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Anti-TNF Exposure Influences Efficacy of Subsequent Therapies in UC
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
, based on results of a large meta-analysis.
Patients previously treated with TNF antagonists were less likely to respond to lymphocyte trafficking inhibitors but more likely to achieve remission on Janus kinase (JAK) inhibitors, Han Hee Lee, MD, PhD, of the University of California San Diego, and colleagues reported.
“Treatment options for patients with moderate-severe ulcerative colitis have increased in the last decade with the availability of six different classes of medications,” investigators wrote in Clinical Gastroenterology and Hepatology (2024 Dec. doi:10.1016/j.cgh.2024.12.007). “There is wide interindividual variability in response to specific medications, and drivers of this heterogeneity are critical to understand to be able to choose the best therapy for each individual patient.”
To learn more about the impacts of anti-TNF exposure on subsequent advanced therapies, the investigators conducted a systematic review and meta-analysis of 17 phase 2 and 3 trials. The dataset included 8,871 adults with moderate-severe UC.
The primary outcome was induction of clinical remission at 6–14 weeks, most often defined as a Mayo Clinic score of 2 or lower with no subscore greater than 1. Endoscopic improvement, generally defined as a Mayo endoscopic subscore of 0 or 1, was evaluated as a secondary endpoint.
Advanced therapies were grouped by mechanism of action, including lymphocyte trafficking inhibitors, JAK inhibitors, and interleukin (IL)-12/23 and IL-23 antagonists. Odds ratios for treatment versus placebo were calculated separately for each subgroup, and a ratio of odds ratios was then used to assess whether prior TNF exposure modified drug effect. Analyses were conducted on an intention-to-treat basis, restricted to approved dosing when multiple regimens were tested.
Across five trials of lymphocyte trafficking inhibitors including 2,046 patients, efficacy was significantly greater in TNF-naïve patients compared with those who had prior TNF exposure. The odds of achieving clinical remission were nearly doubled in the TNF-naïve group (ratio of odds ratios [ROR], 1.88; 95% CI, 1.02–3.49).
In six trials of JAK inhibitors including 3,015 patients, remission rates were higher among TNF-exposed patients com-pared with TNF-naïve patients (ROR, 0.47; 95% CI, 0.22–1.01).
In six trials of IL-12/23 and IL-23 antagonists, including 3,810 patients, prior TNF exposure did not significantly modify treatment outcomes (ROR, 1.07; 95% CI, 0.64–1.80). Within individual trials, ustekinumab showed a trend toward great-er efficacy in TNF-exposed patients, whereas selective IL-23 antagonists performed similarly regardless of TNF exposure history.
Secondary analyses of endoscopic improvement yielded results consistent with the primary endpoint. Statistical heterogeneity across trials was minimal, and all included studies were rated at low risk of bias.
The investigators noted several limitations. For example, therapies were grouped broadly by mechanism of action, although specific biologic effects could potentially differ within groups. The analysis also could not account for patients who had failed two or more classes of advanced therapy, which may independently reduce the likelihood of response.
Still, Lee and colleagues suggested that the findings deserve a closer look.
“[T]here is significant heterogeneity of treatment efficacy for induction of remission with different advanced therapies in patients with moderate-severe UC based on prior exposure to TNF antagonists,” they concluded. “Future studies on the mechanistic insight for these intriguing observations are warranted.”
The study was supported by the Leona and Harry B. Helmsley Trust, the National Institutes of Health, and the Centers for Disease Control and Prevention. The investigators disclosed relationships with AbbVie, Ferring, Pfizer, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Formula Type May Fuel NEC in Premature Infants
DENVER – , according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.
Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.
The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.
Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.
Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.
Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis.
Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.
The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.
Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.
Younger Babies at Greater Risk
Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.
“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.
“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.
The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.
Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.
However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.
Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.
The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
DENVER – , according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.
Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.
The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.
Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.
Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.
Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis.
Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.
The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.
Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.
Younger Babies at Greater Risk
Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.
“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.
“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.
The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.
Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.
However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.
Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.
The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
DENVER – , according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.
Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.
The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.
Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.
Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.
Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis.
Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.
The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.
Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.
Younger Babies at Greater Risk
Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.
“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.
“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.
The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.
Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.
However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.
Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.
The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Fecal Transplant Benefits in Primary C Difficile Infection Similar to Vancomycin
, with efficacy that is comparable to the standard treatment of vancomycin, and in some measures, showing even stronger efficacy, new research showed.
“FMT, prepared and administered according to international guidelines, is an effective and safe treatment option for C difficile infections, which should be considered for all patients with the infection,” first author Frederik Emil Juul, MD, PhD, of the Clinical Effectiveness Research Group, University of Oslo, in Oslo, Norway, told GI & Hepatology News.
FMT even showed a numerical superiority to vancomycin, which, though not statistically significant, “indicates that FMT has the potential to change the current practice of antibiotic therapy and may establish FMT as a first-line treatment for primary CDI,” the authors further asserted in the study, published recently in the Annals of Internal Medicine.
In the treatment of antibiotic-associated colitis due to CDI, vancomycin or fidaxomicin are the standard therapies, yet up to 20% of patients experience one or more symptom recurrences following successful initial antibiotic treatment, prompting the need for continued antibiotic regimens, resulting in increased costs and potential adverse events, while contributing to antibiotic resistance.
FMT, designed to restore a normal functional colonic microenvironment with the transfer of a healthy person’s stool, though still somewhat controversial, has gained acceptance and favor in recent years in the treatment of recurrent CDI, however, research has been lacking on its efficacy in the treatment of primary CDI.
With a previous proof-of-concept trial and observational study showing promising results in primary CDI, Juul and colleagues conducted the current randomized, open-label noninferiority trial.
For the multi-center study, 100 adult patients with CDI, defined as C diff toxin in stool and at least three loose stools daily, and no previous CDI within 1 year prior to enrollment, were randomized at 20 hospitals in Norway to receive either FMT, administered as an enema, without antibiotic pretreatment, or oral vancomycin at a dose of 125 mg, four times daily for 10 days.
The patients had a median age of about 70 years; more than 40% of patients had a Charlson Comorbidity Index score of ≥ 4, indicating severe comorbidity, and a third had severe CDI.
With the trial showing favorable results, a data and safety monitoring board recommended stopping the trial for efficacy and noninferiority after about half of the planned enrollment was reached.
The primary endpoint of a clinical cure, defined as firm stools or less than three bowel movements daily and no disease recurrence within 60 days without additional treatment, was observed in 34 of 51 patients who received FMT (66.7%) compared with 30 of 49 of those receiving vancomycin (61.2%; difference, 5.4 percentage points; P for noninferiority < .001).
The results contradict the theory that response to FMT is 25 percentage points lower than response to vancomycin, the authors noted.
The proportion of patients with clinical cure at day 14 was 70.6% in the FMT group and 77.6% in the vancomycin group, and among those patients, two (5.6%) in the FMT group had disease recurrence compared with eight (21.1%) in the vancomycin group between days 15 and 60.
In the FMT group, 11 patients received additional treatment compared with four in the vancomycin group, predominantly oral vancomycin in both groups.
Despite the high rates of severe comorbidity among the patients at baseline, a subgroup analyses showed no significant differences in treatment effects based on factors including sex, age group, Charlson Comorbidity Index score, or CDI severity.
Importantly, there were also no significant differences in adverse events between the groups.
“Our results indicate that it is reasonable to treat patients with primary CDI with FMT and provide antibiotics only to patients with ongoing symptoms or recurrence after FMT,” the authors concluded.
FMT Faces Challenges in the US
FMT specifically consists of direct instillation of fecal matter to the upper gastrointestinal tract, via capsules or duodenal infusion, or the lower gastrointestinal tract via colonoscopy or enema.
While an AGA guideline issued in 2024 endorsed FMT for the prevention of recurrent, refractory, or fulminant CDI in select adults not responding to standard antibiotics, the association underscored important caveats, including a low quality of evidence, and concluded that FMT could not yet be recommended for other gastrointestinal conditions.
