IBD & Intestinal Disorders

Treatment of relapsing or recurrent Clostridium difficile infection with frozen, orally administered capsules containing a solution of fecal matter from healthy unrelated donors had promising results, with diarrhea resolving in 90% of patients after one or two rounds of treatment.

“We demonstrated the feasibility of oral administration of frozen encapsulated fecal material from unrelated donors to treat patients with recurrent [Clostridium difficile infection (CDI)],” concluded Dr. Ilan Youngster, of the division of infectious diseases at Massachusetts General Hospital, Boston, and his associates. While the study was limited by the small number patients (20) and the lack of a placebo or comparator group, “if reproduced in future studies with active controls, these results may help make FMT accessible to a wider population of patients, in addition to potentially making the procedure safer.”

Courtesy CDC/Dr. Gilda Jones

The study was published Oct. 11 in JAMA, in conjunction with its presenation at ID Week 2014 (doi:10.1001/jama.2014.13875)

Instead of the most common type of fecal microbiota transplantation (FMT) procedures, which use a suspension of fresh stool from donors related to the patient to reconstitute the normal flora, this feasibility study evaluated the safety and effectiveness of FMT with fecal matter from unrelated, carefully screened healthy donors, which was processed into a solution that was placed into small capsules and then frozen.

The study enrolled 20 patients whose mean age was 64.5 years (one patient was aged 11, the rest were aged 17-89) between August 2013 and June 2014 at Massachusetts General. Patient had had at least three episodes of mild to moderate CDI and failed treatment with vancomycin, with or without an alternative antibiotic; or had been hospitalized with at least 2 episodes of severe CDI.

After one round of treatment with 15 capsules over 2 days, diarrhea resolved (defined as fewer than three bowel movements over 24 hours) in 14 of the 20 patients (70%); at 8 weeks, they remained symptom free. The remaining 6 patients were treated again, a mean of 7 days after the first treatment, and diarrhea resolved in 5. One of the 5 patients relapsed within the 8 week follow-up period, so the overall rate of diarrhea resolution at 8 weeks was 90%.

Overall health score before treatment was the only factor significantly associated with treatment response. Those who required a second treatment had more symptoms and had lower health scores before treatment than those who responded to the first treatment.

The number of daily bowel movements dropped from a median of five per day before treatment to a median of 2 at day 3, and one at 8 weeks, both statistically significant reductions from baseline. Patients also felt better, reflected in improvements in scores on health questionnaires evaluating overall and gastrointestinal health.

There were no cases of vomiting or aspiration and no serious adverse events were observed, Dr. Youngster said. Six patients experienced abdominal cramping and bloating after treatment, which were considered to be treatment related, but resolved.

The 90% clinical resolution rate with this treatment are comparable those in case studies and a randomized study using fresh stool preparations to treat CDI, Dr. Youngster said. “Larger studied are needed to confirm these results and to evaluate long-term safety and effectiveness.

The study was funded with internal hospital division funds. One author is a recipient of a research award sponsored by Seres Health, Cambridge, Mass., for an unrelated clinical trial of a C. difficile colitis treatment. No other author disclosures were reported.

emechcatie@frontlinemedcom.com

Treatment of relapsing or recurrent Clostridium difficile infection with frozen, orally administered capsules containing a solution of fecal matter from healthy unrelated donors had promising results, with diarrhea resolving in 90% of patients after one or two rounds of treatment.

“We demonstrated the feasibility of oral administration of frozen encapsulated fecal material from unrelated donors to treat patients with recurrent [Clostridium difficile infection (CDI)],” concluded Dr. Ilan Youngster, of the division of infectious diseases at Massachusetts General Hospital, Boston, and his associates. While the study was limited by the small number patients (20) and the lack of a placebo or comparator group, “if reproduced in future studies with active controls, these results may help make FMT accessible to a wider population of patients, in addition to potentially making the procedure safer.”

Courtesy CDC/Dr. Gilda Jones

The study was published Oct. 11 in JAMA, in conjunction with its presenation at ID Week 2014 (doi:10.1001/jama.2014.13875)

Instead of the most common type of fecal microbiota transplantation (FMT) procedures, which use a suspension of fresh stool from donors related to the patient to reconstitute the normal flora, this feasibility study evaluated the safety and effectiveness of FMT with fecal matter from unrelated, carefully screened healthy donors, which was processed into a solution that was placed into small capsules and then frozen.

The study enrolled 20 patients whose mean age was 64.5 years (one patient was aged 11, the rest were aged 17-89) between August 2013 and June 2014 at Massachusetts General. Patient had had at least three episodes of mild to moderate CDI and failed treatment with vancomycin, with or without an alternative antibiotic; or had been hospitalized with at least 2 episodes of severe CDI.

After one round of treatment with 15 capsules over 2 days, diarrhea resolved (defined as fewer than three bowel movements over 24 hours) in 14 of the 20 patients (70%); at 8 weeks, they remained symptom free. The remaining 6 patients were treated again, a mean of 7 days after the first treatment, and diarrhea resolved in 5. One of the 5 patients relapsed within the 8 week follow-up period, so the overall rate of diarrhea resolution at 8 weeks was 90%.

Overall health score before treatment was the only factor significantly associated with treatment response. Those who required a second treatment had more symptoms and had lower health scores before treatment than those who responded to the first treatment.

The number of daily bowel movements dropped from a median of five per day before treatment to a median of 2 at day 3, and one at 8 weeks, both statistically significant reductions from baseline. Patients also felt better, reflected in improvements in scores on health questionnaires evaluating overall and gastrointestinal health.

There were no cases of vomiting or aspiration and no serious adverse events were observed, Dr. Youngster said. Six patients experienced abdominal cramping and bloating after treatment, which were considered to be treatment related, but resolved.

The 90% clinical resolution rate with this treatment are comparable those in case studies and a randomized study using fresh stool preparations to treat CDI, Dr. Youngster said. “Larger studied are needed to confirm these results and to evaluate long-term safety and effectiveness.

The study was funded with internal hospital division funds. One author is a recipient of a research award sponsored by Seres Health, Cambridge, Mass., for an unrelated clinical trial of a C. difficile colitis treatment. No other author disclosures were reported.

emechcatie@frontlinemedcom.com

Treatment of relapsing or recurrent Clostridium difficile infection with frozen, orally administered capsules containing a solution of fecal matter from healthy unrelated donors had promising results, with diarrhea resolving in 90% of patients after one or two rounds of treatment.

“We demonstrated the feasibility of oral administration of frozen encapsulated fecal material from unrelated donors to treat patients with recurrent [Clostridium difficile infection (CDI)],” concluded Dr. Ilan Youngster, of the division of infectious diseases at Massachusetts General Hospital, Boston, and his associates. While the study was limited by the small number patients (20) and the lack of a placebo or comparator group, “if reproduced in future studies with active controls, these results may help make FMT accessible to a wider population of patients, in addition to potentially making the procedure safer.”

Courtesy CDC/Dr. Gilda Jones

The study was published Oct. 11 in JAMA, in conjunction with its presenation at ID Week 2014 (doi:10.1001/jama.2014.13875)

Instead of the most common type of fecal microbiota transplantation (FMT) procedures, which use a suspension of fresh stool from donors related to the patient to reconstitute the normal flora, this feasibility study evaluated the safety and effectiveness of FMT with fecal matter from unrelated, carefully screened healthy donors, which was processed into a solution that was placed into small capsules and then frozen.

The study enrolled 20 patients whose mean age was 64.5 years (one patient was aged 11, the rest were aged 17-89) between August 2013 and June 2014 at Massachusetts General. Patient had had at least three episodes of mild to moderate CDI and failed treatment with vancomycin, with or without an alternative antibiotic; or had been hospitalized with at least 2 episodes of severe CDI.

After one round of treatment with 15 capsules over 2 days, diarrhea resolved (defined as fewer than three bowel movements over 24 hours) in 14 of the 20 patients (70%); at 8 weeks, they remained symptom free. The remaining 6 patients were treated again, a mean of 7 days after the first treatment, and diarrhea resolved in 5. One of the 5 patients relapsed within the 8 week follow-up period, so the overall rate of diarrhea resolution at 8 weeks was 90%.

Overall health score before treatment was the only factor significantly associated with treatment response. Those who required a second treatment had more symptoms and had lower health scores before treatment than those who responded to the first treatment.

The number of daily bowel movements dropped from a median of five per day before treatment to a median of 2 at day 3, and one at 8 weeks, both statistically significant reductions from baseline. Patients also felt better, reflected in improvements in scores on health questionnaires evaluating overall and gastrointestinal health.

There were no cases of vomiting or aspiration and no serious adverse events were observed, Dr. Youngster said. Six patients experienced abdominal cramping and bloating after treatment, which were considered to be treatment related, but resolved.

The 90% clinical resolution rate with this treatment are comparable those in case studies and a randomized study using fresh stool preparations to treat CDI, Dr. Youngster said. “Larger studied are needed to confirm these results and to evaluate long-term safety and effectiveness.

The study was funded with internal hospital division funds. One author is a recipient of a research award sponsored by Seres Health, Cambridge, Mass., for an unrelated clinical trial of a C. difficile colitis treatment. No other author disclosures were reported.

emechcatie@frontlinemedcom.com

Contaminated duodenoscopes triggered a 2013 outbreak of a rare strain of Escherichia coli infections at a single hospital in northeastern Illinois, according to a report published online Oct. 7 in JAMA.

Unlike previous clusters of bacterial transmission related to these devices, this one could not be attributed to lapses in infection-control practices, defects in the duodenoscopes, or device malfunction. Instead, the carbapenem-resistant bacteria in this outbreak — NDM-producing (New Delhi metallo-beta-lactamase) E. coli — were recovered from the enclosed elevator channel of side-viewing duodenoscopes that had been cleaned, maintained, and used according to manufacturer’s instructions. “It appears that these devices have the potential to remain contaminated with pathogenic bacteria even after the recommended reprocessing is performed,” said Dr. Lauren Epstein of the division of healthcare quality promotion, Centers for Disease Control and Prevention, and her associates.

“Facilities should be aware of the potential for transmission of antimicrobial-resistant organisms via this route and should conduct regular reviews of their duodenoscope reprocessing procedures to ensure optimal manual cleaning and disinfection,” they noted.

