outcome measures, and pivotal trials of young children with celiac disease will require observer-reported outcomes, attendees agreed. Although both celiac disease and the gluten-free diet profoundly undercut health-related quality of life, this measure is too broad and easily confounded to be a good endpoint in pivotal trials of celiac therapies. Likewise, histology is valuable for relating symptoms to active disease, but mucosal healing is too variable and unpredictable to serve as a primary endpoint, experts noted.

In contrast, serologic tests could serve as enrollment criteria, stratification measures, and endpoints if these tests received the appropriate FDA approvals, experts asserted. The endomysial antibody, tissue transglutaminase antibody, and deamidated gliadin peptide tests are most often used in practice, but have only been approved for diagnosing celiac disease – not as a replacement for biopsy or as a measure of disease progression or therapeutic response, FDA representatives noted. Although drug developers need tools to measure therapeutic efficacy in celiac disease, FDA recommended soliciting advice from its Center for Drug Evaluation and Research before testing these tools or kicking off monitoring studies.

The meeting was supported by the Celiac Disease Foundation and Beyond Celiac, and was sponsored by the FDA Center for Drug Evaluation and Research; the American Gastroenterological Association; the American College of Gastroenterology; the American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; and the North American Society for the Study of Celiac Disease. Dr. Leffler disclosed ties to Alba Therapeutics, Alvine Pharmaceuticals, INOVA Diagnostics, Coronado Biosciences, Pfizer, and GI Supply. One coauthor and senior author, Dr. Sheila Crowe, disclosed ties to Alvine Pharmaceuticals, Ferring, and Celimmune.

SAN DIEGO – Multihospital collaboration and implementation of enhanced recovery have the potential to improve outcomes, in particular, length of hospital stay, results from a pilot study showed.

“Given the importance of patient engagement, enhanced recovery has the potential to improve patient experience and provide high-value health care,” Julia R. Berian, MD, said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

Dr. Berian, the James C. Thompson Geriatric Surgery Research Fellow at the University of Chicago Medical Center, presented findings from the Enhanced Recovery in NSQIP (ERIN) Pilot, a collaborative effort by 16 ACS-NSQIP hospitals to improve length of stay in patients who undergo colectomy, a procedure that has been shown to have an adverse event rate of 28.9% and an average length of stay of 9.8 days for those who experience an adverse event (J Am Coll Surg. 2008; 207[5]:698-704).

Implementation of the ERIN Pilot showed reductions in length of hospital stay and morbidity among colectomy patients. The average length of stay decreased by 1.2 days (from a mean of 6.6 among preimplementation cases to 5.4 days among post implementation cases; P less than .0001). Morbidity also decreased from 14% to 11% (P = .01), but the rate of readmission was 11% for both pre- and postimplementation cases. In the adjusted model, the enhanced recovery protocol decreased the risk of prolonged length of stay by 40% (odds ratio, 0.6; 95% confidence interval, 0.5-0.8).

For the ERIN Pilot, she and her associates participated in monthly conference calls for collaborative experience and expert guidance from project leaders Julie Thacker, MD, and Liane Feldman, MD. Enhanced recovery protocols were tailored to each individual hospital. Data were collected before and after implementation using 14 novel ERIN variables, including preoperative elements such as defining expectations and minimizing starvation, intraoperative variables such as optimizing fluid management and minimizing surgical trauma, and postoperative elements such as aggressive adherence to best practices including feeding, early ambulation, and minimizing the use of tethers such as urinary catheters.

The researchers evaluated procedure-targeted colectomy cases performed between July 2013 and June 2015, and excluded emergency cases or those with preoperative sepsis. They used bivariate analysis and multivariate logistic regression with forward selection, and the outcome of interest, prolonged hospital length of stay, was specified by the standard ACS NSQIP definition: greater than the 75th percentile of uncomplicated cases.

Dr. Berian reported results from 2,523 colectomies performed prior to implementation of the ERIN Pilot process and 823 colectomies performed after implementation of the process. The researchers observed no differences between the preimplementation and postimplementation cases in terms of sex, preoperative functional status, hypertension, renal failure, ascites, diabetes, disseminated cancer, or use of steroids for inflammatory bowel disease. However, compared with preimplementation colectomies, a significantly higher proportion of postimplementation cases were white (77% vs. 68%, respectively), had heart failure (2.8% vs. 1.2%), had chronic obstructive pulmonary disease (7.8% vs. 5.3%), were American Society of Anesthesiologists (ASA) class 1 and 2 ( 50.2% vs. 44.7%), were smokers (21.6% vs. 16.7%), had unintentional weight loss (7.7% vs. 5.7%), had used mechanical bowel prep (77% vs. 53%), and used more oral antibiotics (68% vs. 33%).

On the other hand, compared with preimplementation cases, there were significantly fewer bleeding disorders in the postimplementation colectomies (3.9% vs. 6.4%), as well as fewer cases with preoperative systemic inflammatory response syndrome (2.9% vs. 5.4%) and open surgery approaches (31.7% vs. 42.3%).