The treatment meanwhile has faced an uphill battle in the US. The provision of screened FMT inocula through the nonprofit OpenBiome, previously the country’s largest stool bank, was recently suspended amid FDA policy changes.
And while other commercial-grade biotherapeutic products Rebyota and Vowst, have received FDA approval, cost and insurance coverage can be significant barriers, said Elizabeth Hohmann, MD, of the Infectious Disease Division at Massachusetts General Hospital, Boston, in an editorial published with the study.
“Currently approved options are expensive and are not available to many who might benefit for various reasons, primarily cost,” she said.
Acceptance Higher in Europe
In Europe, and particularly Norway, acceptance of FMT for CDI and other indications has been more favorable, and while regulation of the treatment has varied among European countries, a new regulation to be implemented by the European Union in 2027 will improve standardization of the production, handling, storage, and other factors of FMT, Juul told GI & Hepatology News.
“I believe the new regulations will make the treatment more available to patients, and a standardization of the FMT production will make future trials more comparable and useful across countries,” he said.
Juul said he further expects that “our results will lower the threshold for choosing FMT as treatment in primary infections. I know that Denmark also gives FMT to patients with primary CDI.”
Quality of Life
Hohmann, who has treated many patients with recurrent CDI with FMT, noted that a key factor that should be underscored is how much better patients can feel after the treatment.
“Although there are no quality of life surveys in [the current study], had they been done, I suspect quality of life might have been higher in the FMT group; in my experience, people feel better after microbiome restoration.”
She added that her patients “report feeling much better, and that’s why I keep doing it,” she said. “I’ve had an 80-year-old patient tell me he’s going back to snow shoveling; another saying she can return to yoga classes.”
“When you have had bad gut microbiome dysbiosis that becomes normal, you feel a lot better,” Hohmann said.
In the treatment of primary CDI, however, Hohmann said the prospects, at least in the US, are likely slim.
“I do not believe that we in the United States will see FMT as a primary treatment of C difficile infection anytime soon,” she wrote in the editorial.
Nevertheless, Hohmann asserted that “FMT should remain available, with appropriate sources of carefully screened inocula for care and for further research into the many illnesses and therapies that are influenced by the health of the gut microbiome.”
This study received funding from the South-East Norway Health Trust. Hohmann had no disclosures to report.
A version of this article appeared on Medscape.com.
, with efficacy that is comparable to the standard treatment of vancomycin, and in some measures, showing even stronger efficacy, new research showed.
“FMT, prepared and administered according to international guidelines, is an effective and safe treatment option for C difficile infections, which should be considered for all patients with the infection,” first author Frederik Emil Juul, MD, PhD, of the Clinical Effectiveness Research Group, University of Oslo, in Oslo, Norway, told GI & Hepatology News.
FMT even showed a numerical superiority to vancomycin, which, though not statistically significant, “indicates that FMT has the potential to change the current practice of antibiotic therapy and may establish FMT as a first-line treatment for primary CDI,” the authors further asserted in the study, published recently in the Annals of Internal Medicine.
In the treatment of antibiotic-associated colitis due to CDI, vancomycin or fidaxomicin are the standard therapies, yet up to 20% of patients experience one or more symptom recurrences following successful initial antibiotic treatment, prompting the need for continued antibiotic regimens, resulting in increased costs and potential adverse events, while contributing to antibiotic resistance.
FMT, designed to restore a normal functional colonic microenvironment with the transfer of a healthy person’s stool, though still somewhat controversial, has gained acceptance and favor in recent years in the treatment of recurrent CDI, however, research has been lacking on its efficacy in the treatment of primary CDI.
With a previous proof-of-concept trial and observational study showing promising results in primary CDI, Juul and colleagues conducted the current randomized, open-label noninferiority trial.
For the multi-center study, 100 adult patients with CDI, defined as C diff toxin in stool and at least three loose stools daily, and no previous CDI within 1 year prior to enrollment, were randomized at 20 hospitals in Norway to receive either FMT, administered as an enema, without antibiotic pretreatment, or oral vancomycin at a dose of 125 mg, four times daily for 10 days.
The patients had a median age of about 70 years; more than 40% of patients had a Charlson Comorbidity Index score of ≥ 4, indicating severe comorbidity, and a third had severe CDI.
With the trial showing favorable results, a data and safety monitoring board recommended stopping the trial for efficacy and noninferiority after about half of the planned enrollment was reached.
The primary endpoint of a clinical cure, defined as firm stools or less than three bowel movements daily and no disease recurrence within 60 days without additional treatment, was observed in 34 of 51 patients who received FMT (66.7%) compared with 30 of 49 of those receiving vancomycin (61.2%; difference, 5.4 percentage points; P for noninferiority < .001).
The results contradict the theory that response to FMT is 25 percentage points lower than response to vancomycin, the authors noted.
The proportion of patients with clinical cure at day 14 was 70.6% in the FMT group and 77.6% in the vancomycin group, and among those patients, two (5.6%) in the FMT group had disease recurrence compared with eight (21.1%) in the vancomycin group between days 15 and 60.
In the FMT group, 11 patients received additional treatment compared with four in the vancomycin group, predominantly oral vancomycin in both groups.
Despite the high rates of severe comorbidity among the patients at baseline, a subgroup analyses showed no significant differences in treatment effects based on factors including sex, age group, Charlson Comorbidity Index score, or CDI severity.
Importantly, there were also no significant differences in adverse events between the groups.
“Our results indicate that it is reasonable to treat patients with primary CDI with FMT and provide antibiotics only to patients with ongoing symptoms or recurrence after FMT,” the authors concluded.
FMT Faces Challenges in the US
FMT specifically consists of direct instillation of fecal matter to the upper gastrointestinal tract, via capsules or duodenal infusion, or the lower gastrointestinal tract via colonoscopy or enema.
While an AGA guideline issued in 2024 endorsed FMT for the prevention of recurrent, refractory, or fulminant CDI in select adults not responding to standard antibiotics, the association underscored important caveats, including a low quality of evidence, and concluded that FMT could not yet be recommended for other gastrointestinal conditions.
The treatment meanwhile has faced an uphill battle in the US. The provision of screened FMT inocula through the nonprofit OpenBiome, previously the country’s largest stool bank, was recently suspended amid FDA policy changes.
And while other commercial-grade biotherapeutic products Rebyota and Vowst, have received FDA approval, cost and insurance coverage can be significant barriers, said Elizabeth Hohmann, MD, of the Infectious Disease Division at Massachusetts General Hospital, Boston, in an editorial published with the study.
“Currently approved options are expensive and are not available to many who might benefit for various reasons, primarily cost,” she said.
Acceptance Higher in Europe
In Europe, and particularly Norway, acceptance of FMT for CDI and other indications has been more favorable, and while regulation of the treatment has varied among European countries, a new regulation to be implemented by the European Union in 2027 will improve standardization of the production, handling, storage, and other factors of FMT, Juul told GI & Hepatology News.
“I believe the new regulations will make the treatment more available to patients, and a standardization of the FMT production will make future trials more comparable and useful across countries,” he said.
Juul said he further expects that “our results will lower the threshold for choosing FMT as treatment in primary infections. I know that Denmark also gives FMT to patients with primary CDI.”
Quality of Life
Hohmann, who has treated many patients with recurrent CDI with FMT, noted that a key factor that should be underscored is how much better patients can feel after the treatment.
“Although there are no quality of life surveys in [the current study], had they been done, I suspect quality of life might have been higher in the FMT group; in my experience, people feel better after microbiome restoration.”
She added that her patients “report feeling much better, and that’s why I keep doing it,” she said. “I’ve had an 80-year-old patient tell me he’s going back to snow shoveling; another saying she can return to yoga classes.”
“When you have had bad gut microbiome dysbiosis that becomes normal, you feel a lot better,” Hohmann said.
In the treatment of primary CDI, however, Hohmann said the prospects, at least in the US, are likely slim.
“I do not believe that we in the United States will see FMT as a primary treatment of C difficile infection anytime soon,” she wrote in the editorial.