The outbreak was discovered by a laboratory that routinely screens carbapenem-resistant Enterobacteriaceae isolates for NDM production and notifies the CDC of positive results, to ensure quick control of these dangerous organisms. The first case was identified from results of a urine culture, and six more patients who had been treated at the same hospital during a 4-month period also were found to have positive clinical cultures. Screening cultures were then performed on these patients’ roommates and on ward mates of the index case, turning up another two cases of carbapenem-resistant NDM-producing E. coli infection.

A review of the medical records showed that six of these patients had undergone endoscopic retrograde cholangiopancreatography (ERCP) at this hospital. The facility then notified all 226 patients who had undergone a procedure with any of the hospital’s three duodenoscopes during the preceding 9 months of their potential exposure, and offered them testing and treatment. A total of 27 additional cases were found, plus 1 additional case in the roommate of a patient who had been transferred to a long-term care facility.

In all, 35 of the 39 cases in this outbreak had been exposed to the hospital’s duodenoscopes.

A case-control analysis involving nine case patients and 27 control subjects who had been hospitalized during the study period showed that the infection was indeed strongly related to ERCP. Environmental cultures were collected from numerous areas of the hospital, and the only positive results were obtained from the elevator channels of two duodenoscopes. But no breaches were found in the reprocessing of the equipment.

Nevertheless, the hospital switched from automated high-level disinfection of the devices using an enzymatic cleaner to gas sterilization using ethylene oxide. Subsequent culturing showed no further contamination of the equipment, and no further cases of infection have occurred, the investigators said (JAMA 2014 [doi:10.1001/jama.2014.12720]).

Endoscopic facilities typically use high-level disinfection, as opposed to sterilization, for duodenoscopes. Although the switch to sterilization at this hospital may have been instrumental in containing the outbreak, the evidence from this single incident is not compelling enough to recommend that all such facilities make this change. Moreover, sterilization’s long processing and aeration time, the toxicity of some sterilizing agents to staff and patients, and its incompatibility with some devices make widespread adoption unlikely, Dr. Epstein and her associates said.

Unlike other endoscopes, duodenoscopes have an elevator channel “that allows for the use and manipulation of a guide wire. At the terminal end of the elevator channel is a mechanical piece containing a cantilevered elevator mechanism; the intricate design surrounding the elevator mechanism makes accessing all surfaces during manual cleaning difficult,” they noted.

Contaminated duodenoscopes triggered a 2013 outbreak of a rare strain of Escherichia coli infections at a single hospital in northeastern Illinois, according to a report published online Oct. 7 in JAMA.

Unlike previous clusters of bacterial transmission related to these devices, this one could not be attributed to lapses in infection-control practices, defects in the duodenoscopes, or device malfunction. Instead, the carbapenem-resistant bacteria in this outbreak — NDM-producing (New Delhi metallo-beta-lactamase) E. coli — were recovered from the enclosed elevator channel of side-viewing duodenoscopes that had been cleaned, maintained, and used according to manufacturer’s instructions. “It appears that these devices have the potential to remain contaminated with pathogenic bacteria even after the recommended reprocessing is performed,” said Dr. Lauren Epstein of the division of healthcare quality promotion, Centers for Disease Control and Prevention, and her associates.

“Facilities should be aware of the potential for transmission of antimicrobial-resistant organisms via this route and should conduct regular reviews of their duodenoscope reprocessing procedures to ensure optimal manual cleaning and disinfection,” they noted.

The outbreak was discovered by a laboratory that routinely screens carbapenem-resistant Enterobacteriaceae isolates for NDM production and notifies the CDC of positive results, to ensure quick control of these dangerous organisms. The first case was identified from results of a urine culture, and six more patients who had been treated at the same hospital during a 4-month period also were found to have positive clinical cultures. Screening cultures were then performed on these patients’ roommates and on ward mates of the index case, turning up another two cases of carbapenem-resistant NDM-producing E. coli infection.

A review of the medical records showed that six of these patients had undergone endoscopic retrograde cholangiopancreatography (ERCP) at this hospital. The facility then notified all 226 patients who had undergone a procedure with any of the hospital’s three duodenoscopes during the preceding 9 months of their potential exposure, and offered them testing and treatment. A total of 27 additional cases were found, plus 1 additional case in the roommate of a patient who had been transferred to a long-term care facility.

In all, 35 of the 39 cases in this outbreak had been exposed to the hospital’s duodenoscopes.

A case-control analysis involving nine case patients and 27 control subjects who had been hospitalized during the study period showed that the infection was indeed strongly related to ERCP. Environmental cultures were collected from numerous areas of the hospital, and the only positive results were obtained from the elevator channels of two duodenoscopes. But no breaches were found in the reprocessing of the equipment.

Nevertheless, the hospital switched from automated high-level disinfection of the devices using an enzymatic cleaner to gas sterilization using ethylene oxide. Subsequent culturing showed no further contamination of the equipment, and no further cases of infection have occurred, the investigators said (JAMA 2014 [doi:10.1001/jama.2014.12720]).

Endoscopic facilities typically use high-level disinfection, as opposed to sterilization, for duodenoscopes. Although the switch to sterilization at this hospital may have been instrumental in containing the outbreak, the evidence from this single incident is not compelling enough to recommend that all such facilities make this change. Moreover, sterilization’s long processing and aeration time, the toxicity of some sterilizing agents to staff and patients, and its incompatibility with some devices make widespread adoption unlikely, Dr. Epstein and her associates said.

Unlike other endoscopes, duodenoscopes have an elevator channel “that allows for the use and manipulation of a guide wire. At the terminal end of the elevator channel is a mechanical piece containing a cantilevered elevator mechanism; the intricate design surrounding the elevator mechanism makes accessing all surfaces during manual cleaning difficult,” they noted.

Contaminated duodenoscopes triggered a 2013 outbreak of a rare strain of Escherichia coli infections at a single hospital in northeastern Illinois, according to a report published online Oct. 7 in JAMA.

Unlike previous clusters of bacterial transmission related to these devices, this one could not be attributed to lapses in infection-control practices, defects in the duodenoscopes, or device malfunction. Instead, the carbapenem-resistant bacteria in this outbreak — NDM-producing (New Delhi metallo-beta-lactamase) E. coli — were recovered from the enclosed elevator channel of side-viewing duodenoscopes that had been cleaned, maintained, and used according to manufacturer’s instructions. “It appears that these devices have the potential to remain contaminated with pathogenic bacteria even after the recommended reprocessing is performed,” said Dr. Lauren Epstein of the division of healthcare quality promotion, Centers for Disease Control and Prevention, and her associates.

“Facilities should be aware of the potential for transmission of antimicrobial-resistant organisms via this route and should conduct regular reviews of their duodenoscope reprocessing procedures to ensure optimal manual cleaning and disinfection,” they noted.

The outbreak was discovered by a laboratory that routinely screens carbapenem-resistant Enterobacteriaceae isolates for NDM production and notifies the CDC of positive results, to ensure quick control of these dangerous organisms. The first case was identified from results of a urine culture, and six more patients who had been treated at the same hospital during a 4-month period also were found to have positive clinical cultures. Screening cultures were then performed on these patients’ roommates and on ward mates of the index case, turning up another two cases of carbapenem-resistant NDM-producing E. coli infection.

A review of the medical records showed that six of these patients had undergone endoscopic retrograde cholangiopancreatography (ERCP) at this hospital. The facility then notified all 226 patients who had undergone a procedure with any of the hospital’s three duodenoscopes during the preceding 9 months of their potential exposure, and offered them testing and treatment. A total of 27 additional cases were found, plus 1 additional case in the roommate of a patient who had been transferred to a long-term care facility.

In all, 35 of the 39 cases in this outbreak had been exposed to the hospital’s duodenoscopes.

A case-control analysis involving nine case patients and 27 control subjects who had been hospitalized during the study period showed that the infection was indeed strongly related to ERCP. Environmental cultures were collected from numerous areas of the hospital, and the only positive results were obtained from the elevator channels of two duodenoscopes. But no breaches were found in the reprocessing of the equipment.

Nevertheless, the hospital switched from automated high-level disinfection of the devices using an enzymatic cleaner to gas sterilization using ethylene oxide. Subsequent culturing showed no further contamination of the equipment, and no further cases of infection have occurred, the investigators said (JAMA 2014 [doi:10.1001/jama.2014.12720]).

Endoscopic facilities typically use high-level disinfection, as opposed to sterilization, for duodenoscopes. Although the switch to sterilization at this hospital may have been instrumental in containing the outbreak, the evidence from this single incident is not compelling enough to recommend that all such facilities make this change. Moreover, sterilization’s long processing and aeration time, the toxicity of some sterilizing agents to staff and patients, and its incompatibility with some devices make widespread adoption unlikely, Dr. Epstein and her associates said.

Unlike other endoscopes, duodenoscopes have an elevator channel “that allows for the use and manipulation of a guide wire. At the terminal end of the elevator channel is a mechanical piece containing a cantilevered elevator mechanism; the intricate design surrounding the elevator mechanism makes accessing all surfaces during manual cleaning difficult,” they noted.


The timing of introducing gluten into babies’ diets doesn’t alter their risk for developing celiac disease later, according to two separate reports published online Oct. 1 in the New England Journal of Medicine.

Currently, many clinicians recommend introducing small amounts of gluten during a proposed “window of opportunity” at 4-6 months of age – preferably while maintaining breast-feeding, which is considered protective – as a way of preventing the later development of celiac disease, especially in at-risk children. But this advice is based on the findings of a few small observational studies and remains controversial. To better examine whether the timing of gluten introduction influences the risk for celiac disease, separate groups of investigators performed prospective, randomized clinical trials assessing different dietary interventions in at-risk children.

© Renata Osinska/Thinkstock

They found that neither introducing small amounts of gluten at 4-6 months of age nor delaying that introduction until 12 months of age reduced the risk of later celiac disease, and that breastfeeding status also did not significantly affect that risk.