Dr. Berian disclosed that her fellowship position is funded by the John A. Hartford Foundation.

dbrunk@frontlinemedcom.com

SAN DIEGO – Multihospital collaboration and implementation of enhanced recovery have the potential to improve outcomes, in particular, length of hospital stay, results from a pilot study showed.

“Given the importance of patient engagement, enhanced recovery has the potential to improve patient experience and provide high-value health care,” Julia R. Berian, MD, said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

Dr. Berian, the James C. Thompson Geriatric Surgery Research Fellow at the University of Chicago Medical Center, presented findings from the Enhanced Recovery in NSQIP (ERIN) Pilot, a collaborative effort by 16 ACS-NSQIP hospitals to improve length of stay in patients who undergo colectomy, a procedure that has been shown to have an adverse event rate of 28.9% and an average length of stay of 9.8 days for those who experience an adverse event (J Am Coll Surg. 2008; 207[5]:698-704).

Implementation of the ERIN Pilot showed reductions in length of hospital stay and morbidity among colectomy patients. The average length of stay decreased by 1.2 days (from a mean of 6.6 among preimplementation cases to 5.4 days among post implementation cases; P less than .0001). Morbidity also decreased from 14% to 11% (P = .01), but the rate of readmission was 11% for both pre- and postimplementation cases. In the adjusted model, the enhanced recovery protocol decreased the risk of prolonged length of stay by 40% (odds ratio, 0.6; 95% confidence interval, 0.5-0.8).

For the ERIN Pilot, she and her associates participated in monthly conference calls for collaborative experience and expert guidance from project leaders Julie Thacker, MD, and Liane Feldman, MD. Enhanced recovery protocols were tailored to each individual hospital. Data were collected before and after implementation using 14 novel ERIN variables, including preoperative elements such as defining expectations and minimizing starvation, intraoperative variables such as optimizing fluid management and minimizing surgical trauma, and postoperative elements such as aggressive adherence to best practices including feeding, early ambulation, and minimizing the use of tethers such as urinary catheters.

The researchers evaluated procedure-targeted colectomy cases performed between July 2013 and June 2015, and excluded emergency cases or those with preoperative sepsis. They used bivariate analysis and multivariate logistic regression with forward selection, and the outcome of interest, prolonged hospital length of stay, was specified by the standard ACS NSQIP definition: greater than the 75th percentile of uncomplicated cases.

Dr. Berian reported results from 2,523 colectomies performed prior to implementation of the ERIN Pilot process and 823 colectomies performed after implementation of the process. The researchers observed no differences between the preimplementation and postimplementation cases in terms of sex, preoperative functional status, hypertension, renal failure, ascites, diabetes, disseminated cancer, or use of steroids for inflammatory bowel disease. However, compared with preimplementation colectomies, a significantly higher proportion of postimplementation cases were white (77% vs. 68%, respectively), had heart failure (2.8% vs. 1.2%), had chronic obstructive pulmonary disease (7.8% vs. 5.3%), were American Society of Anesthesiologists (ASA) class 1 and 2 ( 50.2% vs. 44.7%), were smokers (21.6% vs. 16.7%), had unintentional weight loss (7.7% vs. 5.7%), had used mechanical bowel prep (77% vs. 53%), and used more oral antibiotics (68% vs. 33%).

On the other hand, compared with preimplementation cases, there were significantly fewer bleeding disorders in the postimplementation colectomies (3.9% vs. 6.4%), as well as fewer cases with preoperative systemic inflammatory response syndrome (2.9% vs. 5.4%) and open surgery approaches (31.7% vs. 42.3%).

Dr. Berian disclosed that her fellowship position is funded by the John A. Hartford Foundation.

dbrunk@frontlinemedcom.com

SAN DIEGO – Multihospital collaboration and implementation of enhanced recovery have the potential to improve outcomes, in particular, length of hospital stay, results from a pilot study showed.

“Given the importance of patient engagement, enhanced recovery has the potential to improve patient experience and provide high-value health care,” Julia R. Berian, MD, said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

Dr. Berian, the James C. Thompson Geriatric Surgery Research Fellow at the University of Chicago Medical Center, presented findings from the Enhanced Recovery in NSQIP (ERIN) Pilot, a collaborative effort by 16 ACS-NSQIP hospitals to improve length of stay in patients who undergo colectomy, a procedure that has been shown to have an adverse event rate of 28.9% and an average length of stay of 9.8 days for those who experience an adverse event (J Am Coll Surg. 2008; 207[5]:698-704).

Implementation of the ERIN Pilot showed reductions in length of hospital stay and morbidity among colectomy patients. The average length of stay decreased by 1.2 days (from a mean of 6.6 among preimplementation cases to 5.4 days among post implementation cases; P less than .0001). Morbidity also decreased from 14% to 11% (P = .01), but the rate of readmission was 11% for both pre- and postimplementation cases. In the adjusted model, the enhanced recovery protocol decreased the risk of prolonged length of stay by 40% (odds ratio, 0.6; 95% confidence interval, 0.5-0.8).