Nevertheless, Hohmann asserted that “FMT should remain available, with appropriate sources of carefully screened inocula for care and for further research into the many illnesses and therapies that are influenced by the health of the gut microbiome.”
This study received funding from the South-East Norway Health Trust. Hohmann had no disclosures to report.
A version of this article appeared on Medscape.com.
, with efficacy that is comparable to the standard treatment of vancomycin, and in some measures, showing even stronger efficacy, new research showed.
“FMT, prepared and administered according to international guidelines, is an effective and safe treatment option for C difficile infections, which should be considered for all patients with the infection,” first author Frederik Emil Juul, MD, PhD, of the Clinical Effectiveness Research Group, University of Oslo, in Oslo, Norway, told GI & Hepatology News.
FMT even showed a numerical superiority to vancomycin, which, though not statistically significant, “indicates that FMT has the potential to change the current practice of antibiotic therapy and may establish FMT as a first-line treatment for primary CDI,” the authors further asserted in the study, published recently in the Annals of Internal Medicine.
In the treatment of antibiotic-associated colitis due to CDI, vancomycin or fidaxomicin are the standard therapies, yet up to 20% of patients experience one or more symptom recurrences following successful initial antibiotic treatment, prompting the need for continued antibiotic regimens, resulting in increased costs and potential adverse events, while contributing to antibiotic resistance.
FMT, designed to restore a normal functional colonic microenvironment with the transfer of a healthy person’s stool, though still somewhat controversial, has gained acceptance and favor in recent years in the treatment of recurrent CDI, however, research has been lacking on its efficacy in the treatment of primary CDI.
With a previous proof-of-concept trial and observational study showing promising results in primary CDI, Juul and colleagues conducted the current randomized, open-label noninferiority trial.
For the multi-center study, 100 adult patients with CDI, defined as C diff toxin in stool and at least three loose stools daily, and no previous CDI within 1 year prior to enrollment, were randomized at 20 hospitals in Norway to receive either FMT, administered as an enema, without antibiotic pretreatment, or oral vancomycin at a dose of 125 mg, four times daily for 10 days.
The patients had a median age of about 70 years; more than 40% of patients had a Charlson Comorbidity Index score of ≥ 4, indicating severe comorbidity, and a third had severe CDI.
With the trial showing favorable results, a data and safety monitoring board recommended stopping the trial for efficacy and noninferiority after about half of the planned enrollment was reached.
The primary endpoint of a clinical cure, defined as firm stools or less than three bowel movements daily and no disease recurrence within 60 days without additional treatment, was observed in 34 of 51 patients who received FMT (66.7%) compared with 30 of 49 of those receiving vancomycin (61.2%; difference, 5.4 percentage points; P for noninferiority < .001).
The results contradict the theory that response to FMT is 25 percentage points lower than response to vancomycin, the authors noted.
The proportion of patients with clinical cure at day 14 was 70.6% in the FMT group and 77.6% in the vancomycin group, and among those patients, two (5.6%) in the FMT group had disease recurrence compared with eight (21.1%) in the vancomycin group between days 15 and 60.
In the FMT group, 11 patients received additional treatment compared with four in the vancomycin group, predominantly oral vancomycin in both groups.
Despite the high rates of severe comorbidity among the patients at baseline, a subgroup analyses showed no significant differences in treatment effects based on factors including sex, age group, Charlson Comorbidity Index score, or CDI severity.
Importantly, there were also no significant differences in adverse events between the groups.
“Our results indicate that it is reasonable to treat patients with primary CDI with FMT and provide antibiotics only to patients with ongoing symptoms or recurrence after FMT,” the authors concluded.
FMT Faces Challenges in the US
FMT specifically consists of direct instillation of fecal matter to the upper gastrointestinal tract, via capsules or duodenal infusion, or the lower gastrointestinal tract via colonoscopy or enema.
While an AGA guideline issued in 2024 endorsed FMT for the prevention of recurrent, refractory, or fulminant CDI in select adults not responding to standard antibiotics, the association underscored important caveats, including a low quality of evidence, and concluded that FMT could not yet be recommended for other gastrointestinal conditions.
The treatment meanwhile has faced an uphill battle in the US. The provision of screened FMT inocula through the nonprofit OpenBiome, previously the country’s largest stool bank, was recently suspended amid FDA policy changes.
And while other commercial-grade biotherapeutic products Rebyota and Vowst, have received FDA approval, cost and insurance coverage can be significant barriers, said Elizabeth Hohmann, MD, of the Infectious Disease Division at Massachusetts General Hospital, Boston, in an editorial published with the study.
“Currently approved options are expensive and are not available to many who might benefit for various reasons, primarily cost,” she said.
Acceptance Higher in Europe
In Europe, and particularly Norway, acceptance of FMT for CDI and other indications has been more favorable, and while regulation of the treatment has varied among European countries, a new regulation to be implemented by the European Union in 2027 will improve standardization of the production, handling, storage, and other factors of FMT, Juul told GI & Hepatology News.
“I believe the new regulations will make the treatment more available to patients, and a standardization of the FMT production will make future trials more comparable and useful across countries,” he said.
Juul said he further expects that “our results will lower the threshold for choosing FMT as treatment in primary infections. I know that Denmark also gives FMT to patients with primary CDI.”
Quality of Life
Hohmann, who has treated many patients with recurrent CDI with FMT, noted that a key factor that should be underscored is how much better patients can feel after the treatment.
“Although there are no quality of life surveys in [the current study], had they been done, I suspect quality of life might have been higher in the FMT group; in my experience, people feel better after microbiome restoration.”
She added that her patients “report feeling much better, and that’s why I keep doing it,” she said. “I’ve had an 80-year-old patient tell me he’s going back to snow shoveling; another saying she can return to yoga classes.”
“When you have had bad gut microbiome dysbiosis that becomes normal, you feel a lot better,” Hohmann said.
In the treatment of primary CDI, however, Hohmann said the prospects, at least in the US, are likely slim.
“I do not believe that we in the United States will see FMT as a primary treatment of C difficile infection anytime soon,” she wrote in the editorial.
Nevertheless, Hohmann asserted that “FMT should remain available, with appropriate sources of carefully screened inocula for care and for further research into the many illnesses and therapies that are influenced by the health of the gut microbiome.”
This study received funding from the South-East Norway Health Trust. Hohmann had no disclosures to report.
A version of this article appeared on Medscape.com.
Withdrawing Anti-TNF in IBD Remission: New Data
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
In the Spanish EXIT study, anti-TNF withdrawal in selected patients with IBD in clinical, endoscopic, and radiological remission had no impact on sustained clinical remission at 1 year, although objective markers of activity were higher in patients who stopped treatment.
The discontinuation of anti-TNF treatment “could be considered as an option” for a selected group of patients, said the authors led by Javier Gisbert, MD, PhD, with Autonomous University of Madrid.
However, the higher proportion of patients with elevated fecal calprotectin and significant endoscopic lesions at the end of follow-up “calls for caution and should be considered when discontinuing treatment in patients,” Gisbert and colleagues concluded.
The EXIT study results were published in the journal Gut (2025 Feb. doi: 10.1136/gutjnl-2024-333385).
Risky Business?
Anti-TNF drugs have reshaped IBD treatment but bring infection risks and costs, prompting interest in planned withdrawal after stable remission.
Yet prior evidence has been mixed. A meta-analysis of 27 studies suggested higher relapse after stopping anti-TNF therapy. However, the results were heterogeneous and most of the studies were retrospective, with a low number of patients and without a control group to compare with.
Clinical trials that have assessed the risk for relapse after discontinuation of anti-TNF therapy generally favored maintenance but had notable limitations.
The EXIT trial was conducted at 33 IBD units across Spain. A total of 140 patients in steroid-free clinical remission for ≥ 6 months on standard-dose infliximab or adalimumab were randomized (1:1) to either continue anti-TNF or switch to placebo matched to the drug they had been taking. All patients continued on immunomodulator therapy.