In the Risk of Celiac Disease and Age at Gluten Introduction (CELIPREV) trial, 707 newborns who had at least one affected first-degree relative were enrolled at 20 medical centers across Italy during a 5-year period. They were randomly assigned to gluten introduction (in the form of pasta, semolina, or biscuits) at age 6 months (379 babies) or delayed introduction at age 12 months (328 babies) and were followed for 5-11 years.

Overall, at age 10 years the prevalence of celiac disease autoimmunity was 16.5%, and the prevalence of overt celiac disease was 13.2%, said Dr. Elena Lionetti of the department of pediatrics at the University of Catania, Italy, and her associates.

At 2 years of age, the proportion of children with overt celiac disease was significantly higher in the group in which gluten was introduced at 6 months (12%) than in the delayed-introduction group (5%). However, that difference quickly resolved, so that by age 5 and persisting through age 10, the proportions of children with overt celiac disease were the same (16%) in both study groups. This pattern was the same for the proportions of children with celiac disease autoimmunity.

In addition, “We did not detect an effect of breastfeeding on the development of celiac disease: the mean duration of breastfeeding was very similar for at-risk children among whom celiac disease developed and at-risk children in whom the disorder did not develop (5.6 and 5.8 months, respectively),” the investigators said.

The only factor that was significantly associated with the development of both celiac autoimmunity and overt celiac disease was carrying a high-risk HLA genotype. The type of relative with celiac disease, the number of affected relatives, the child’s dietary pattern, and the presence or absence of early intestinal infection all showed no association.

“Our findings do not support the ‘window of tolerance’ hypothesis” and instead indicate that early dietary factors seem to play a minor role in celiac disease risk, Dr. Lionetti and her associates noted (N. Engl. J. Med. 2014 Oct. 2 [doi:10.1056/NEJMoa1400697]).

In the European multicenter project Prevent Coeliac Disease (PreventCD), 963 high-risk infants aged 0-3 months were enrolled through celiac disease organizations in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain. They were randomly assigned to receive either a small amount of wheat gluten (483 babies) or a matching placebo (480 babies) every day from 4 months through 6 months of age. The amount of gluten was equivalent to 2%-3% of that contained in a slice of bread.

At the conclusion of this intervention, parents were advised to introduce gluten gradually, in accordance with standardized recommendations. Parents also were allowed to breastfeed according to their own preferences, which permitted the researchers to assess several subgroups according to the duration and exclusivity of breastfeeding, said Dr. Sabine L. Vriezinga of the department of pediatrics at Leiden (the Netherlands) University Medical Center, and her associates.

The primary outcome of the trial – the frequency of celiac disease at age 3 years – was not significantly different between babies who received gluten (5.9%) and those who did not (4.5%). It also was no different among babies who were not breastfed, were breastfed for 3 or fewer months, were breastfed for 4-5 months, or were breastfed for 6 or more months. And it was not influenced by the country of origin; the number and type of affected relatives; the presence or absence of rotavirus vaccination; the presence or absence of early gastrointestinal or respiratory infections; or the mean dietary intake of gluten, the investigators said (N. Engl. J. Med. 2014 October 2 [doi:10.1056/NEJMoa1404172]).

These findings do not support guidelines that advocate early exposure to small amounts of gluten or maintenance of breastfeeding at the time of gluten introduction, “or any specific feeding recommendation with respect to the timing of gluten introduction for infants at risk for celiac disease,” Dr. Vriezinga and her associates said.

The PreventCD trial was supported by grants from the European Commission, the Azrieli Foundation, Deutsche Zöliakie Gesellschaft, Eurospital, Fondazione Celiachia, Fria Bröd, Instituto de Salud Carlos III, Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Komitet Badan Naukowych, Fundacja Nutricia, Hungarian Scientific Research Funds, Stichting Coeliakie Onderzoek Nederland, Thermo Fisher Scientific, and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. The CELIPREV trial was supported by the Celiac Foundation of the Italian Celiac Society. A few coauthors from Dr. Lionetti’s study were scientific consultants or received grant support from diagnostics companies, but most had no relevant financial disclosures. A few coauthors from Dr. Vriezinga’s study received speaker’s fees or research support from pharmaceutical companies, but the majority had no relevant financial disclosures.


The timing of introducing gluten into babies’ diets doesn’t alter their risk for developing celiac disease later, according to two separate reports published online Oct. 1 in the New England Journal of Medicine.

Currently, many clinicians recommend introducing small amounts of gluten during a proposed “window of opportunity” at 4-6 months of age – preferably while maintaining breast-feeding, which is considered protective – as a way of preventing the later development of celiac disease, especially in at-risk children. But this advice is based on the findings of a few small observational studies and remains controversial. To better examine whether the timing of gluten introduction influences the risk for celiac disease, separate groups of investigators performed prospective, randomized clinical trials assessing different dietary interventions in at-risk children.

© Renata Osinska/Thinkstock

They found that neither introducing small amounts of gluten at 4-6 months of age nor delaying that introduction until 12 months of age reduced the risk of later celiac disease, and that breastfeeding status also did not significantly affect that risk.

In the Risk of Celiac Disease and Age at Gluten Introduction (CELIPREV) trial, 707 newborns who had at least one affected first-degree relative were enrolled at 20 medical centers across Italy during a 5-year period. They were randomly assigned to gluten introduction (in the form of pasta, semolina, or biscuits) at age 6 months (379 babies) or delayed introduction at age 12 months (328 babies) and were followed for 5-11 years.

Overall, at age 10 years the prevalence of celiac disease autoimmunity was 16.5%, and the prevalence of overt celiac disease was 13.2%, said Dr. Elena Lionetti of the department of pediatrics at the University of Catania, Italy, and her associates.

At 2 years of age, the proportion of children with overt celiac disease was significantly higher in the group in which gluten was introduced at 6 months (12%) than in the delayed-introduction group (5%). However, that difference quickly resolved, so that by age 5 and persisting through age 10, the proportions of children with overt celiac disease were the same (16%) in both study groups. This pattern was the same for the proportions of children with celiac disease autoimmunity.

In addition, “We did not detect an effect of breastfeeding on the development of celiac disease: the mean duration of breastfeeding was very similar for at-risk children among whom celiac disease developed and at-risk children in whom the disorder did not develop (5.6 and 5.8 months, respectively),” the investigators said.

The only factor that was significantly associated with the development of both celiac autoimmunity and overt celiac disease was carrying a high-risk HLA genotype. The type of relative with celiac disease, the number of affected relatives, the child’s dietary pattern, and the presence or absence of early intestinal infection all showed no association.

“Our findings do not support the ‘window of tolerance’ hypothesis” and instead indicate that early dietary factors seem to play a minor role in celiac disease risk, Dr. Lionetti and her associates noted (N. Engl. J. Med. 2014 Oct. 2 [doi:10.1056/NEJMoa1400697]).

In the European multicenter project Prevent Coeliac Disease (PreventCD), 963 high-risk infants aged 0-3 months were enrolled through celiac disease organizations in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain. They were randomly assigned to receive either a small amount of wheat gluten (483 babies) or a matching placebo (480 babies) every day from 4 months through 6 months of age. The amount of gluten was equivalent to 2%-3% of that contained in a slice of bread.

At the conclusion of this intervention, parents were advised to introduce gluten gradually, in accordance with standardized recommendations. Parents also were allowed to breastfeed according to their own preferences, which permitted the researchers to assess several subgroups according to the duration and exclusivity of breastfeeding, said Dr. Sabine L. Vriezinga of the department of pediatrics at Leiden (the Netherlands) University Medical Center, and her associates.

The primary outcome of the trial – the frequency of celiac disease at age 3 years – was not significantly different between babies who received gluten (5.9%) and those who did not (4.5%). It also was no different among babies who were not breastfed, were breastfed for 3 or fewer months, were breastfed for 4-5 months, or were breastfed for 6 or more months. And it was not influenced by the country of origin; the number and type of affected relatives; the presence or absence of rotavirus vaccination; the presence or absence of early gastrointestinal or respiratory infections; or the mean dietary intake of gluten, the investigators said (N. Engl. J. Med. 2014 October 2 [doi:10.1056/NEJMoa1404172]).

These findings do not support guidelines that advocate early exposure to small amounts of gluten or maintenance of breastfeeding at the time of gluten introduction, “or any specific feeding recommendation with respect to the timing of gluten introduction for infants at risk for celiac disease,” Dr. Vriezinga and her associates said.

The PreventCD trial was supported by grants from the European Commission, the Azrieli Foundation, Deutsche Zöliakie Gesellschaft, Eurospital, Fondazione Celiachia, Fria Bröd, Instituto de Salud Carlos III, Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Komitet Badan Naukowych, Fundacja Nutricia, Hungarian Scientific Research Funds, Stichting Coeliakie Onderzoek Nederland, Thermo Fisher Scientific, and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. The CELIPREV trial was supported by the Celiac Foundation of the Italian Celiac Society. A few coauthors from Dr. Lionetti’s study were scientific consultants or received grant support from diagnostics companies, but most had no relevant financial disclosures. A few coauthors from Dr. Vriezinga’s study received speaker’s fees or research support from pharmaceutical companies, but the majority had no relevant financial disclosures.


The timing of introducing gluten into babies’ diets doesn’t alter their risk for developing celiac disease later, according to two separate reports published online Oct. 1 in the New England Journal of Medicine.

Currently, many clinicians recommend introducing small amounts of gluten during a proposed “window of opportunity” at 4-6 months of age – preferably while maintaining breast-feeding, which is considered protective – as a way of preventing the later development of celiac disease, especially in at-risk children. But this advice is based on the findings of a few small observational studies and remains controversial. To better examine whether the timing of gluten introduction influences the risk for celiac disease, separate groups of investigators performed prospective, randomized clinical trials assessing different dietary interventions in at-risk children.

© Renata Osinska/Thinkstock

They found that neither introducing small amounts of gluten at 4-6 months of age nor delaying that introduction until 12 months of age reduced the risk of later celiac disease, and that breastfeeding status also did not significantly affect that risk.

In the Risk of Celiac Disease and Age at Gluten Introduction (CELIPREV) trial, 707 newborns who had at least one affected first-degree relative were enrolled at 20 medical centers across Italy during a 5-year period. They were randomly assigned to gluten introduction (in the form of pasta, semolina, or biscuits) at age 6 months (379 babies) or delayed introduction at age 12 months (328 babies) and were followed for 5-11 years.