For the ERIN Pilot, she and her associates participated in monthly conference calls for collaborative experience and expert guidance from project leaders Julie Thacker, MD, and Liane Feldman, MD. Enhanced recovery protocols were tailored to each individual hospital. Data were collected before and after implementation using 14 novel ERIN variables, including preoperative elements such as defining expectations and minimizing starvation, intraoperative variables such as optimizing fluid management and minimizing surgical trauma, and postoperative elements such as aggressive adherence to best practices including feeding, early ambulation, and minimizing the use of tethers such as urinary catheters.

The researchers evaluated procedure-targeted colectomy cases performed between July 2013 and June 2015, and excluded emergency cases or those with preoperative sepsis. They used bivariate analysis and multivariate logistic regression with forward selection, and the outcome of interest, prolonged hospital length of stay, was specified by the standard ACS NSQIP definition: greater than the 75th percentile of uncomplicated cases.

Dr. Berian reported results from 2,523 colectomies performed prior to implementation of the ERIN Pilot process and 823 colectomies performed after implementation of the process. The researchers observed no differences between the preimplementation and postimplementation cases in terms of sex, preoperative functional status, hypertension, renal failure, ascites, diabetes, disseminated cancer, or use of steroids for inflammatory bowel disease. However, compared with preimplementation colectomies, a significantly higher proportion of postimplementation cases were white (77% vs. 68%, respectively), had heart failure (2.8% vs. 1.2%), had chronic obstructive pulmonary disease (7.8% vs. 5.3%), were American Society of Anesthesiologists (ASA) class 1 and 2 ( 50.2% vs. 44.7%), were smokers (21.6% vs. 16.7%), had unintentional weight loss (7.7% vs. 5.7%), had used mechanical bowel prep (77% vs. 53%), and used more oral antibiotics (68% vs. 33%).

On the other hand, compared with preimplementation cases, there were significantly fewer bleeding disorders in the postimplementation colectomies (3.9% vs. 6.4%), as well as fewer cases with preoperative systemic inflammatory response syndrome (2.9% vs. 5.4%) and open surgery approaches (31.7% vs. 42.3%).

Dr. Berian disclosed that her fellowship position is funded by the John A. Hartford Foundation.

dbrunk@frontlinemedcom.com

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

AGA resource
The AGA Center for Gut Microbiome Research and Education was created to serve as a virtual “home” for AGA activities related to the gut microbiome. The center is focused on advancing gut microbiome research, educating AGA members and other stakeholders on the latest microbiome breakthroughs, and working with FDA and others to ensure that emerging microbiome-based treatments are safe and appropriately evaluated. Learn more here.

dchitnis@frontlinemedcom.com

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

AGA resource
The AGA Center for Gut Microbiome Research and Education was created to serve as a virtual “home” for AGA activities related to the gut microbiome. The center is focused on advancing gut microbiome research, educating AGA members and other stakeholders on the latest microbiome breakthroughs, and working with FDA and others to ensure that emerging microbiome-based treatments are safe and appropriately evaluated. Learn more here.

dchitnis@frontlinemedcom.com

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

AGA resource
The AGA Center for Gut Microbiome Research and Education was created to serve as a virtual “home” for AGA activities related to the gut microbiome. The center is focused on advancing gut microbiome research, educating AGA members and other stakeholders on the latest microbiome breakthroughs, and working with FDA and others to ensure that emerging microbiome-based treatments are safe and appropriately evaluated. Learn more here.

dchitnis@frontlinemedcom.com

Americans from the Punjab region of India had the highest prevalence of celiac disease in a national cross-sectional study of duodenal mucosal biopsies according to a study reported in the August issue of Clinical Gastroenterology and Hepatology.

In contrast, persons of South Asian, East Asian, and Hispanic descent are significantly less likely to receive a biopsy-based diagnosis of celiac disease than were other Americans, Anna Krigel, MD, at Columbia University, New York, reported with her associates. The prevalence of celiac disease among Jewish and Middle Eastern individuals resembled that of other Americans and did not differ by sex, the researchers added. “These findings may have clinical relevance to gastroenterologists across the United States and may aid in their diagnostic practices.”

Dr. Krigel and her associates analyzed a national laboratory pathology registry of 454,885 patients who underwent esophagogastroduodenoscopy with duodenal biopsy between January 2008 and April 2015. Mucosal biopsy specimens were analyzed at three laboratories by histopathologists who had completed fellowships in gastrointestinal pathology. Patients were categorized based on their first and last names as North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, or as “other Americans,” using a published algorithm. The researchers further validated this algorithm by adjusting it against a list of individuals of known ethnicities until its specificity reached 95%. Two-thirds of patients in the cohort were female, and the median age was 53 years (Clin Gastroenterol Hepatol. 2016 May 31. doi: 10.1016/j.cgh.2016.04.032).