At 1 year, the proportion of patients with sustained clinical remission (primary outcome) was similar between patients who continued anti-TNF therapy and peers who stopped the medication (76% and 84%, respectively).
However, the proportion of patients with significant endoscopic lesions at the end of follow-up was higher in those who withdrew anti-TNF therapy (19% vs 8.5%; P = .01). Elevated fecal calprotectin (> 250 µg/g) was more common after withdrawal (33% vs 13%; P = .01).
Fecal calprotectin > 250 µg/g at baseline predicted lower odds of sustained remission and higher risk for losing remission — and was the only factor associated with lower likelihood of sustained remission.
Common Clinical Question
“When a patient starts an advanced biologic therapy, they often ask — will I be able to stop it?” Jean-Frederic Colombel, MD, director of the Inflammatory Bowel Disease Clinical Center at the Icahn School of Medicine at Mount Sinai, New York City, who wasn’t involved in the study, told GI & Hepatology News.
Generally speaking, Colombel said he tells patients, “If the drug is working well and you are in deep remission, they should try to avoid stopping because there is a risk of relapse. And with relapse, we never know if the drug will work again and maybe we’ll have to switch to another medication.”
“It’s an individualized discussion and decision and patients who do opt to stop [anti-TNF therapy] need to be monitored closely,” Colombel said.
Colombel cautioned that the study had a relatively short 1-year follow-up and those that stopped anti-TNF therapy had evidence of recurrent inflammation.
“Even though it didn’t translate yet to clinical relapse, there were more patients with subclinical active disease in the group that stopped as compared to the group that continued,” Colombel said.
He also noted that in the SPARE trial of patients with Crohn’s disease in clinical remission, patients who stopped infliximab had a higher risk for relapse compared with patients who stopped azathioprine and those who continued the combination therapy.
The EXIT study was supported by grants from Instituto de Salud Carlos III, Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa and AbbVie. Gisbert reported serving as speaker, consultant, and advisory member for or receiving research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma. Colombel had no relevant disclosures.
A version of this article appeared on Medscape.com.
How Chronic Stress Disrupts the Gut Microbiome
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
Chronic psychological stress is common. A 2023 survey revealed that about one quarter of US adults reported high stress levels, and three quarters reported that chronic stress affects their daily lives.
Emerging evidence suggests that chronic stress not only exacts a high toll on mental health but also can wreak havoc on all levels of gastrointestinal (GI) functioning, all the way down to the microbiome.
Aasma Shaukat, MD, MPH, AGAF, gastroenterologist with NYU Langone Health and director of GI Outcomes Research, Gastroenterology at NYU Grossman School of Medicine in New York City, said in an interview with GI & Hepatology News.
“This basically means that the normal balance of microorganisms that essentially we think are beneficial gets reduced, and the colonies considered to be more harmful proliferate,” she explained.
What Does the Science Tell Us?
Numerous studies published in the past 5 years have linked chronic stress to modest but reproducible shifts in the composition of the microbiome.
A study of frontline healthcare workers during COVID-19 revealed that the pandemic was associated with significant depression, anxiety, and stress, as well as gut dysbiosis that persisted for at least half a year.
Notably, healthcare workers had low gut alpha diversity, indicating a less resilient and diverse microbiome, a state often associated with dysbiosis and increased risk for various diseases and negative health outcomes.
A two-cohort study of healthy adults found higher alpha diversity in those reporting low stress levels. It also found a link between stress and enriched levels of Escherichia/Shigella, an overgrowth of which has been linked to various conditions, including inflammatory bowel disease.
In addition, a 2023 systematic review of human studies concluded that stress is associated with changes in specific genera — namely reductions in gut-healthy Lachnospira/Lachnospiraceae and Phascolarctobacterium, which produce beneficial short-chain fatty acids that support the health of the intestinal lining and modulate the immune system.
Stress during specific life stages also appears to alter the gut microbiome.
For example, in a study of postpartum women, those at an increased risk for parenting stress showed lower alpha diversity on the Shannon diversity index.
Research involving mother-child pairs tied adversity — such as maltreatment of the mother during her childhood, prenatal anxiety, and hardship in the child’s early life — to distinct microbiome profiles in 2-year-olds, supporting a stress-microbiome pathway relevant to socioemotional outcomes, the authors said.
Emerging evidence indicates a link between the gut microbiome and posttraumatic stress disorder (PTSD).
A recent systematic review found differences in gut microbial taxa between individuals with PTSD and trauma-exposed controls without PTSD. A separate analysis pointed to a potential causal impact of gut microbiomes on the development of PTSD.
Mechanisms Behind the Link
Stress interferes with the brain’s production of neurotransmitters, such as serotonin, which controls anxiety, mood, sleep, and many other functions in the brain, Shaukat told GI & Hepatology News.
“But serotonin also crosses the blood-brain barrier, and actually, the gut has more serotonin receptors than the brain, so an imbalance of serotonin can actually affect the gut microbiome through signaling at the neurotransmitter level,” Shaukat explained.
Stress can also affect sleep, and sleep itself has regulatory properties for gut bacteria, Shaukat noted.
“Stress also lowers our immunity, and this can make the gut barrier susceptible or permeable to bacterial toxins that can pass through and breach the gut barrier and be released into the bloodstream, which can trigger inflammation,” Shaukat explained.
Implications for Patient Care
The gut-brain-microbiome axis remains an emerging field of study. “We’re learning more and more about this, and we need to because the microbial colonies are so diverse and we haven’t nailed it down yet,” Shaukat said.
In the meantime, what can clinicians tell patients?
Aside from managing stress, which “is easier said than done,” patients can improve their diet, Shaukat said.
“What we tell patients is to essentially increase their intake of gut-friendly foods that preferentially grow the bacterial colonies that are beneficial for us,” Shaukat said. This includes fermented foods, yogurt, kimchi, chia seeds, kombucha, pickled vegetables, and whole grains.
A recent randomized controlled trial of healthy adults found a “psychobiotic diet” — a diet high in prebiotic and fermented foods — was associated with less perceived stress and subtle beneficial shifts in microbial composition.
“These foods can help keep the gut in good health and may actually also reduce or mitigate some of the effects of stress,” Shaukat said.
“Eating well is something I think we should all think about and maybe prioritize when we’re going through a stressful situation or looking to kind of mitigate the effects of stress and the anxiety and depression it can cause,” she advised.
Shaukat said she also encourages patients to engage in regular physical activity, which benefits the gut microbiome by helping to regulate gut motility. Exercise can also boost mood and help relieve stress.
“A balanced Mediterranean diet and regular activity is truly the secret for gut health,” Shaukat said.
Patients may be tempted by the probiotic supplements lining drugstore shelves, but there “isn’t great evidence for probiotic supplements,” she said. “What we can get from dietary sources far outweighs what can be put in a pill.”
Shaukat disclosed having no relevant disclosures.
A version of this article appeared on Medscape.com.
IBD 101: Intensive Course for GI Fellows Boosts Clinical Confidence
Results from the initial pilot program in 2019, called “IBD 101: Physicians and Patients Providing Pearls and Perspectives” are outlined in Inflammatory Bowel Diseases by Lisa Malter, MD, AGAF, a professor of medicine in the Division of Gastroenterology at NYU Langone Grossman School of Medicine, New York City, and colleagues.
The course, conducted by Malter at NYU Langone’s simulation center, was designed to increase fellows’ early exposure to the complexities of IBD and its diagnosis and management in the context of rapidly changing therapies and variability across US GI training programs. The authors reported that the 2019 program was well received, with attendees showing “increased comfort and sustained benefit” in discussing IBD management with patients. Notably, participants’ increased comfort levels in broaching IBD topics persisted 3 years after the course compared with that of nonparticipating peers, pointing to potential improved patient care after completion of training.
“At this point, 1 in every 100 GI patients has IBD. It’s one of the more complex GI conditions and its incidence and prevalence are increasing globally,” Malter told GI & Hepatology News. Prevalence rates in the US are reportedly as high as 464.5 per 100,000 persons.