Overall, at age 10 years the prevalence of celiac disease autoimmunity was 16.5%, and the prevalence of overt celiac disease was 13.2%, said Dr. Elena Lionetti of the department of pediatrics at the University of Catania, Italy, and her associates.

At 2 years of age, the proportion of children with overt celiac disease was significantly higher in the group in which gluten was introduced at 6 months (12%) than in the delayed-introduction group (5%). However, that difference quickly resolved, so that by age 5 and persisting through age 10, the proportions of children with overt celiac disease were the same (16%) in both study groups. This pattern was the same for the proportions of children with celiac disease autoimmunity.

In addition, “We did not detect an effect of breastfeeding on the development of celiac disease: the mean duration of breastfeeding was very similar for at-risk children among whom celiac disease developed and at-risk children in whom the disorder did not develop (5.6 and 5.8 months, respectively),” the investigators said.

The only factor that was significantly associated with the development of both celiac autoimmunity and overt celiac disease was carrying a high-risk HLA genotype. The type of relative with celiac disease, the number of affected relatives, the child’s dietary pattern, and the presence or absence of early intestinal infection all showed no association.

“Our findings do not support the ‘window of tolerance’ hypothesis” and instead indicate that early dietary factors seem to play a minor role in celiac disease risk, Dr. Lionetti and her associates noted (N. Engl. J. Med. 2014 Oct. 2 [doi:10.1056/NEJMoa1400697]).

In the European multicenter project Prevent Coeliac Disease (PreventCD), 963 high-risk infants aged 0-3 months were enrolled through celiac disease organizations in Croatia, Germany, Hungary, Israel, Italy, the Netherlands, Poland, and Spain. They were randomly assigned to receive either a small amount of wheat gluten (483 babies) or a matching placebo (480 babies) every day from 4 months through 6 months of age. The amount of gluten was equivalent to 2%-3% of that contained in a slice of bread.

At the conclusion of this intervention, parents were advised to introduce gluten gradually, in accordance with standardized recommendations. Parents also were allowed to breastfeed according to their own preferences, which permitted the researchers to assess several subgroups according to the duration and exclusivity of breastfeeding, said Dr. Sabine L. Vriezinga of the department of pediatrics at Leiden (the Netherlands) University Medical Center, and her associates.

The primary outcome of the trial – the frequency of celiac disease at age 3 years – was not significantly different between babies who received gluten (5.9%) and those who did not (4.5%). It also was no different among babies who were not breastfed, were breastfed for 3 or fewer months, were breastfed for 4-5 months, or were breastfed for 6 or more months. And it was not influenced by the country of origin; the number and type of affected relatives; the presence or absence of rotavirus vaccination; the presence or absence of early gastrointestinal or respiratory infections; or the mean dietary intake of gluten, the investigators said (N. Engl. J. Med. 2014 October 2 [doi:10.1056/NEJMoa1404172]).

These findings do not support guidelines that advocate early exposure to small amounts of gluten or maintenance of breastfeeding at the time of gluten introduction, “or any specific feeding recommendation with respect to the timing of gluten introduction for infants at risk for celiac disease,” Dr. Vriezinga and her associates said.

The PreventCD trial was supported by grants from the European Commission, the Azrieli Foundation, Deutsche Zöliakie Gesellschaft, Eurospital, Fondazione Celiachia, Fria Bröd, Instituto de Salud Carlos III, Spanish Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Komitet Badan Naukowych, Fundacja Nutricia, Hungarian Scientific Research Funds, Stichting Coeliakie Onderzoek Nederland, Thermo Fisher Scientific, and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. The CELIPREV trial was supported by the Celiac Foundation of the Italian Celiac Society. A few coauthors from Dr. Lionetti’s study were scientific consultants or received grant support from diagnostics companies, but most had no relevant financial disclosures. A few coauthors from Dr. Vriezinga’s study received speaker’s fees or research support from pharmaceutical companies, but the majority had no relevant financial disclosures.

A risk stratification model that determined whether patients with Crohn’s disease needed computed tomography cut scans of these patients in emergency departments by 43%, with a miss rate of only 0.8%, researchers reported online in Clinical Gastroenterology and Hepatology.

Computed tomography scans yield nonsignificant findings for almost one-third of patients with Crohn’s disease (CD) who present to emergency departments, said Dr. Shail Govani of the University of Michigan in Ann Arbor and his associates. By using their model to identify patients with serious gastrointestinal complications as opposed to straightforward intestinal inflammation, emergency departments could prevent more than 250 cancer cases and save more than $80 million per decade in the United States, the investigators added.

Source: American Gastroenterological Association

Patients with CD may be exposed to increasing cumulative radiation levels, and 30% of this exposure occurs in emergency departments, with 75% due to CT scans, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.036]).

For the study, the investigators retrospectively reviewed electronic medical records from the University of Michigan from 2000 through 2011, identifying 613 adults with CD who made 1,095 visits that included CT scans within 24 hours of presentation. The researchers then modeled associations between laboratory values and perforation, abscess, or other serious complications as opposed to intestinal inflammation.

Patients averaged 1.8 CT scans during the decade-long study period, and the overall rate of CT scans during that time rose from 63% to 87%, the investigators said. Only 16.8% of scans revealed a complication that would change clinical management, they reported.

Only C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly associated with complications (odds ratio for CRP, 1.10; 95% confidence interval, 1.05-1.15; P less than .001; odds ratio for ESR, 1.02; 95% CI, 1.01-1.03; P less than .001), the researchers said. Adding ESR to 5 x CRP and not scanning patients with a resulting value of 10 or less would avoid CT scans in 18.5% of patients, they reported. But by using the more complex logistic regression model instead of the simpler equation, scans could be avoided for 43.0% of patients, with a miss rate of 0.8%, they said.

Based on the study, patients assessed as likely to have complications should undergo a standard CT scan of the abdomen and pelvis with nonbarium contrast to avoid barium peritonitis, said Dr. Govani and associates. Other patients should forego CT scans, have a consult with a gastroenterologist prior to further imaging, or undergo lower-radiation CT enterography, depending on presenting signs and probability of inflammation, they added.

The researchers said they were unable to construct good models that included obstruction as an outcome. Patients with suspected obstructions should have abdominal x-rays and then CT if an obstruction remained likely, they said.

"These models are limited in that they are retrospective and represent data from one center," the investigators added. "Although our internal validation with 10-fold cross-validation shows that these models have good performance characteristics, further external validation studies are needed to determine whether these models are generalizable to CD patients elsewhere."

The authors are prospectively testing the algorithms and hope to continue to validate and study them in emergency departments, they said.

The Inflammatory Bowel Disease Working Group, the Department of Veterans Affairs, and UCB supported the research. The authors reported having no conflicts of interest.

A risk stratification model that determined whether patients with Crohn’s disease needed computed tomography cut scans of these patients in emergency departments by 43%, with a miss rate of only 0.8%, researchers reported online in Clinical Gastroenterology and Hepatology.

Computed tomography scans yield nonsignificant findings for almost one-third of patients with Crohn’s disease (CD) who present to emergency departments, said Dr. Shail Govani of the University of Michigan in Ann Arbor and his associates. By using their model to identify patients with serious gastrointestinal complications as opposed to straightforward intestinal inflammation, emergency departments could prevent more than 250 cancer cases and save more than $80 million per decade in the United States, the investigators added.

Source: American Gastroenterological Association

Patients with CD may be exposed to increasing cumulative radiation levels, and 30% of this exposure occurs in emergency departments, with 75% due to CT scans, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.036]).

For the study, the investigators retrospectively reviewed electronic medical records from the University of Michigan from 2000 through 2011, identifying 613 adults with CD who made 1,095 visits that included CT scans within 24 hours of presentation. The researchers then modeled associations between laboratory values and perforation, abscess, or other serious complications as opposed to intestinal inflammation.

Patients averaged 1.8 CT scans during the decade-long study period, and the overall rate of CT scans during that time rose from 63% to 87%, the investigators said. Only 16.8% of scans revealed a complication that would change clinical management, they reported.

Only C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly associated with complications (odds ratio for CRP, 1.10; 95% confidence interval, 1.05-1.15; P less than .001; odds ratio for ESR, 1.02; 95% CI, 1.01-1.03; P less than .001), the researchers said. Adding ESR to 5 x CRP and not scanning patients with a resulting value of 10 or less would avoid CT scans in 18.5% of patients, they reported. But by using the more complex logistic regression model instead of the simpler equation, scans could be avoided for 43.0% of patients, with a miss rate of 0.8%, they said.

Based on the study, patients assessed as likely to have complications should undergo a standard CT scan of the abdomen and pelvis with nonbarium contrast to avoid barium peritonitis, said Dr. Govani and associates. Other patients should forego CT scans, have a consult with a gastroenterologist prior to further imaging, or undergo lower-radiation CT enterography, depending on presenting signs and probability of inflammation, they added.

The researchers said they were unable to construct good models that included obstruction as an outcome. Patients with suspected obstructions should have abdominal x-rays and then CT if an obstruction remained likely, they said.

"These models are limited in that they are retrospective and represent data from one center," the investigators added. "Although our internal validation with 10-fold cross-validation shows that these models have good performance characteristics, further external validation studies are needed to determine whether these models are generalizable to CD patients elsewhere."

The authors are prospectively testing the algorithms and hope to continue to validate and study them in emergency departments, they said.

The Inflammatory Bowel Disease Working Group, the Department of Veterans Affairs, and UCB supported the research. The authors reported having no conflicts of interest.

A risk stratification model that determined whether patients with Crohn’s disease needed computed tomography cut scans of these patients in emergency departments by 43%, with a miss rate of only 0.8%, researchers reported online in Clinical Gastroenterology and Hepatology.

Computed tomography scans yield nonsignificant findings for almost one-third of patients with Crohn’s disease (CD) who present to emergency departments, said Dr. Shail Govani of the University of Michigan in Ann Arbor and his associates. By using their model to identify patients with serious gastrointestinal complications as opposed to straightforward intestinal inflammation, emergency departments could prevent more than 250 cancer cases and save more than $80 million per decade in the United States, the investigators added.