Overall, 7,928 patients (1.7%) had duodenal villous atrophy indicative of disease, including 2% of North Indians, 1.8% of Jewish individuals, 1.8% of other Americans, 1.5% of Middle Easterners, 1.1% of Hispanics, and 0.15% of East Asians, said the investigators. Thus, Jewish persons and Middle Eastern persons had a prevalence of celiac disease similar to that of other Americans. Prevalence also was similar among Ashkenazi and Sephardic Jews. In contrast, none of the 177 South Indians in the study were diagnosed with celiac disease, and both East Asians and Hispanics were significantly less likely to be receive a diagnosis than other Americans, with odds ratios of 0.08 (95% confidence interval, 0.04-0.17) and 0.58 (0.52-0.64), respectively, and P values less than .0001.

Importantly, celiac disease was significantly more common among patients from the Punjab region of India (3.1%) than among other North Indians (1.5%; P = .02). Past studies of celiac disease in India reported similar prevalences of compatible human leukocyte antigen (HLA) haplotypes as in Western countries, without notable regional trends within India, the researchers noted. Substantial regional variations in wheat consumption in India are more likely to explain their findings and patterns of case reports in past studies, they added.

Because the registry lacked serology data, patients diagnosed with celiac disease could have actually had tropical sprue or sprue-like enteropathy due to olmesartan, the researchers acknowledged. “In particular, multiple studies have shown that tropical sprue is still the most common cause of malabsorption syndrome in India, whereas celiac disease is emerging as a more important cause of malabsorption than previously thought,” they said. “However, such cases of tropical sprue and sprue-like enteropathy due to olmesartan are far less common than celiac disease in the United States.” The study also did not account for patients whose celiac disease only was diagnosed by serology and clinical symptoms, and the algorithm probably assigned some individuals who were Hispanic to other ethnicities, because only 7% of the cohort was classified as Hispanic, compared with about 16% of Americans in the 2010 U.S. Census, they noted. But ethnic misclassification was unlikely to have differed by celiac disease status, they said.

The National Institutes of Health partially supported the work. The authors had no disclosures.

Americans from the Punjab region of India had the highest prevalence of celiac disease in a national cross-sectional study of duodenal mucosal biopsies according to a study reported in the August issue of Clinical Gastroenterology and Hepatology.

In contrast, persons of South Asian, East Asian, and Hispanic descent are significantly less likely to receive a biopsy-based diagnosis of celiac disease than were other Americans, Anna Krigel, MD, at Columbia University, New York, reported with her associates. The prevalence of celiac disease among Jewish and Middle Eastern individuals resembled that of other Americans and did not differ by sex, the researchers added. “These findings may have clinical relevance to gastroenterologists across the United States and may aid in their diagnostic practices.”

Dr. Krigel and her associates analyzed a national laboratory pathology registry of 454,885 patients who underwent esophagogastroduodenoscopy with duodenal biopsy between January 2008 and April 2015. Mucosal biopsy specimens were analyzed at three laboratories by histopathologists who had completed fellowships in gastrointestinal pathology. Patients were categorized based on their first and last names as North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, or as “other Americans,” using a published algorithm. The researchers further validated this algorithm by adjusting it against a list of individuals of known ethnicities until its specificity reached 95%. Two-thirds of patients in the cohort were female, and the median age was 53 years (Clin Gastroenterol Hepatol. 2016 May 31. doi: 10.1016/j.cgh.2016.04.032).

Overall, 7,928 patients (1.7%) had duodenal villous atrophy indicative of disease, including 2% of North Indians, 1.8% of Jewish individuals, 1.8% of other Americans, 1.5% of Middle Easterners, 1.1% of Hispanics, and 0.15% of East Asians, said the investigators. Thus, Jewish persons and Middle Eastern persons had a prevalence of celiac disease similar to that of other Americans. Prevalence also was similar among Ashkenazi and Sephardic Jews. In contrast, none of the 177 South Indians in the study were diagnosed with celiac disease, and both East Asians and Hispanics were significantly less likely to be receive a diagnosis than other Americans, with odds ratios of 0.08 (95% confidence interval, 0.04-0.17) and 0.58 (0.52-0.64), respectively, and P values less than .0001.

Importantly, celiac disease was significantly more common among patients from the Punjab region of India (3.1%) than among other North Indians (1.5%; P = .02). Past studies of celiac disease in India reported similar prevalences of compatible human leukocyte antigen (HLA) haplotypes as in Western countries, without notable regional trends within India, the researchers noted. Substantial regional variations in wheat consumption in India are more likely to explain their findings and patterns of case reports in past studies, they added.

Because the registry lacked serology data, patients diagnosed with celiac disease could have actually had tropical sprue or sprue-like enteropathy due to olmesartan, the researchers acknowledged. “In particular, multiple studies have shown that tropical sprue is still the most common cause of malabsorption syndrome in India, whereas celiac disease is emerging as a more important cause of malabsorption than previously thought,” they said. “However, such cases of tropical sprue and sprue-like enteropathy due to olmesartan are far less common than celiac disease in the United States.” The study also did not account for patients whose celiac disease only was diagnosed by serology and clinical symptoms, and the algorithm probably assigned some individuals who were Hispanic to other ethnicities, because only 7% of the cohort was classified as Hispanic, compared with about 16% of Americans in the 2010 U.S. Census, they noted. But ethnic misclassification was unlikely to have differed by celiac disease status, they said.