“In addition, its management has become more complicated with newer medications and treatments coming on stream,” she said. “An educational gap exists.”
The Program
The course provided an intimate, interactive format with national experts in the field serving as faculty. Course objectives included basic, introductory information on the diagnosis, treatment, and management of IBD; early exposure to IBD as a subspecialty to allow registrants to make informed career decisions; and information about other educational opportunities.
The course was designed to raise participants’ comfort levels in discussing seven topics with patients, including the need for surgery, IBD in pregnancy, treatment escalation in different disease scenarios, and lack of treatment response.
The three-part course, featuring case scenarios, was offered in person to 60 fellows selected by regional GI fellowship program directors and course faculty, which consisted of a director, three codirectors, and 14 local and national IBD experts. A half-day training session for faculty was held immediately before the course.
In September 2019, the first 32 fellows from Accreditation Council for Graduate Medical Education-accredited programs participated in IBD 101. A total of 49 (89%) of 55 participants completed presession and immediate postsession surveys.
In the 3-year follow-up survey, among 36 fellows, of whom 21 (58%) attended IBD 101 and 15 (42%) did not, attendees reported overall IBD confidence and equivalent or higher levels of comfort in discussing each of seven topics.
Among the specific survey findings:
- 100% said the course had improved their ability to effectively treat and manage patients
- A higher proportion of attendees strongly agreed with having comfort in discussing pregnancy in IBD (43% vs 13%; P = .08)
- A statistically significant proportion strongly agreed with having comfort in discussing loss of response to biologics (62% vs 27%; P = .049)
- 98% reported increased interest in exploring IBD during fellowship
- 100% noted improved understanding of supplemental opportunities to learn about IBD
- 96% would strongly recommend this course to future GI fellows
Further testimony to the effectiveness of the ongoing course, said Malter, is that the version offered in 2024 attracted 425 GI fellows from across the country. “That’s about 90% of US GI fellows,” she said.
Offering an outsider’s perspective on the results of the course, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, a director or the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, said, “It’s a useful update. It’s always good to see benefits from educational courses.” He expressed caution, however, “in that a small subset of GI fellows always selects toward those with greater IBD interest. Consequently, they likely have participated in several other IBD education activities in the intervening 3 years — so one can’t attribute benefit to this course alone.”
And while one effect of such courses may to increase the number of IBD-interested trainees, their role in providing IBD education to gastroenterologists who will not specialize in IBD is more important, Ananthakrishnan added. “These general gastroenterologists are going to be managing a lot of the IBD in the community, so in my opinion, ensuring they are comfortable with caring for IBD patients optimally is more important than training IBD specialists, who have many opportunities for education.”
In collaboration with the American College of Gastroenterology, the course is open to all first-year GI fellows training in North America. The most recent program was held on September 13, 2025.
This paper received no specific funding. The IBD course has been supported by unrestricted educational grants from Pfizer and Takeda Pharmaceuticals and sponsorships from AbbVie, Janssen, and Prometheus Labs.Malter reported receiving educational grants from AbbVie, Janssen, Pfizer, and Takeda; serving as a consultant for Abbvie and Pharmacosmos; and serving on the advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Merck, and Takeda. Multiple coauthors disclosed similar relationships with numerous private-sector companies.
A version of this article appeared on Medscape.com.
Results from the initial pilot program in 2019, called “IBD 101: Physicians and Patients Providing Pearls and Perspectives” are outlined in Inflammatory Bowel Diseases by Lisa Malter, MD, AGAF, a professor of medicine in the Division of Gastroenterology at NYU Langone Grossman School of Medicine, New York City, and colleagues.
The course, conducted by Malter at NYU Langone’s simulation center, was designed to increase fellows’ early exposure to the complexities of IBD and its diagnosis and management in the context of rapidly changing therapies and variability across US GI training programs. The authors reported that the 2019 program was well received, with attendees showing “increased comfort and sustained benefit” in discussing IBD management with patients. Notably, participants’ increased comfort levels in broaching IBD topics persisted 3 years after the course compared with that of nonparticipating peers, pointing to potential improved patient care after completion of training.
“At this point, 1 in every 100 GI patients has IBD. It’s one of the more complex GI conditions and its incidence and prevalence are increasing globally,” Malter told GI & Hepatology News. Prevalence rates in the US are reportedly as high as 464.5 per 100,000 persons.
“In addition, its management has become more complicated with newer medications and treatments coming on stream,” she said. “An educational gap exists.”
The Program
The course provided an intimate, interactive format with national experts in the field serving as faculty. Course objectives included basic, introductory information on the diagnosis, treatment, and management of IBD; early exposure to IBD as a subspecialty to allow registrants to make informed career decisions; and information about other educational opportunities.
The course was designed to raise participants’ comfort levels in discussing seven topics with patients, including the need for surgery, IBD in pregnancy, treatment escalation in different disease scenarios, and lack of treatment response.
The three-part course, featuring case scenarios, was offered in person to 60 fellows selected by regional GI fellowship program directors and course faculty, which consisted of a director, three codirectors, and 14 local and national IBD experts. A half-day training session for faculty was held immediately before the course.
In September 2019, the first 32 fellows from Accreditation Council for Graduate Medical Education-accredited programs participated in IBD 101. A total of 49 (89%) of 55 participants completed presession and immediate postsession surveys.
In the 3-year follow-up survey, among 36 fellows, of whom 21 (58%) attended IBD 101 and 15 (42%) did not, attendees reported overall IBD confidence and equivalent or higher levels of comfort in discussing each of seven topics.
Among the specific survey findings:
- 100% said the course had improved their ability to effectively treat and manage patients
- A higher proportion of attendees strongly agreed with having comfort in discussing pregnancy in IBD (43% vs 13%; P = .08)
- A statistically significant proportion strongly agreed with having comfort in discussing loss of response to biologics (62% vs 27%; P = .049)
- 98% reported increased interest in exploring IBD during fellowship
- 100% noted improved understanding of supplemental opportunities to learn about IBD
- 96% would strongly recommend this course to future GI fellows
Further testimony to the effectiveness of the ongoing course, said Malter, is that the version offered in 2024 attracted 425 GI fellows from across the country. “That’s about 90% of US GI fellows,” she said.
Offering an outsider’s perspective on the results of the course, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, a director or the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, said, “It’s a useful update. It’s always good to see benefits from educational courses.” He expressed caution, however, “in that a small subset of GI fellows always selects toward those with greater IBD interest. Consequently, they likely have participated in several other IBD education activities in the intervening 3 years — so one can’t attribute benefit to this course alone.”
And while one effect of such courses may to increase the number of IBD-interested trainees, their role in providing IBD education to gastroenterologists who will not specialize in IBD is more important, Ananthakrishnan added. “These general gastroenterologists are going to be managing a lot of the IBD in the community, so in my opinion, ensuring they are comfortable with caring for IBD patients optimally is more important than training IBD specialists, who have many opportunities for education.”
In collaboration with the American College of Gastroenterology, the course is open to all first-year GI fellows training in North America. The most recent program was held on September 13, 2025.
This paper received no specific funding. The IBD course has been supported by unrestricted educational grants from Pfizer and Takeda Pharmaceuticals and sponsorships from AbbVie, Janssen, and Prometheus Labs.Malter reported receiving educational grants from AbbVie, Janssen, Pfizer, and Takeda; serving as a consultant for Abbvie and Pharmacosmos; and serving on the advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Merck, and Takeda. Multiple coauthors disclosed similar relationships with numerous private-sector companies.
A version of this article appeared on Medscape.com.
Results from the initial pilot program in 2019, called “IBD 101: Physicians and Patients Providing Pearls and Perspectives” are outlined in Inflammatory Bowel Diseases by Lisa Malter, MD, AGAF, a professor of medicine in the Division of Gastroenterology at NYU Langone Grossman School of Medicine, New York City, and colleagues.