Source: American Gastroenterological Association

Patients with CD may be exposed to increasing cumulative radiation levels, and 30% of this exposure occurs in emergency departments, with 75% due to CT scans, the researchers said (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.036]).

For the study, the investigators retrospectively reviewed electronic medical records from the University of Michigan from 2000 through 2011, identifying 613 adults with CD who made 1,095 visits that included CT scans within 24 hours of presentation. The researchers then modeled associations between laboratory values and perforation, abscess, or other serious complications as opposed to intestinal inflammation.

Patients averaged 1.8 CT scans during the decade-long study period, and the overall rate of CT scans during that time rose from 63% to 87%, the investigators said. Only 16.8% of scans revealed a complication that would change clinical management, they reported.

Only C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were significantly associated with complications (odds ratio for CRP, 1.10; 95% confidence interval, 1.05-1.15; P less than .001; odds ratio for ESR, 1.02; 95% CI, 1.01-1.03; P less than .001), the researchers said. Adding ESR to 5 x CRP and not scanning patients with a resulting value of 10 or less would avoid CT scans in 18.5% of patients, they reported. But by using the more complex logistic regression model instead of the simpler equation, scans could be avoided for 43.0% of patients, with a miss rate of 0.8%, they said.

Based on the study, patients assessed as likely to have complications should undergo a standard CT scan of the abdomen and pelvis with nonbarium contrast to avoid barium peritonitis, said Dr. Govani and associates. Other patients should forego CT scans, have a consult with a gastroenterologist prior to further imaging, or undergo lower-radiation CT enterography, depending on presenting signs and probability of inflammation, they added.

The researchers said they were unable to construct good models that included obstruction as an outcome. Patients with suspected obstructions should have abdominal x-rays and then CT if an obstruction remained likely, they said.

"These models are limited in that they are retrospective and represent data from one center," the investigators added. "Although our internal validation with 10-fold cross-validation shows that these models have good performance characteristics, further external validation studies are needed to determine whether these models are generalizable to CD patients elsewhere."

The authors are prospectively testing the algorithms and hope to continue to validate and study them in emergency departments, they said.

The Inflammatory Bowel Disease Working Group, the Department of Veterans Affairs, and UCB supported the research. The authors reported having no conflicts of interest.

Children receiving broad-spectrum antibiotics before age 2 years are at a slightly higher risk for obesity in early childhood, according to a recent study.

Children exposed to any antibiotics at least four times before turning 2 years old were 11% more likely to be obese between ages 2 and 5 years, even after accounting for other risk factors, compared with children receiving no antibiotics, reported Dr. L. Charles Bailey of Children’s Hospital of Philadelphia, and his associates.

But this association was driven primarily by broad-spectrum antibiotics, which increased the risk of obesity 16% in children who took them at least four times before 24 months old. No association with obesity was seen for narrow-spectrum antibiotics, which included penicillin and amoxicillin.

“If validated in other studies, this observation suggests a potentially modifiable risk factor for childhood obesity, given the relatively high use of broad-spectrum drugs, although interventions in this area have proven difficult in practice, Dr. Bailey’s team reported.

Dr. Bailey and his associates analyzed data from the medical records of 65,480 children who had at least three primary care visits between 2001 and 2009: one before 11 months old, one between 12 and 23 months, and one between 24 and 59 months as long as height and weight had been taken to calculate body mass index (BMI). The researchers defined obesity as 95th percentile or higher on the 2000 National Health and Nutrition Examination Survey growth norms.

Antibiotics were the most commonly prescribed medication to young children – provided an average 2.3 times each to 69% of the children before 24 months old – followed by oral steroids and antireflux medications.

Children exposed to just one round of broad-spectrum antibiotics between 0 and 5 months old had an 11% higher risk of obesity by age 5 years, compared with those receiving no antibiotics. Only 14% of children received antibiotics before 6 months old.

Children also were more likely to be obese if they had received steroids, were male, were Hispanic, had public insurance, went to an urban practice, or had been diagnosed with asthma or wheezing. But the researchers found no association between child obesity and antireflux medications or with pharyngitis, otitis media, or any other common infections.

The study was supported by the American Beverage Foundation for a Healthy America. The authors had no disclosures.

Children receiving broad-spectrum antibiotics before age 2 years are at a slightly higher risk for obesity in early childhood, according to a recent study.

Children exposed to any antibiotics at least four times before turning 2 years old were 11% more likely to be obese between ages 2 and 5 years, even after accounting for other risk factors, compared with children receiving no antibiotics, reported Dr. L. Charles Bailey of Children’s Hospital of Philadelphia, and his associates.

But this association was driven primarily by broad-spectrum antibiotics, which increased the risk of obesity 16% in children who took them at least four times before 24 months old. No association with obesity was seen for narrow-spectrum antibiotics, which included penicillin and amoxicillin.

“If validated in other studies, this observation suggests a potentially modifiable risk factor for childhood obesity, given the relatively high use of broad-spectrum drugs, although interventions in this area have proven difficult in practice, Dr. Bailey’s team reported.

Dr. Bailey and his associates analyzed data from the medical records of 65,480 children who had at least three primary care visits between 2001 and 2009: one before 11 months old, one between 12 and 23 months, and one between 24 and 59 months as long as height and weight had been taken to calculate body mass index (BMI). The researchers defined obesity as 95th percentile or higher on the 2000 National Health and Nutrition Examination Survey growth norms.

Antibiotics were the most commonly prescribed medication to young children – provided an average 2.3 times each to 69% of the children before 24 months old – followed by oral steroids and antireflux medications.

Children exposed to just one round of broad-spectrum antibiotics between 0 and 5 months old had an 11% higher risk of obesity by age 5 years, compared with those receiving no antibiotics. Only 14% of children received antibiotics before 6 months old.

Children also were more likely to be obese if they had received steroids, were male, were Hispanic, had public insurance, went to an urban practice, or had been diagnosed with asthma or wheezing. But the researchers found no association between child obesity and antireflux medications or with pharyngitis, otitis media, or any other common infections.

The study was supported by the American Beverage Foundation for a Healthy America. The authors had no disclosures.

Children receiving broad-spectrum antibiotics before age 2 years are at a slightly higher risk for obesity in early childhood, according to a recent study.

Children exposed to any antibiotics at least four times before turning 2 years old were 11% more likely to be obese between ages 2 and 5 years, even after accounting for other risk factors, compared with children receiving no antibiotics, reported Dr. L. Charles Bailey of Children’s Hospital of Philadelphia, and his associates.

But this association was driven primarily by broad-spectrum antibiotics, which increased the risk of obesity 16% in children who took them at least four times before 24 months old. No association with obesity was seen for narrow-spectrum antibiotics, which included penicillin and amoxicillin.

“If validated in other studies, this observation suggests a potentially modifiable risk factor for childhood obesity, given the relatively high use of broad-spectrum drugs, although interventions in this area have proven difficult in practice, Dr. Bailey’s team reported.

Dr. Bailey and his associates analyzed data from the medical records of 65,480 children who had at least three primary care visits between 2001 and 2009: one before 11 months old, one between 12 and 23 months, and one between 24 and 59 months as long as height and weight had been taken to calculate body mass index (BMI). The researchers defined obesity as 95th percentile or higher on the 2000 National Health and Nutrition Examination Survey growth norms.

Antibiotics were the most commonly prescribed medication to young children – provided an average 2.3 times each to 69% of the children before 24 months old – followed by oral steroids and antireflux medications.

Children exposed to just one round of broad-spectrum antibiotics between 0 and 5 months old had an 11% higher risk of obesity by age 5 years, compared with those receiving no antibiotics. Only 14% of children received antibiotics before 6 months old.

Children also were more likely to be obese if they had received steroids, were male, were Hispanic, had public insurance, went to an urban practice, or had been diagnosed with asthma or wheezing. But the researchers found no association between child obesity and antireflux medications or with pharyngitis, otitis media, or any other common infections.

The study was supported by the American Beverage Foundation for a Healthy America. The authors had no disclosures.

The tumor necrosis factor blocker adalimumab is now approved for treating children with Crohn’s disease, down to age 6 years, AbbVie, the manufacturer, announced on Sept. 25.

The approved indication is for “reducing signs and symptoms and inducing and maintaining clinical remission in patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.”

Approval of the pediatric indication was based on a phase III study of almost 200 patients aged 6-17 years with moderately to severely active disease, the IMAGINE-1 trial, the company said in the statement.

No new safety signals were seen in the study, according to the company.

As with other immunomodulators like adalimumab, the label includes a boxed warning about the increased risks of serious infections and malignancies associated with treatment, which are also explained in the adalimumab medication guide, distributed with each filled prescription.

Adalimumab is administered subcutaneously, with a maintenance dose administered every other week starting at 4 weeks, after induction doses are administered 2 weeks apart during the first month.

Adalimumab, marketed as Humira, was first approved in the United States in 2002. In Europe, it was approved for pediatric patients aged 6-17 years with severe active Crohn’s in 2012.

The updated prescribing information is available at http://www.rxabbvie.com/pdf/humira.pdf.

emechcatie@frontlinemedcom.com

The tumor necrosis factor blocker adalimumab is now approved for treating children with Crohn’s disease, down to age 6 years, AbbVie, the manufacturer, announced on Sept. 25.

The approved indication is for “reducing signs and symptoms and inducing and maintaining clinical remission in patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.”

Approval of the pediatric indication was based on a phase III study of almost 200 patients aged 6-17 years with moderately to severely active disease, the IMAGINE-1 trial, the company said in the statement.

No new safety signals were seen in the study, according to the company.

As with other immunomodulators like adalimumab, the label includes a boxed warning about the increased risks of serious infections and malignancies associated with treatment, which are also explained in the adalimumab medication guide, distributed with each filled prescription.

Adalimumab is administered subcutaneously, with a maintenance dose administered every other week starting at 4 weeks, after induction doses are administered 2 weeks apart during the first month.

Adalimumab, marketed as Humira, was first approved in the United States in 2002. In Europe, it was approved for pediatric patients aged 6-17 years with severe active Crohn’s in 2012.