The National Institutes of Health partially supported the work. The authors had no disclosures.

Americans from the Punjab region of India had the highest prevalence of celiac disease in a national cross-sectional study of duodenal mucosal biopsies according to a study reported in the August issue of Clinical Gastroenterology and Hepatology.

In contrast, persons of South Asian, East Asian, and Hispanic descent are significantly less likely to receive a biopsy-based diagnosis of celiac disease than were other Americans, Anna Krigel, MD, at Columbia University, New York, reported with her associates. The prevalence of celiac disease among Jewish and Middle Eastern individuals resembled that of other Americans and did not differ by sex, the researchers added. “These findings may have clinical relevance to gastroenterologists across the United States and may aid in their diagnostic practices.”

Dr. Krigel and her associates analyzed a national laboratory pathology registry of 454,885 patients who underwent esophagogastroduodenoscopy with duodenal biopsy between January 2008 and April 2015. Mucosal biopsy specimens were analyzed at three laboratories by histopathologists who had completed fellowships in gastrointestinal pathology. Patients were categorized based on their first and last names as North Indian, South Indian, East Asian, Hispanic, Middle Eastern, Jewish, or as “other Americans,” using a published algorithm. The researchers further validated this algorithm by adjusting it against a list of individuals of known ethnicities until its specificity reached 95%. Two-thirds of patients in the cohort were female, and the median age was 53 years (Clin Gastroenterol Hepatol. 2016 May 31. doi: 10.1016/j.cgh.2016.04.032).

Overall, 7,928 patients (1.7%) had duodenal villous atrophy indicative of disease, including 2% of North Indians, 1.8% of Jewish individuals, 1.8% of other Americans, 1.5% of Middle Easterners, 1.1% of Hispanics, and 0.15% of East Asians, said the investigators. Thus, Jewish persons and Middle Eastern persons had a prevalence of celiac disease similar to that of other Americans. Prevalence also was similar among Ashkenazi and Sephardic Jews. In contrast, none of the 177 South Indians in the study were diagnosed with celiac disease, and both East Asians and Hispanics were significantly less likely to be receive a diagnosis than other Americans, with odds ratios of 0.08 (95% confidence interval, 0.04-0.17) and 0.58 (0.52-0.64), respectively, and P values less than .0001.

Importantly, celiac disease was significantly more common among patients from the Punjab region of India (3.1%) than among other North Indians (1.5%; P = .02). Past studies of celiac disease in India reported similar prevalences of compatible human leukocyte antigen (HLA) haplotypes as in Western countries, without notable regional trends within India, the researchers noted. Substantial regional variations in wheat consumption in India are more likely to explain their findings and patterns of case reports in past studies, they added.

Because the registry lacked serology data, patients diagnosed with celiac disease could have actually had tropical sprue or sprue-like enteropathy due to olmesartan, the researchers acknowledged. “In particular, multiple studies have shown that tropical sprue is still the most common cause of malabsorption syndrome in India, whereas celiac disease is emerging as a more important cause of malabsorption than previously thought,” they said. “However, such cases of tropical sprue and sprue-like enteropathy due to olmesartan are far less common than celiac disease in the United States.” The study also did not account for patients whose celiac disease only was diagnosed by serology and clinical symptoms, and the algorithm probably assigned some individuals who were Hispanic to other ethnicities, because only 7% of the cohort was classified as Hispanic, compared with about 16% of Americans in the 2010 U.S. Census, they noted. But ethnic misclassification was unlikely to have differed by celiac disease status, they said.

The National Institutes of Health partially supported the work. The authors had no disclosures.

The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.

The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis. Humira itself is approved for 10 indications.

A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.

The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale,

A spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.

While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.

It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.

“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.

But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.

“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”

The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.

“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.

“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.

Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”

According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.

The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis. Humira itself is approved for 10 indications.

A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.

The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale,

A spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.

While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.

It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.

“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.

But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.

“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”

The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.

“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.

“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.

Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”

According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The Food and Drug Administration’s Arthritis Advisory Committee, together with an added complement of dermatologists and gastroenterologists, unanimously recommended during meetings on July 12 and 13 that the agency license a biosimilar Humira (adalimumab) that is made by Amgen and a biosimilar Enbrel (etanercept) that is made by Sandoz for many of the same indications held by the reference drugs.

The FDA advisory panel that endorsed biosimilar Humira recommended the agent’s approval in a 26-0 vote for: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis in patients at least 4 years old, plaque psoriasis, adult Crohn’s disease, and adult ulcerative colitis. Humira itself is approved for 10 indications.

A slightly different group of 20 advisory panel members (without any gastroenterologists) voted 20-0 in favor of the FDA granting biosimilar Enbrel all five of the indications now held by Enbrel: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and plaque psoriasis.