The course, conducted by Malter at NYU Langone’s simulation center, was designed to increase fellows’ early exposure to the complexities of IBD and its diagnosis and management in the context of rapidly changing therapies and variability across US GI training programs. The authors reported that the 2019 program was well received, with attendees showing “increased comfort and sustained benefit” in discussing IBD management with patients. Notably, participants’ increased comfort levels in broaching IBD topics persisted 3 years after the course compared with that of nonparticipating peers, pointing to potential improved patient care after completion of training.
“At this point, 1 in every 100 GI patients has IBD. It’s one of the more complex GI conditions and its incidence and prevalence are increasing globally,” Malter told GI & Hepatology News. Prevalence rates in the US are reportedly as high as 464.5 per 100,000 persons.
“In addition, its management has become more complicated with newer medications and treatments coming on stream,” she said. “An educational gap exists.”
The Program
The course provided an intimate, interactive format with national experts in the field serving as faculty. Course objectives included basic, introductory information on the diagnosis, treatment, and management of IBD; early exposure to IBD as a subspecialty to allow registrants to make informed career decisions; and information about other educational opportunities.
The course was designed to raise participants’ comfort levels in discussing seven topics with patients, including the need for surgery, IBD in pregnancy, treatment escalation in different disease scenarios, and lack of treatment response.
The three-part course, featuring case scenarios, was offered in person to 60 fellows selected by regional GI fellowship program directors and course faculty, which consisted of a director, three codirectors, and 14 local and national IBD experts. A half-day training session for faculty was held immediately before the course.
In September 2019, the first 32 fellows from Accreditation Council for Graduate Medical Education-accredited programs participated in IBD 101. A total of 49 (89%) of 55 participants completed presession and immediate postsession surveys.
In the 3-year follow-up survey, among 36 fellows, of whom 21 (58%) attended IBD 101 and 15 (42%) did not, attendees reported overall IBD confidence and equivalent or higher levels of comfort in discussing each of seven topics.
Among the specific survey findings:
- 100% said the course had improved their ability to effectively treat and manage patients
- A higher proportion of attendees strongly agreed with having comfort in discussing pregnancy in IBD (43% vs 13%; P = .08)
- A statistically significant proportion strongly agreed with having comfort in discussing loss of response to biologics (62% vs 27%; P = .049)
- 98% reported increased interest in exploring IBD during fellowship
- 100% noted improved understanding of supplemental opportunities to learn about IBD
- 96% would strongly recommend this course to future GI fellows
Further testimony to the effectiveness of the ongoing course, said Malter, is that the version offered in 2024 attracted 425 GI fellows from across the country. “That’s about 90% of US GI fellows,” she said.
Offering an outsider’s perspective on the results of the course, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, a director or the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston, said, “It’s a useful update. It’s always good to see benefits from educational courses.” He expressed caution, however, “in that a small subset of GI fellows always selects toward those with greater IBD interest. Consequently, they likely have participated in several other IBD education activities in the intervening 3 years — so one can’t attribute benefit to this course alone.”
And while one effect of such courses may to increase the number of IBD-interested trainees, their role in providing IBD education to gastroenterologists who will not specialize in IBD is more important, Ananthakrishnan added. “These general gastroenterologists are going to be managing a lot of the IBD in the community, so in my opinion, ensuring they are comfortable with caring for IBD patients optimally is more important than training IBD specialists, who have many opportunities for education.”
In collaboration with the American College of Gastroenterology, the course is open to all first-year GI fellows training in North America. The most recent program was held on September 13, 2025.
This paper received no specific funding. The IBD course has been supported by unrestricted educational grants from Pfizer and Takeda Pharmaceuticals and sponsorships from AbbVie, Janssen, and Prometheus Labs.Malter reported receiving educational grants from AbbVie, Janssen, Pfizer, and Takeda; serving as a consultant for Abbvie and Pharmacosmos; and serving on the advisory boards for AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Merck, and Takeda. Multiple coauthors disclosed similar relationships with numerous private-sector companies.
A version of this article appeared on Medscape.com.
FDA OKs Tremfya for Ulcerative Colitis
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor available as both SC and intravenous (IV) induction options for the treatment of UC and Crohn’s disease (CD), the company noted in a news release.
The approval of SC guselkumab induction in UC was based on results from the phase 3 ASTRO trial, which randomly allocated 418 patients with moderately to severely active UC to receive either induction with 400 mg SC guselkumab at weeks 0, 4, and 8 or placebo.
Following induction, the treatment group either received a maintenance dose of 200 mg SC guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting at 16 weeks).
All patients had had an inadequate response or intolerance to conventional therapy.
All primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with SC guselkumab compared to placebo across all clinical and endoscopic measures, the company said.
At 12 weeks, a significantly greater proportion of patients treated with 400 mg SC guselkumab every 4 weeks achieved clinical remission (26% vs 7% with placebo; P < .001) and endoscopic improvement (36% vs 12%; P < .001).
The results were consistent with the FDA-approved 200 mg IV induction regimen, which previously achieved clinical remission (23% vs 8% with placebo; P < .001) and endoscopic improvement (27% vs 11%; P < .001).
The efficacy of SC and IV induction was comparable across subgroups with severe or refractory disease and both routes demonstrated a similar time to onset of efficacy.
SC guselkumab induction followed by SC guselkumab maintenance therapy also demonstrated statistically significant and clinically meaningful improvements in clinical remission and endoscopic improvement compared to placebo.
“Historically, IL-23 inhibitors have required IV infusions at the start of therapy, which can create barriers to starting treatment or be burdensome for some patients and clinicians,” study investigator David T. Rubin, MD, AGAF, director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, said in the news release.
“UC patients and providers now have the choice of starting Tremfya with a self-administered subcutaneous injection, with the same efficacy and safety that were established with IV induction in the prior clinical trials and subsequently seen in our real-world practice,” Rubin said.
Full prescribing information and medication guide are available online.
A version of this article appeared on Medscape.com.
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor available as both SC and intravenous (IV) induction options for the treatment of UC and Crohn’s disease (CD), the company noted in a news release.
The approval of SC guselkumab induction in UC was based on results from the phase 3 ASTRO trial, which randomly allocated 418 patients with moderately to severely active UC to receive either induction with 400 mg SC guselkumab at weeks 0, 4, and 8 or placebo.
Following induction, the treatment group either received a maintenance dose of 200 mg SC guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting at 16 weeks).
All patients had had an inadequate response or intolerance to conventional therapy.
All primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with SC guselkumab compared to placebo across all clinical and endoscopic measures, the company said.
At 12 weeks, a significantly greater proportion of patients treated with 400 mg SC guselkumab every 4 weeks achieved clinical remission (26% vs 7% with placebo; P < .001) and endoscopic improvement (36% vs 12%; P < .001).
The results were consistent with the FDA-approved 200 mg IV induction regimen, which previously achieved clinical remission (23% vs 8% with placebo; P < .001) and endoscopic improvement (27% vs 11%; P < .001).
The efficacy of SC and IV induction was comparable across subgroups with severe or refractory disease and both routes demonstrated a similar time to onset of efficacy.
SC guselkumab induction followed by SC guselkumab maintenance therapy also demonstrated statistically significant and clinically meaningful improvements in clinical remission and endoscopic improvement compared to placebo.
“Historically, IL-23 inhibitors have required IV infusions at the start of therapy, which can create barriers to starting treatment or be burdensome for some patients and clinicians,” study investigator David T. Rubin, MD, AGAF, director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, said in the news release.
“UC patients and providers now have the choice of starting Tremfya with a self-administered subcutaneous injection, with the same efficacy and safety that were established with IV induction in the prior clinical trials and subsequently seen in our real-world practice,” Rubin said.
Full prescribing information and medication guide are available online.
A version of this article appeared on Medscape.com.
Guselkumab is the first and only interleukin-23 (IL-23) inhibitor available as both SC and intravenous (IV) induction options for the treatment of UC and Crohn’s disease (CD), the company noted in a news release.
The approval of SC guselkumab induction in UC was based on results from the phase 3 ASTRO trial, which randomly allocated 418 patients with moderately to severely active UC to receive either induction with 400 mg SC guselkumab at weeks 0, 4, and 8 or placebo.