The updated prescribing information is available at http://www.rxabbvie.com/pdf/humira.pdf.

emechcatie@frontlinemedcom.com

The tumor necrosis factor blocker adalimumab is now approved for treating children with Crohn’s disease, down to age 6 years, AbbVie, the manufacturer, announced on Sept. 25.

The approved indication is for “reducing signs and symptoms and inducing and maintaining clinical remission in patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.”

Approval of the pediatric indication was based on a phase III study of almost 200 patients aged 6-17 years with moderately to severely active disease, the IMAGINE-1 trial, the company said in the statement.

No new safety signals were seen in the study, according to the company.

As with other immunomodulators like adalimumab, the label includes a boxed warning about the increased risks of serious infections and malignancies associated with treatment, which are also explained in the adalimumab medication guide, distributed with each filled prescription.

Adalimumab is administered subcutaneously, with a maintenance dose administered every other week starting at 4 weeks, after induction doses are administered 2 weeks apart during the first month.

Adalimumab, marketed as Humira, was first approved in the United States in 2002. In Europe, it was approved for pediatric patients aged 6-17 years with severe active Crohn’s in 2012.

The updated prescribing information is available at http://www.rxabbvie.com/pdf/humira.pdf.

emechcatie@frontlinemedcom.com

Finding healthy stool donors for fecal transplant may be a tough prospect.

That’s what Australian researchers have discovered in the course of the FOCUS trial, which aims to determine whether fecal microbiota transplantation (FMT) is safe and efficacious in the treatment of chronic active ulcerative colitis and in the induction of remission.

Dr. Sudarshan Paramsothy and his colleagues at the University of New South Wales, Sydney, and the University of Melbourne, reported findings from donor recruitment for the FOCUS (Faecal Microbiota Transplantation in Ulcerative Colitis) trial at the American Gastroenterological Association’s 2014 James W. Freston Conference in Chicago.

The FOCUS study began enrolling patients in November, and is continuing to enroll, said Dr. Paramsothy. He and his colleagues also are continuing to recruit fecal donors. The data presented in Chicago were on an initial recruitment effort.

Overall, after screening, only 10% of recruits were considered eligible donors.

The researchers recruited donors through letters, newspaper ads, and online solicitations. They were told that they would be reimbursed for their time and for the transportation of their stool donations to the study site.

After responding, recruits were told that they would be expected to make stool donations five times a week for a minimum of 6 weeks.

The researchers had 116 potential donors over a 7-month recruitment period. Forty-seven declined immediately because of the 5-day-a-week donation requirement.

Twenty-seven had other issues, including medical comorbidities (13), risk factors for variant Cruetzfeldt-Jakob disease (6), and recent antibiotic use (1), that disqualified them from the study.

Thirty-eight potentially healthy donors underwent stool and blood testing. Fifteen of those donors were found to have a variety of parasites or indications of active infection that excluded them from donation: 5 had Dientamoeba fragilis, 5 had Blastocystis hominis, 1 had B. hominis and D. fragilis, 1 had Giardia intestinalis and D. fragilis, and 1 had norovirus and Clostridium difficile toxin, and 2 had leukocytes or erythrocytes on stool microscopy. One donor had indeterminate hepatitis C serology.

While it is not uncommon for people to have asymptomatic parasite carriage in the gastrointestinal tract, “we did not expect it in such a high proportion,” said Dr. Paramsothy. “Our screened donor population was not an at-risk group,” he said, adding that they were otherwise healthy and had no risk factors or gastrointestinal symptoms.

“Our detection rates may have been slightly higher as donor stool samples were sent to a pathology center with expert, specialized GI parasitologists for review,” Dr. Paramsothy said.

There’s also some question as to whether some parasites, such as Blastocystis and Dientamoeba, “are truly pathogenic or rather commensal organisms,” he said, adding that it was thought better to exclude patients with these parasites if there were any doubt.

That left 22 potential donors. Further questioning found that two had used antibiotics in between recruitment and stool testing, and one was living with a household member who was positive for D. fragilis.

Of the 19 remaining, 1 dropped out and 18 were screened again. Three were excluded because of a body mass index over 30 kg/m2, 1 because of illicit drug use, 1 because of irregular bowel movements after starting a new medication, and 1 because of uncontrolled anxiety and depression. Dr. Paramsothy said that high-BMI donors were excluded because some studies have shown that gut microbiota potentially influence insulin sensitivity and obesity. Illicit drug use is a red flag because it is potentially associated with blood-borne disease acquisition, he said.

At the end, there were only 12 healthy donors, 10% of the starting 116. Dr. Paramsothy said that it was not necessary to have a single donor for every single patient in the trial. He said he could not disclose currently the number needed for the study, however.

The donor results “suggest that while FMT is an exciting new therapy, it is difficult to identify appropriate and willing anonymous donors,” Dr. Paramsothy said. But that should not have an overall impact on FMT as a therapy, he said – rather, it might just make it harder for a small practice to establish an in-house FMT program.

Dr. Paramsothy reported no relevant financial conflicts.

aault@frontlinemedcom.com

Finding healthy stool donors for fecal transplant may be a tough prospect.

That’s what Australian researchers have discovered in the course of the FOCUS trial, which aims to determine whether fecal microbiota transplantation (FMT) is safe and efficacious in the treatment of chronic active ulcerative colitis and in the induction of remission.

Dr. Sudarshan Paramsothy and his colleagues at the University of New South Wales, Sydney, and the University of Melbourne, reported findings from donor recruitment for the FOCUS (Faecal Microbiota Transplantation in Ulcerative Colitis) trial at the American Gastroenterological Association’s 2014 James W. Freston Conference in Chicago.

The FOCUS study began enrolling patients in November, and is continuing to enroll, said Dr. Paramsothy. He and his colleagues also are continuing to recruit fecal donors. The data presented in Chicago were on an initial recruitment effort.

Overall, after screening, only 10% of recruits were considered eligible donors.

The researchers recruited donors through letters, newspaper ads, and online solicitations. They were told that they would be reimbursed for their time and for the transportation of their stool donations to the study site.

After responding, recruits were told that they would be expected to make stool donations five times a week for a minimum of 6 weeks.

The researchers had 116 potential donors over a 7-month recruitment period. Forty-seven declined immediately because of the 5-day-a-week donation requirement.

Twenty-seven had other issues, including medical comorbidities (13), risk factors for variant Cruetzfeldt-Jakob disease (6), and recent antibiotic use (1), that disqualified them from the study.

Thirty-eight potentially healthy donors underwent stool and blood testing. Fifteen of those donors were found to have a variety of parasites or indications of active infection that excluded them from donation: 5 had Dientamoeba fragilis, 5 had Blastocystis hominis, 1 had B. hominis and D. fragilis, 1 had Giardia intestinalis and D. fragilis, and 1 had norovirus and Clostridium difficile toxin, and 2 had leukocytes or erythrocytes on stool microscopy. One donor had indeterminate hepatitis C serology.

While it is not uncommon for people to have asymptomatic parasite carriage in the gastrointestinal tract, “we did not expect it in such a high proportion,” said Dr. Paramsothy. “Our screened donor population was not an at-risk group,” he said, adding that they were otherwise healthy and had no risk factors or gastrointestinal symptoms.

“Our detection rates may have been slightly higher as donor stool samples were sent to a pathology center with expert, specialized GI parasitologists for review,” Dr. Paramsothy said.

There’s also some question as to whether some parasites, such as Blastocystis and Dientamoeba, “are truly pathogenic or rather commensal organisms,” he said, adding that it was thought better to exclude patients with these parasites if there were any doubt.

That left 22 potential donors. Further questioning found that two had used antibiotics in between recruitment and stool testing, and one was living with a household member who was positive for D. fragilis.

Of the 19 remaining, 1 dropped out and 18 were screened again. Three were excluded because of a body mass index over 30 kg/m2, 1 because of illicit drug use, 1 because of irregular bowel movements after starting a new medication, and 1 because of uncontrolled anxiety and depression. Dr. Paramsothy said that high-BMI donors were excluded because some studies have shown that gut microbiota potentially influence insulin sensitivity and obesity. Illicit drug use is a red flag because it is potentially associated with blood-borne disease acquisition, he said.

At the end, there were only 12 healthy donors, 10% of the starting 116. Dr. Paramsothy said that it was not necessary to have a single donor for every single patient in the trial. He said he could not disclose currently the number needed for the study, however.

The donor results “suggest that while FMT is an exciting new therapy, it is difficult to identify appropriate and willing anonymous donors,” Dr. Paramsothy said. But that should not have an overall impact on FMT as a therapy, he said – rather, it might just make it harder for a small practice to establish an in-house FMT program.

Dr. Paramsothy reported no relevant financial conflicts.

aault@frontlinemedcom.com

Finding healthy stool donors for fecal transplant may be a tough prospect.

That’s what Australian researchers have discovered in the course of the FOCUS trial, which aims to determine whether fecal microbiota transplantation (FMT) is safe and efficacious in the treatment of chronic active ulcerative colitis and in the induction of remission.

Dr. Sudarshan Paramsothy and his colleagues at the University of New South Wales, Sydney, and the University of Melbourne, reported findings from donor recruitment for the FOCUS (Faecal Microbiota Transplantation in Ulcerative Colitis) trial at the American Gastroenterological Association’s 2014 James W. Freston Conference in Chicago.

The FOCUS study began enrolling patients in November, and is continuing to enroll, said Dr. Paramsothy. He and his colleagues also are continuing to recruit fecal donors. The data presented in Chicago were on an initial recruitment effort.

Overall, after screening, only 10% of recruits were considered eligible donors.

The researchers recruited donors through letters, newspaper ads, and online solicitations. They were told that they would be reimbursed for their time and for the transportation of their stool donations to the study site.

After responding, recruits were told that they would be expected to make stool donations five times a week for a minimum of 6 weeks.

The researchers had 116 potential donors over a 7-month recruitment period. Forty-seven declined immediately because of the 5-day-a-week donation requirement.

Twenty-seven had other issues, including medical comorbidities (13), risk factors for variant Cruetzfeldt-Jakob disease (6), and recent antibiotic use (1), that disqualified them from the study.