The biosimilar Humira and the biosimilar Enbrel are, respectively, the third and fourth candidate biosimilars to emerge from the FDA’s development program and receive advisory committee scrutiny and support. The first agent through the process, biosimilar filgrastim (Zarxio) received FDA approval in 2015 and is available in the United States. Although the second biosimilar through the process, the tumor necrosis factor inhibitor Inflectra that is biosimilar Remicade (infliximab), received FDA approval in April of this year, it has not yet become available for sale,

A spokeswoman for the company that will market it, Pfizer, said that the company expects to start U.S. sales of Inflectra before the end of 2016.

While the Arthritis Advisory Committee ended each of its daylong deliberations for each of the two candidate biosimilars with unanimous support, the panelists’ discussions among themselves and with FDA staffers reflected some uncertainty with the biosimilar concept, especially during the first day when they focused on biosimilar Humira. The major sticking point revolved around the regulatory pathway to approval first established by the Biologics Price Competition and Innovation Act of 2009 and subsequently refined by the FDA that allows a candidate biosimilar to establish its biosimilarity primarily though the results of analytical studies that establish that the candidate molecule is highly similar to the reference molecule. This approval scheme uses clinical trials in a confirmatory role to establish biosimilarity rather than as the linchpin of approval.

It also means that the FDA can grant clinical indications to the biosimilar drug based not on the results from clinical trials, but based entirely on what have already been demonstrated as safe and effective clinical applications for the reference drug. For example, the biosimilar Humira underwent testing in two clinical studies showing similar efficacy and safety as Humira in patients with rheumatoid arthritis and in patients with plaque psoriasis, but received endorsements based on extrapolations for an additional five indications. Biosimilar Enbrel was compared with Enbrel in patients with plaque psoriasis only and still received extrapolated indications for the additional four rheumatologic conditions.

“This is a new level of extrapolation, across indications,” noted Sarah E. Streett, MD, a gastroenterologist at Stanford (Calif.) University, one of several panelists who initially voiced uncertainty about the concept.

But FDA staffer Nikolay P. Nikolov, MD, who led the agency’s presentation, assured the panelists that the concept of extrapolation was at the heart of biosimilar development and regulatory assessment.

“We have confidence from the data that the two molecules [the reference drug and biosimilar drug] are so similar that we can rely on the safety and efficacy of the reference product. The premise of our approach to biosimilars is that this is not a new molecule that we know nothing about.”

The other uncertainty about biosimilar Humira and biosimilar Enbrel that raised concerns of many panelists were the prospects for nonmedical switching once these drugs reach the market. Nonmedical switching refers to when an insurance company or pharmacy benefit manager substitutes a biosimilar for a reference drug without approval from or even the knowledge of the prescribing physician or the patient. Many of the people who spoke during the public forum period on both days of hearings voiced their concerns about this prospect.

“Nonmedical switching is a major concern of clinicians and policy makers, and we need greater clarification from the FDA,” said committee chair Daniel H. Solomon, MD, a rheumatologist and professor of medicine at Harvard Medical School in Boston.

“I see a remarkable disconnect between the public’s concerns [about nonmedical switching] and the charge to the committee. These are essential issues that need a forum to be aired out,” said panelist Steven F. Solga, MD, chief of gastroenterology at St. Luke’s Hospital in Bethlehem, Pa.

Dr. Nikolov assured committee members that the FDA recognized this concern and was working on it. “We appreciate the disconnect between the charge and the concerns of the community. I assure you that the issues brought up will be part of our discussions so we can get this [biosimilar pathway] implemented the right way.”

According to the FDA’s regulations, a biosimilar designation does not allow for nonmedical switching, something that could only happen under a related but distinct designation known as interchangeability. During the committee meeting on July 13, a FDA staffer said that the agency is currently developing guidance for an “interchangeable” designation and plans to have it available before then end of 2016.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

Adults with irritable bowel syndrome (IBS) who underwent psychotherapy improved more than about 75% of controls, and the effect “remained significant and medium in magnitude” for at least 6-12 months, according to a meta-analysis of 41 randomized, controlled trials reported in the July issue of Clinical Gastroenterology and Hepatology.

The finding “is particularly noteworthy because of the typically recurrent, persistent nature of IBS symptoms,” said Kelsey Laird, a doctoral student of clinical psychology at Vanderbilt University in Nashville, Tenn., together with her associates there. “Future research is needed to compare the longevity of treatment effects for psychotherapy with pharmacologic therapies, such as antidepressants,” they added. “Although it is beyond the scope of this review, it is also important to consider the mechanisms by which psychotherapies improve GI symptoms and to determine the ‘active ingredients’ responsible for this effect.”