Following induction, the treatment group either received a maintenance dose of 200 mg SC guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting at 16 weeks).
All patients had had an inadequate response or intolerance to conventional therapy.
All primary and secondary endpoints demonstrated statistically significant and clinically meaningful improvements with SC guselkumab compared to placebo across all clinical and endoscopic measures, the company said.
At 12 weeks, a significantly greater proportion of patients treated with 400 mg SC guselkumab every 4 weeks achieved clinical remission (26% vs 7% with placebo; P < .001) and endoscopic improvement (36% vs 12%; P < .001).
The results were consistent with the FDA-approved 200 mg IV induction regimen, which previously achieved clinical remission (23% vs 8% with placebo; P < .001) and endoscopic improvement (27% vs 11%; P < .001).
The efficacy of SC and IV induction was comparable across subgroups with severe or refractory disease and both routes demonstrated a similar time to onset of efficacy.
SC guselkumab induction followed by SC guselkumab maintenance therapy also demonstrated statistically significant and clinically meaningful improvements in clinical remission and endoscopic improvement compared to placebo.
“Historically, IL-23 inhibitors have required IV infusions at the start of therapy, which can create barriers to starting treatment or be burdensome for some patients and clinicians,” study investigator David T. Rubin, MD, AGAF, director of the Inflammatory Bowel Disease Center at University of Chicago Medicine, said in the news release.
“UC patients and providers now have the choice of starting Tremfya with a self-administered subcutaneous injection, with the same efficacy and safety that were established with IV induction in the prior clinical trials and subsequently seen in our real-world practice,” Rubin said.
Full prescribing information and medication guide are available online.
A version of this article appeared on Medscape.com.
Could a Clinical Decision Support Tool Improve Outcomes in Pediatric Diarrhea?
“Clinical decision support tools are designed to assist clinicians in making informed and accurate diagnostic and prognostic decisions using available characteristics of the patient and the larger context,” Anna Jones, MD, MPH, and her colleagues wrote in JAMA Network Open.
Jones is in the Department of Pediatrics at the University of Utah School of Medicine in Salt Lake City.
Jones and her coauthors concluded such a tool had the potential to improve evidence-based testing in pediatric diarrhea and help clinicians communicate clearly to parents the etiology of their child’s illness. Parents in the study, however, expressed skepticism over the tool, voicing concerns that physicians might over-rely on its algorithms.
The authors said that thanks to the development of multiplex polymerase chain reaction (PCR) panels for gastroenteritis, it is now possible to quickly identify up to 22 different pathogens from stool samples. What is lacking, they suggested, are protocols for knowing when to test for these pathogens.
“Although the Infectious Diseases Society of America 2017 clinical practice guidelines for the diagnosis and management of infectious diarrhea provide broad recommendations for when diarrhea-related diagnostics should be used, clear guidelines specific to the use of multiplex PCR panels do not exist,” Jones and her coauthors wrote, adding that misusing the diagnostics, however, “can lead to inappropriate antibiotic use and excess financial burdens.”
Meanwhile, communication breakdowns in the patient-doctor relationship are a leading contributor to diagnostic errors, according to the Agency for Healthcare Research and Quality. Subsequently, the National Academy of Medicine has recommended that healthcare professionals seek to engage patients and their families in the diagnostic process.
With these factors in mind, Jones and her colleagues recruited parents who had sought care for their child’s diarrhea and clinicians who routinely treat children with diarrhea. The recruits came from five urgent care sites and one emergency department (ED), all in Utah. Participants were interviewed between June 15, 2023, and January 24, 2025.
In all, the authors interviewed 44 parents (40 women; median age, 34 years). One parent (2%) identified as Asian, two (5%) as Black or African American, 15 (34%) as Hispanic or Latin, and 22 (50%) as White individuals. The remaining four participants (9%) were of unknown race and ethnicity. Most parents spoke English as their primary language (40 [91%]).
Among the 16 clinicians, 10 were physicians and six were nurse practitioners or physician associates. Eleven of the 16 were women and the group had a median age of 42 years. Fourteen clinicians (88%) self-identified as White individuals and two (13%) had unknown race and ethnicity.
All were interviewed on their management of pediatric diarrhea and about their expectations for diagnostic testing and treatment of the condition, as well as the perceived utility of a clinical decision support tool.
Jones and colleagues identified three motivations among parents who sought clinical care for a child with diarrhea. The first was reassurance, which the authors said included validation for what the parents were already doing to care for their child.
The second motivation was to obtain insight into the etiology of their child’s symptoms. “Many believed that diagnostic testing to identify the specific etiology of the illness would be useful. Parents indicated that knowing the etiology would offer desired reassurance and potentially inform treatment decisions,” Jones and her coauthors wrote.
Lastly, parents sought appropriate treatment and symptom relief.
Many clinicians acknowledged the benefits of a clinical decision support tool for help with evidence-based decision-making during diagnosis and to facilitate communication with families. However, they expressed skepticism over the use of diagnostics for etiology, noting that disease management was not dependent upon knowing it.
Some clinicians said many families expected a test. “Even if I don’t think that a GI [gastrointestinal] stool study is necessary, there are situations where…a family is not going to leave the [ED] happy without one. And so I probably order them sometimes when they’re not truly indicated,” a physician reported in the interview.
“That said,” Jones and her coauthors wrote, “clinicians thought that diagnostic testing for pediatric diarrhea was generally not warranted, except in unique cases [such as] bloody stools, prolonged duration of diarrhea, or travel history.”
Many clinicians thought a decision-making tool might help build trust and rapport with the patient’s family, reassuring them their child is getting evidence-based care.
“It just adds to that shared decision-making model. I think it adds trust…I think it does kind of back up our ability to defend why we’re doing what we’re doing,” reported one surveyed ED physician.
Parents were mostly wary of the potential use of a clinical decision-making tool. Jones and colleagues reported that in addition to some clinicians, “several parents expressed concerns that a tool does not account for nuances and would lead to ‘generalizing every kid’ (said the father of a child aged 1-3 years), as opposed to providing patient-centered care.”
Parents also said they worried a clinician would not reply upon their own clinical judgement if they had a diagnostic tool.
Jones and her colleagues concluded that before implementing a clinical decision support tool in pediatric diarrhea, strategies are necessary to, “resolve tension in care expectations, facilitate diagnostic stewardship, and optimize care.”
In an accompanying editorial, KC Coffey, MD, MPH, concluded that the study by Jones and colleagues suggests that adapting such tools to incorporate parental expectations, “could facilitate patient engagement in the diagnostic process and increase acceptance of [using these tools for] decisions. Such discussions might also raise awareness of the potential harms of over testing.” Coffey is an epidemiologist and infectious disease physician at the University of Maryland in Baltimore.
Elizabeth Dobler, MD, who was not involved in the study, told GI & Hepatology News that “as the number of available tests continues to grow, stewardship is becoming more relevant than ever. Families may not always realize the downsides of unnecessary testing — such as false positives, avoidable procedures, or added risks — and part of our responsibility is to help them understand both the potential benefits and the potential harms of these tests.”
Dobler is the medical director for clinical decision support in the Department of Clinical Informatics at Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago.
Clinical decision support tools are helpful in the clinical setting, Dobler said because “they give providers quick access to the most relevant information needed for decision-making. This includes patient-specific details — symptoms, history, labs, and vitals” as well as the characteristics and downsides of the tests. In an ideal world, she said, clinicians would consider these data for every patient.
Dobler cautioned however, that, “it’s important to stress that these tools don’t replace clinical judgment — the provider still evaluates the patient, considers the clinical context, and incorporates the family’s preferences. But as a complement to that process, I believe these tools are very valuable.”
Lastly, Dobler said that transparency is key to helping parents overcome their hesitancy regarding these tools.