Thirty-eight potentially healthy donors underwent stool and blood testing. Fifteen of those donors were found to have a variety of parasites or indications of active infection that excluded them from donation: 5 had Dientamoeba fragilis, 5 had Blastocystis hominis, 1 had B. hominis and D. fragilis, 1 had Giardia intestinalis and D. fragilis, and 1 had norovirus and Clostridium difficile toxin, and 2 had leukocytes or erythrocytes on stool microscopy. One donor had indeterminate hepatitis C serology.

While it is not uncommon for people to have asymptomatic parasite carriage in the gastrointestinal tract, “we did not expect it in such a high proportion,” said Dr. Paramsothy. “Our screened donor population was not an at-risk group,” he said, adding that they were otherwise healthy and had no risk factors or gastrointestinal symptoms.

“Our detection rates may have been slightly higher as donor stool samples were sent to a pathology center with expert, specialized GI parasitologists for review,” Dr. Paramsothy said.

There’s also some question as to whether some parasites, such as Blastocystis and Dientamoeba, “are truly pathogenic or rather commensal organisms,” he said, adding that it was thought better to exclude patients with these parasites if there were any doubt.

That left 22 potential donors. Further questioning found that two had used antibiotics in between recruitment and stool testing, and one was living with a household member who was positive for D. fragilis.

Of the 19 remaining, 1 dropped out and 18 were screened again. Three were excluded because of a body mass index over 30 kg/m2, 1 because of illicit drug use, 1 because of irregular bowel movements after starting a new medication, and 1 because of uncontrolled anxiety and depression. Dr. Paramsothy said that high-BMI donors were excluded because some studies have shown that gut microbiota potentially influence insulin sensitivity and obesity. Illicit drug use is a red flag because it is potentially associated with blood-borne disease acquisition, he said.

At the end, there were only 12 healthy donors, 10% of the starting 116. Dr. Paramsothy said that it was not necessary to have a single donor for every single patient in the trial. He said he could not disclose currently the number needed for the study, however.

The donor results “suggest that while FMT is an exciting new therapy, it is difficult to identify appropriate and willing anonymous donors,” Dr. Paramsothy said. But that should not have an overall impact on FMT as a therapy, he said – rather, it might just make it harder for a small practice to establish an in-house FMT program.

Dr. Paramsothy reported no relevant financial conflicts.

aault@frontlinemedcom.com

WASHINGTON – A rationally designed microbiome-based pill successfully eradicated recurrent Clostridium difficile infection in 29 of 30 patients in an early study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Preliminary data were presented at the 2014 James W. Freston Conference sponsored by the American Gastroenterological Association in August.

CDC/D. Holdeman

The patients in the phase I/II study were divided into two separate 15-patient cohorts and were given two different dose levels of the therapy, SER-109. The drug contains spores from gram-positive bacteria that are taken from stool and then purified to kill the vegetative bacteria, said David Cook, Ph.D., executive vice president and chief scientific officer of Cambridge, Mass.–based Seres Health.

The therapy appears to work by restoring the gut flora to a normal balance after having been disrupted by antibiotic treatment.

It is not the first attempt to encapsulate a fecal transplant; Dr. Thomas Louie of the University of Calgary (Alberta), presented data on his very effective formulation against C. difficile at the ID Week annual meeting in 2013.

In the current study, the first cohort received a mean dose of 1.5 × 10⁹ spores and the second cohort received a dose of 1 × 10⁸ spores. In the early studies, the number of pills given to achieve that dose varied. The aim is to contain the dose in a few tablets for a commercial product, Dr. Cook said.

All doses were given on 1 or 2 days at the study’s start; there was no need for additional doses.

Patients were as young as 22 years old and as old as 88 years, and all had three or more laboratory-confirmed C. difficile infections over the previous year. They had to have a life expectancy of 3 months or longer and be able to give informed consent. They were excluded if they had any immunosuppression, a history of irritable bowel disease, total colectomy, cirrhosis, a need for antibiotics within 6 weeks of baseline, prior fecal transplant, or if they were in intensive care. There were 10 women and five men in each cohort.

After patients stopped taking antibiotics, there was a washout period after which they took SER-109. Stool was collected on day four and at 1, 2, 4, 8, and 24 weeks. Efficacy was assessed at the 8-week time point.

In the first group, 13 of the 15 patients achieved the protocol-defined endpoint: absence of C. difficile over the 8 weeks.

The two patients who failed had self-limited, transient diarrhea with a positive C. difficile test, but neither required antibiotics and both recovered within 24 hours, so they were considered to not have recurrent C. difficile, said Dr. Cook. In the second cohort, 14 of the 15 patients were free of C. difficile at 8 weeks. The patient who failed had diarrhea and a positive C. difficile test, and the diarrhea did not resolve on its own. She required antibiotics to achieve remission.

There were no serious adverse events in the study.

The company hopes to eventually conduct a phase III study and seek Food and Drug Administration approval, but it is too early to say when that might occur, said Dr. Cook.

aault@frontlinemedcom.com

On Twitter @aliciaault

This story was updated on October 14.

WASHINGTON – A rationally designed microbiome-based pill successfully eradicated recurrent Clostridium difficile infection in 29 of 30 patients in an early study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Preliminary data were presented at the 2014 James W. Freston Conference sponsored by the American Gastroenterological Association in August.

CDC/D. Holdeman

The patients in the phase I/II study were divided into two separate 15-patient cohorts and were given two different dose levels of the therapy, SER-109. The drug contains spores from gram-positive bacteria that are taken from stool and then purified to kill the vegetative bacteria, said David Cook, Ph.D., executive vice president and chief scientific officer of Cambridge, Mass.–based Seres Health.

The therapy appears to work by restoring the gut flora to a normal balance after having been disrupted by antibiotic treatment.

It is not the first attempt to encapsulate a fecal transplant; Dr. Thomas Louie of the University of Calgary (Alberta), presented data on his very effective formulation against C. difficile at the ID Week annual meeting in 2013.

In the current study, the first cohort received a mean dose of 1.5 × 10⁹ spores and the second cohort received a dose of 1 × 10⁸ spores. In the early studies, the number of pills given to achieve that dose varied. The aim is to contain the dose in a few tablets for a commercial product, Dr. Cook said.

All doses were given on 1 or 2 days at the study’s start; there was no need for additional doses.

Patients were as young as 22 years old and as old as 88 years, and all had three or more laboratory-confirmed C. difficile infections over the previous year. They had to have a life expectancy of 3 months or longer and be able to give informed consent. They were excluded if they had any immunosuppression, a history of irritable bowel disease, total colectomy, cirrhosis, a need for antibiotics within 6 weeks of baseline, prior fecal transplant, or if they were in intensive care. There were 10 women and five men in each cohort.

After patients stopped taking antibiotics, there was a washout period after which they took SER-109. Stool was collected on day four and at 1, 2, 4, 8, and 24 weeks. Efficacy was assessed at the 8-week time point.

In the first group, 13 of the 15 patients achieved the protocol-defined endpoint: absence of C. difficile over the 8 weeks.

The two patients who failed had self-limited, transient diarrhea with a positive C. difficile test, but neither required antibiotics and both recovered within 24 hours, so they were considered to not have recurrent C. difficile, said Dr. Cook. In the second cohort, 14 of the 15 patients were free of C. difficile at 8 weeks. The patient who failed had diarrhea and a positive C. difficile test, and the diarrhea did not resolve on its own. She required antibiotics to achieve remission.

There were no serious adverse events in the study.

The company hopes to eventually conduct a phase III study and seek Food and Drug Administration approval, but it is too early to say when that might occur, said Dr. Cook.

aault@frontlinemedcom.com

On Twitter @aliciaault

This story was updated on October 14.

WASHINGTON – A rationally designed microbiome-based pill successfully eradicated recurrent Clostridium difficile infection in 29 of 30 patients in an early study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Preliminary data were presented at the 2014 James W. Freston Conference sponsored by the American Gastroenterological Association in August.

CDC/D. Holdeman

The patients in the phase I/II study were divided into two separate 15-patient cohorts and were given two different dose levels of the therapy, SER-109. The drug contains spores from gram-positive bacteria that are taken from stool and then purified to kill the vegetative bacteria, said David Cook, Ph.D., executive vice president and chief scientific officer of Cambridge, Mass.–based Seres Health.

The therapy appears to work by restoring the gut flora to a normal balance after having been disrupted by antibiotic treatment.

It is not the first attempt to encapsulate a fecal transplant; Dr. Thomas Louie of the University of Calgary (Alberta), presented data on his very effective formulation against C. difficile at the ID Week annual meeting in 2013.

In the current study, the first cohort received a mean dose of 1.5 × 10⁹ spores and the second cohort received a dose of 1 × 10⁸ spores. In the early studies, the number of pills given to achieve that dose varied. The aim is to contain the dose in a few tablets for a commercial product, Dr. Cook said.

All doses were given on 1 or 2 days at the study’s start; there was no need for additional doses.

Patients were as young as 22 years old and as old as 88 years, and all had three or more laboratory-confirmed C. difficile infections over the previous year. They had to have a life expectancy of 3 months or longer and be able to give informed consent. They were excluded if they had any immunosuppression, a history of irritable bowel disease, total colectomy, cirrhosis, a need for antibiotics within 6 weeks of baseline, prior fecal transplant, or if they were in intensive care. There were 10 women and five men in each cohort.

After patients stopped taking antibiotics, there was a washout period after which they took SER-109. Stool was collected on day four and at 1, 2, 4, 8, and 24 weeks. Efficacy was assessed at the 8-week time point.

In the first group, 13 of the 15 patients achieved the protocol-defined endpoint: absence of C. difficile over the 8 weeks.

The two patients who failed had self-limited, transient diarrhea with a positive C. difficile test, but neither required antibiotics and both recovered within 24 hours, so they were considered to not have recurrent C. difficile, said Dr. Cook. In the second cohort, 14 of the 15 patients were free of C. difficile at 8 weeks. The patient who failed had diarrhea and a positive C. difficile test, and the diarrhea did not resolve on its own. She required antibiotics to achieve remission.

There were no serious adverse events in the study.

The company hopes to eventually conduct a phase III study and seek Food and Drug Administration approval, but it is too early to say when that might occur, said Dr. Cook.

aault@frontlinemedcom.com

On Twitter @aliciaault

This story was updated on October 14.