©MacXever/Thinkstock

Up to 16% of individuals in the United States have IBS, and treating it costs anywhere from $950 million to $1.35 billion per year, the researchers noted. Other meta-analyses found psychotherapy about as effective as antidepressants for treating IBS-related GI symptoms over the short term, but its long-term efficacy was unknown, they added. Therefore, they searched PubMed, PsycINFO, Science Direct, and ProQuest through Aug. 15, 2015, identifying randomized controlled trials of psychological therapy and active or nonactive comparators. Psychotherapy included not only traditional psychodynamic and cognitive-behavioral therapies, but also mind-body approaches, such as relaxation training, biofeedback, and yoga, “which can be conceptualized as mindful movement,” Ms. Laird and her associates said. Comparators included support groups, education, sham treatments for hypnosis or biofeedback, online discussion forums, enhanced medical care, treatment as usual, symptom monitoring, and being wait-listed for psychological treatment (Clin Gastroenterol Hepatol. 2016 Jan 21. doi: 10.1016/j.cgh.2015.11.020). The 41 trials included 2,290 patients, comprising 1,183 assigned to the psychological modalities and 1,107 assigned to the various comparators. Taken together, the psychological modalities were associated with greater improvements in GI symptoms immediately after treatment, as compared with the grouped comparators. The Cohen’s d value was 0.69 (95% confidence interval, 0.52-0.86; P less than .001), indicating a medium effect size, the researchers said. Moreover, Cohen’s d values were 0.76 and 0.73, respectively, at short-term follow-up (1-6 months) and long-term follow-up (6-12 months). “On average, individuals who received psychotherapy had a greater reduction in GI symptoms after treatment than 75% of individuals assigned to a control condition,” the researchers concluded.

Effect sizes were similar among cognitive, cognitive-behavioral, and relaxation and hypnosis interventions, and between interventions delivered online and in person, the investigators also reported. Furthermore, longer durations or sessions of psychotherapy did not appear to further improve symptoms.

Study limitations included substantial variability between trials, and the fact that none of the 41 trials could be seen as having a low risk of bias in every domain assessed, the investigators said. “This was partially a result of the difficulty in blinding participants in psychological trials,” they noted. “However, even after excluding this domain, only nine trials were rated as low risk of bias in all remaining domains. Future studies should follow the CONSORT guidelines for [randomized controlled trials], use [intention-to-treat] designs, use active control conditions to control for nonspecific treatment effects, and assess treatment credibility and expectancy.”

The authors reported no funding sources and had no disclosures.

SAN DIEGO – Tumor necrosis factor inhibitors improved the extraintestinal manifestations of inflammatory bowel disease (IBD) among more than half of affected patients, according to a national cohort study.

“The best response rates were for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis,” said Dr. Thomas Greuter of University Hospital in Zürich. Patients responded similarly whether they received oral infliximab or subcutaneous adalimumab or certolizumab, he noted.

IBD often is associated with debilitating disorders of the skin, joints, eyes, and hepatobiliary tract, but “due to the lack of randomized, controlled trials, the therapy of extraintestinal manifestations remains rather empirical,” Dr. Greuter said at the annual Digestive Disease Week.

To study the role of anti-TNF agents in treating these disorders, he and his associates analyzed data for 1,249 patients from the national Swiss IBD Cohort Study between 2006 and 2010. Patients were typically in their mid-30s and had lived with IBD for about 9 years, he said.

A total of 366 patients (29%) had at least one extraintestinal manifestation of IBD – most commonly peripheral arthritis (75%), followed by aphthous stomatitis (24%), and ankylosing spondylitis (22%). In all, 213 (58%) patients received at least one anti-TNF agent, and 40% received the prescription specifically for extraintestinal manifestations. Nearly two-thirds of the patients received infliximab, while 22% received adalimumab and 15% received certolizumab.

About 55% of patients improved on anti-TNF therapy over an average of 7 years of follow-up, Dr. Greuter and his associates reported. Among all three anti-TNF agents, response rates ranged from 100% for psoriasis, to 80% for erythema nodosum and stomatitis, to 73% for arthritis and uveitis, to 50% for pyoderma granulosum. Overall rates of improvement were slightly higher for infliximab than for the other two drugs, but “adalimumab and certolizumab were used mostly as a second or a third-line anti-TNF agent, and the response rate to a second or third-line treatment was lower than for the first one,” Dr. Greuter said. Some patients also received corticosteroids and immunomodulators, but excluding this subgroup had little effect on rates of response to anti-TNF therapy, he added.

Dr. Greuter also reported that 11 patients (about 5% of the cohort) developed 14 new extraintestinal manifestations after starting anti-TNF agents – usually peripheral arthritis, but also pyoderma granulosum, aphthous stomatitis, psoriasis, and uveitis. “We cannot say if this was primary, or a side effect of treatment,” he said. These disorders usually improved if patients stayed on their anti-TNF agent, he added.

About two-thirds of patients in the cohort were female, more than three-quarters had Crohn’s disease, 19% had ulcerative colitis, and 3% had indeterminate colitis, he noted.

A research grant from the Swiss National Science Foundation funded the study. Dr. Greuter had no disclosures.

SAN DIEGO – Tumor necrosis factor inhibitors improved the extraintestinal manifestations of inflammatory bowel disease (IBD) among more than half of affected patients, according to a national cohort study.

“The best response rates were for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis,” said Dr. Thomas Greuter of University Hospital in Zürich. Patients responded similarly whether they received oral infliximab or subcutaneous adalimumab or certolizumab, he noted.