A gluten-free diet benefited asymptomatic patients with serologic markers for celiac disease in a prospective randomized study.

The findings support active screening for celiac disease in patients at risk for the disease, even if symptoms aren’t present, according to Dr. Kalle Kurppa of the University of Tampere (Finland) and Tampere University Hospital.

The report is in the September issue of Gastroenterology (doi.org/10.1053/j.gastro.2014.05.003).

After 1 year, 20 adults with endomysial antibodies (EmA) who were randomized to a gluten-free diet (GFD) experienced significant increases in mean mucosal villous height:crypt depth values, significantly decreased levels of celiac-associated antibodies, and greater improvement in gastrointestinal symptoms, compared with 20 patients randomized to a gluten-containing diet. For example, mean small bowel mucosal villous height:crypt depth increased from 1.0 to about 2.8 in the GFD group, and from 0.8 to about 0.9 in the gluten-containing diet group, and total Gastrointestinal Symptoms Rating Scale scores improved significantly (–0.4 difference in mean change from baseline, favoring a GFD), as did individual scores for diarrhea, indigestion, and reflux in the GFD group, wrote Dr. Kurppa and colleagues.

The patients in the GFD group also experienced reduced indigestion, reflux, and anxiety, and better health as measured by Psychological, General Health, and Well-Being scores and most Short Form–36 scores, they noted.

Only social function scores on the Short Form–36 improved more in the gluten-containing diet group (–8.3 difference in mean change from baseline, favoring a gluten-containing diet).

The subjects in both groups had a median age of 42 years, and the groups were similar with respect to sex, medical history, and associated conditions.

No differences were seen between the two groups with respect to laboratory test results, bone mineral density, or body composition, and the subjects in the GFD group did not report any negative effects or reactions to the diet. After trial completion, 92% reported adherence to the gluten-free diet, and 85% said they expected to remain on the diet, the investigators noted.

Because celiac disease affects 1%-2% of the population, but is difficult to detect because of clinical heterogeneity, wide-scale screening with noninvasive serologic testing is frequently suggested.

"However, the only current treatment of the condition, a lifelong strict gluten-free diet, is restrictive and difficult to maintain and thus the positive effects of the screening are not straightforward," the investigators noted, adding that results of prior studies exploring the benefits of a gluten-free diet have been inconsistent – particularly for asymptomatic patients.

Another problem is that wide-scale screening often detects asymptomatic seropositive subjects with only mild enteropathy or even normal small-bowel mucosa, and it is unclear whether these individuals actually suffer from a true gluten-induced clinical disease, they said.

"The results of this randomized study showed that screen-detected and even apparently asymptomatic EmA-positive patients benefit from a gluten-free diet as measured by extensive clinical, serologic, and histologic parameters," the investigators said.

The fact that subjects who considered themselves asymptomatic experienced improvement in the current study suggests that "the patients may in fact have accepted mild symptoms as normal and recognized them as abnormal only later when on the diet," they said.

The findings support active screening for celiac disease in patients at risk, but the potential consequences of screening – particularly on social functioning, should be considered on an individual basis, they said, adding that prospective studies are needed "to unravel whether screen-detected seropositive subjects with completely normal small-bowel mucosal histology should be treated."

This study was supported by the Academy of Finland Research Council for Health, the Competitive Research Funding of the Pirkanmaa Hospital District, the Sigrid Juselius Foundation, the Finnish Foundation for Research, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, and the Finnish Celiac Society. The authors reported having no disclosures.

A gluten-free diet benefited asymptomatic patients with serologic markers for celiac disease in a prospective randomized study.

The findings support active screening for celiac disease in patients at risk for the disease, even if symptoms aren’t present, according to Dr. Kalle Kurppa of the University of Tampere (Finland) and Tampere University Hospital.

The report is in the September issue of Gastroenterology (doi.org/10.1053/j.gastro.2014.05.003).

After 1 year, 20 adults with endomysial antibodies (EmA) who were randomized to a gluten-free diet (GFD) experienced significant increases in mean mucosal villous height:crypt depth values, significantly decreased levels of celiac-associated antibodies, and greater improvement in gastrointestinal symptoms, compared with 20 patients randomized to a gluten-containing diet. For example, mean small bowel mucosal villous height:crypt depth increased from 1.0 to about 2.8 in the GFD group, and from 0.8 to about 0.9 in the gluten-containing diet group, and total Gastrointestinal Symptoms Rating Scale scores improved significantly (–0.4 difference in mean change from baseline, favoring a GFD), as did individual scores for diarrhea, indigestion, and reflux in the GFD group, wrote Dr. Kurppa and colleagues.

The patients in the GFD group also experienced reduced indigestion, reflux, and anxiety, and better health as measured by Psychological, General Health, and Well-Being scores and most Short Form–36 scores, they noted.

Only social function scores on the Short Form–36 improved more in the gluten-containing diet group (–8.3 difference in mean change from baseline, favoring a gluten-containing diet).

The subjects in both groups had a median age of 42 years, and the groups were similar with respect to sex, medical history, and associated conditions.

No differences were seen between the two groups with respect to laboratory test results, bone mineral density, or body composition, and the subjects in the GFD group did not report any negative effects or reactions to the diet. After trial completion, 92% reported adherence to the gluten-free diet, and 85% said they expected to remain on the diet, the investigators noted.

Because celiac disease affects 1%-2% of the population, but is difficult to detect because of clinical heterogeneity, wide-scale screening with noninvasive serologic testing is frequently suggested.

"However, the only current treatment of the condition, a lifelong strict gluten-free diet, is restrictive and difficult to maintain and thus the positive effects of the screening are not straightforward," the investigators noted, adding that results of prior studies exploring the benefits of a gluten-free diet have been inconsistent – particularly for asymptomatic patients.

Another problem is that wide-scale screening often detects asymptomatic seropositive subjects with only mild enteropathy or even normal small-bowel mucosa, and it is unclear whether these individuals actually suffer from a true gluten-induced clinical disease, they said.

"The results of this randomized study showed that screen-detected and even apparently asymptomatic EmA-positive patients benefit from a gluten-free diet as measured by extensive clinical, serologic, and histologic parameters," the investigators said.

The fact that subjects who considered themselves asymptomatic experienced improvement in the current study suggests that "the patients may in fact have accepted mild symptoms as normal and recognized them as abnormal only later when on the diet," they said.

The findings support active screening for celiac disease in patients at risk, but the potential consequences of screening – particularly on social functioning, should be considered on an individual basis, they said, adding that prospective studies are needed "to unravel whether screen-detected seropositive subjects with completely normal small-bowel mucosal histology should be treated."

This study was supported by the Academy of Finland Research Council for Health, the Competitive Research Funding of the Pirkanmaa Hospital District, the Sigrid Juselius Foundation, the Finnish Foundation for Research, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, and the Finnish Celiac Society. The authors reported having no disclosures.

A gluten-free diet benefited asymptomatic patients with serologic markers for celiac disease in a prospective randomized study.

The findings support active screening for celiac disease in patients at risk for the disease, even if symptoms aren’t present, according to Dr. Kalle Kurppa of the University of Tampere (Finland) and Tampere University Hospital.

The report is in the September issue of Gastroenterology (doi.org/10.1053/j.gastro.2014.05.003).

After 1 year, 20 adults with endomysial antibodies (EmA) who were randomized to a gluten-free diet (GFD) experienced significant increases in mean mucosal villous height:crypt depth values, significantly decreased levels of celiac-associated antibodies, and greater improvement in gastrointestinal symptoms, compared with 20 patients randomized to a gluten-containing diet. For example, mean small bowel mucosal villous height:crypt depth increased from 1.0 to about 2.8 in the GFD group, and from 0.8 to about 0.9 in the gluten-containing diet group, and total Gastrointestinal Symptoms Rating Scale scores improved significantly (–0.4 difference in mean change from baseline, favoring a GFD), as did individual scores for diarrhea, indigestion, and reflux in the GFD group, wrote Dr. Kurppa and colleagues.

The patients in the GFD group also experienced reduced indigestion, reflux, and anxiety, and better health as measured by Psychological, General Health, and Well-Being scores and most Short Form–36 scores, they noted.

Only social function scores on the Short Form–36 improved more in the gluten-containing diet group (–8.3 difference in mean change from baseline, favoring a gluten-containing diet).

The subjects in both groups had a median age of 42 years, and the groups were similar with respect to sex, medical history, and associated conditions.

No differences were seen between the two groups with respect to laboratory test results, bone mineral density, or body composition, and the subjects in the GFD group did not report any negative effects or reactions to the diet. After trial completion, 92% reported adherence to the gluten-free diet, and 85% said they expected to remain on the diet, the investigators noted.

Because celiac disease affects 1%-2% of the population, but is difficult to detect because of clinical heterogeneity, wide-scale screening with noninvasive serologic testing is frequently suggested.

"However, the only current treatment of the condition, a lifelong strict gluten-free diet, is restrictive and difficult to maintain and thus the positive effects of the screening are not straightforward," the investigators noted, adding that results of prior studies exploring the benefits of a gluten-free diet have been inconsistent – particularly for asymptomatic patients.

Another problem is that wide-scale screening often detects asymptomatic seropositive subjects with only mild enteropathy or even normal small-bowel mucosa, and it is unclear whether these individuals actually suffer from a true gluten-induced clinical disease, they said.

"The results of this randomized study showed that screen-detected and even apparently asymptomatic EmA-positive patients benefit from a gluten-free diet as measured by extensive clinical, serologic, and histologic parameters," the investigators said.

The fact that subjects who considered themselves asymptomatic experienced improvement in the current study suggests that "the patients may in fact have accepted mild symptoms as normal and recognized them as abnormal only later when on the diet," they said.

The findings support active screening for celiac disease in patients at risk, but the potential consequences of screening – particularly on social functioning, should be considered on an individual basis, they said, adding that prospective studies are needed "to unravel whether screen-detected seropositive subjects with completely normal small-bowel mucosal histology should be treated."

This study was supported by the Academy of Finland Research Council for Health, the Competitive Research Funding of the Pirkanmaa Hospital District, the Sigrid Juselius Foundation, the Finnish Foundation for Research, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, and the Finnish Celiac Society. The authors reported having no disclosures.