IBD often is associated with debilitating disorders of the skin, joints, eyes, and hepatobiliary tract, but “due to the lack of randomized, controlled trials, the therapy of extraintestinal manifestations remains rather empirical,” Dr. Greuter said at the annual Digestive Disease Week.

To study the role of anti-TNF agents in treating these disorders, he and his associates analyzed data for 1,249 patients from the national Swiss IBD Cohort Study between 2006 and 2010. Patients were typically in their mid-30s and had lived with IBD for about 9 years, he said.

A total of 366 patients (29%) had at least one extraintestinal manifestation of IBD – most commonly peripheral arthritis (75%), followed by aphthous stomatitis (24%), and ankylosing spondylitis (22%). In all, 213 (58%) patients received at least one anti-TNF agent, and 40% received the prescription specifically for extraintestinal manifestations. Nearly two-thirds of the patients received infliximab, while 22% received adalimumab and 15% received certolizumab.

About 55% of patients improved on anti-TNF therapy over an average of 7 years of follow-up, Dr. Greuter and his associates reported. Among all three anti-TNF agents, response rates ranged from 100% for psoriasis, to 80% for erythema nodosum and stomatitis, to 73% for arthritis and uveitis, to 50% for pyoderma granulosum. Overall rates of improvement were slightly higher for infliximab than for the other two drugs, but “adalimumab and certolizumab were used mostly as a second or a third-line anti-TNF agent, and the response rate to a second or third-line treatment was lower than for the first one,” Dr. Greuter said. Some patients also received corticosteroids and immunomodulators, but excluding this subgroup had little effect on rates of response to anti-TNF therapy, he added.

Dr. Greuter also reported that 11 patients (about 5% of the cohort) developed 14 new extraintestinal manifestations after starting anti-TNF agents – usually peripheral arthritis, but also pyoderma granulosum, aphthous stomatitis, psoriasis, and uveitis. “We cannot say if this was primary, or a side effect of treatment,” he said. These disorders usually improved if patients stayed on their anti-TNF agent, he added.

About two-thirds of patients in the cohort were female, more than three-quarters had Crohn’s disease, 19% had ulcerative colitis, and 3% had indeterminate colitis, he noted.

A research grant from the Swiss National Science Foundation funded the study. Dr. Greuter had no disclosures.

SAN DIEGO – Tumor necrosis factor inhibitors improved the extraintestinal manifestations of inflammatory bowel disease (IBD) among more than half of affected patients, according to a national cohort study.

“The best response rates were for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis,” said Dr. Thomas Greuter of University Hospital in Zürich. Patients responded similarly whether they received oral infliximab or subcutaneous adalimumab or certolizumab, he noted.

IBD often is associated with debilitating disorders of the skin, joints, eyes, and hepatobiliary tract, but “due to the lack of randomized, controlled trials, the therapy of extraintestinal manifestations remains rather empirical,” Dr. Greuter said at the annual Digestive Disease Week.

To study the role of anti-TNF agents in treating these disorders, he and his associates analyzed data for 1,249 patients from the national Swiss IBD Cohort Study between 2006 and 2010. Patients were typically in their mid-30s and had lived with IBD for about 9 years, he said.

A total of 366 patients (29%) had at least one extraintestinal manifestation of IBD – most commonly peripheral arthritis (75%), followed by aphthous stomatitis (24%), and ankylosing spondylitis (22%). In all, 213 (58%) patients received at least one anti-TNF agent, and 40% received the prescription specifically for extraintestinal manifestations. Nearly two-thirds of the patients received infliximab, while 22% received adalimumab and 15% received certolizumab.

About 55% of patients improved on anti-TNF therapy over an average of 7 years of follow-up, Dr. Greuter and his associates reported. Among all three anti-TNF agents, response rates ranged from 100% for psoriasis, to 80% for erythema nodosum and stomatitis, to 73% for arthritis and uveitis, to 50% for pyoderma granulosum. Overall rates of improvement were slightly higher for infliximab than for the other two drugs, but “adalimumab and certolizumab were used mostly as a second or a third-line anti-TNF agent, and the response rate to a second or third-line treatment was lower than for the first one,” Dr. Greuter said. Some patients also received corticosteroids and immunomodulators, but excluding this subgroup had little effect on rates of response to anti-TNF therapy, he added.

Dr. Greuter also reported that 11 patients (about 5% of the cohort) developed 14 new extraintestinal manifestations after starting anti-TNF agents – usually peripheral arthritis, but also pyoderma granulosum, aphthous stomatitis, psoriasis, and uveitis. “We cannot say if this was primary, or a side effect of treatment,” he said. These disorders usually improved if patients stayed on their anti-TNF agent, he added.

About two-thirds of patients in the cohort were female, more than three-quarters had Crohn’s disease, 19% had ulcerative colitis, and 3% had indeterminate colitis, he noted.

A research grant from the Swiss National Science Foundation funded the study. Dr. Greuter had no disclosures.