Jones, Coffey, and Dobler reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
“Clinical decision support tools are designed to assist clinicians in making informed and accurate diagnostic and prognostic decisions using available characteristics of the patient and the larger context,” Anna Jones, MD, MPH, and her colleagues wrote in JAMA Network Open.
Jones is in the Department of Pediatrics at the University of Utah School of Medicine in Salt Lake City.
Jones and her coauthors concluded such a tool had the potential to improve evidence-based testing in pediatric diarrhea and help clinicians communicate clearly to parents the etiology of their child’s illness. Parents in the study, however, expressed skepticism over the tool, voicing concerns that physicians might over-rely on its algorithms.
The authors said that thanks to the development of multiplex polymerase chain reaction (PCR) panels for gastroenteritis, it is now possible to quickly identify up to 22 different pathogens from stool samples. What is lacking, they suggested, are protocols for knowing when to test for these pathogens.
“Although the Infectious Diseases Society of America 2017 clinical practice guidelines for the diagnosis and management of infectious diarrhea provide broad recommendations for when diarrhea-related diagnostics should be used, clear guidelines specific to the use of multiplex PCR panels do not exist,” Jones and her coauthors wrote, adding that misusing the diagnostics, however, “can lead to inappropriate antibiotic use and excess financial burdens.”
Meanwhile, communication breakdowns in the patient-doctor relationship are a leading contributor to diagnostic errors, according to the Agency for Healthcare Research and Quality. Subsequently, the National Academy of Medicine has recommended that healthcare professionals seek to engage patients and their families in the diagnostic process.
With these factors in mind, Jones and her colleagues recruited parents who had sought care for their child’s diarrhea and clinicians who routinely treat children with diarrhea. The recruits came from five urgent care sites and one emergency department (ED), all in Utah. Participants were interviewed between June 15, 2023, and January 24, 2025.
In all, the authors interviewed 44 parents (40 women; median age, 34 years). One parent (2%) identified as Asian, two (5%) as Black or African American, 15 (34%) as Hispanic or Latin, and 22 (50%) as White individuals. The remaining four participants (9%) were of unknown race and ethnicity. Most parents spoke English as their primary language (40 [91%]).
Among the 16 clinicians, 10 were physicians and six were nurse practitioners or physician associates. Eleven of the 16 were women and the group had a median age of 42 years. Fourteen clinicians (88%) self-identified as White individuals and two (13%) had unknown race and ethnicity.
All were interviewed on their management of pediatric diarrhea and about their expectations for diagnostic testing and treatment of the condition, as well as the perceived utility of a clinical decision support tool.
Jones and colleagues identified three motivations among parents who sought clinical care for a child with diarrhea. The first was reassurance, which the authors said included validation for what the parents were already doing to care for their child.
The second motivation was to obtain insight into the etiology of their child’s symptoms. “Many believed that diagnostic testing to identify the specific etiology of the illness would be useful. Parents indicated that knowing the etiology would offer desired reassurance and potentially inform treatment decisions,” Jones and her coauthors wrote.
Lastly, parents sought appropriate treatment and symptom relief.
Many clinicians acknowledged the benefits of a clinical decision support tool for help with evidence-based decision-making during diagnosis and to facilitate communication with families. However, they expressed skepticism over the use of diagnostics for etiology, noting that disease management was not dependent upon knowing it.
Some clinicians said many families expected a test. “Even if I don’t think that a GI [gastrointestinal] stool study is necessary, there are situations where…a family is not going to leave the [ED] happy without one. And so I probably order them sometimes when they’re not truly indicated,” a physician reported in the interview.
“That said,” Jones and her coauthors wrote, “clinicians thought that diagnostic testing for pediatric diarrhea was generally not warranted, except in unique cases [such as] bloody stools, prolonged duration of diarrhea, or travel history.”
Many clinicians thought a decision-making tool might help build trust and rapport with the patient’s family, reassuring them their child is getting evidence-based care.
“It just adds to that shared decision-making model. I think it adds trust…I think it does kind of back up our ability to defend why we’re doing what we’re doing,” reported one surveyed ED physician.
Parents were mostly wary of the potential use of a clinical decision-making tool. Jones and colleagues reported that in addition to some clinicians, “several parents expressed concerns that a tool does not account for nuances and would lead to ‘generalizing every kid’ (said the father of a child aged 1-3 years), as opposed to providing patient-centered care.”
Parents also said they worried a clinician would not reply upon their own clinical judgement if they had a diagnostic tool.
Jones and her colleagues concluded that before implementing a clinical decision support tool in pediatric diarrhea, strategies are necessary to, “resolve tension in care expectations, facilitate diagnostic stewardship, and optimize care.”
In an accompanying editorial, KC Coffey, MD, MPH, concluded that the study by Jones and colleagues suggests that adapting such tools to incorporate parental expectations, “could facilitate patient engagement in the diagnostic process and increase acceptance of [using these tools for] decisions. Such discussions might also raise awareness of the potential harms of over testing.” Coffey is an epidemiologist and infectious disease physician at the University of Maryland in Baltimore.
Elizabeth Dobler, MD, who was not involved in the study, told GI & Hepatology News that “as the number of available tests continues to grow, stewardship is becoming more relevant than ever. Families may not always realize the downsides of unnecessary testing — such as false positives, avoidable procedures, or added risks — and part of our responsibility is to help them understand both the potential benefits and the potential harms of these tests.”
Dobler is the medical director for clinical decision support in the Department of Clinical Informatics at Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago.
Clinical decision support tools are helpful in the clinical setting, Dobler said because “they give providers quick access to the most relevant information needed for decision-making. This includes patient-specific details — symptoms, history, labs, and vitals” as well as the characteristics and downsides of the tests. In an ideal world, she said, clinicians would consider these data for every patient.
Dobler cautioned however, that, “it’s important to stress that these tools don’t replace clinical judgment — the provider still evaluates the patient, considers the clinical context, and incorporates the family’s preferences. But as a complement to that process, I believe these tools are very valuable.”
Lastly, Dobler said that transparency is key to helping parents overcome their hesitancy regarding these tools.
Jones, Coffey, and Dobler reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
“Clinical decision support tools are designed to assist clinicians in making informed and accurate diagnostic and prognostic decisions using available characteristics of the patient and the larger context,” Anna Jones, MD, MPH, and her colleagues wrote in JAMA Network Open.
Jones is in the Department of Pediatrics at the University of Utah School of Medicine in Salt Lake City.
Jones and her coauthors concluded such a tool had the potential to improve evidence-based testing in pediatric diarrhea and help clinicians communicate clearly to parents the etiology of their child’s illness. Parents in the study, however, expressed skepticism over the tool, voicing concerns that physicians might over-rely on its algorithms.
The authors said that thanks to the development of multiplex polymerase chain reaction (PCR) panels for gastroenteritis, it is now possible to quickly identify up to 22 different pathogens from stool samples. What is lacking, they suggested, are protocols for knowing when to test for these pathogens.
“Although the Infectious Diseases Society of America 2017 clinical practice guidelines for the diagnosis and management of infectious diarrhea provide broad recommendations for when diarrhea-related diagnostics should be used, clear guidelines specific to the use of multiplex PCR panels do not exist,” Jones and her coauthors wrote, adding that misusing the diagnostics, however, “can lead to inappropriate antibiotic use and excess financial burdens.”
Meanwhile, communication breakdowns in the patient-doctor relationship are a leading contributor to diagnostic errors, according to the Agency for Healthcare Research and Quality. Subsequently, the National Academy of Medicine has recommended that healthcare professionals seek to engage patients and their families in the diagnostic process.
With these factors in mind, Jones and her colleagues recruited parents who had sought care for their child’s diarrhea and clinicians who routinely treat children with diarrhea. The recruits came from five urgent care sites and one emergency department (ED), all in Utah. Participants were interviewed between June 15, 2023, and January 24, 2025.
In all, the authors interviewed 44 parents (40 women; median age, 34 years). One parent (2%) identified as Asian, two (5%) as Black or African American, 15 (34%) as Hispanic or Latin, and 22 (50%) as White individuals. The remaining four participants (9%) were of unknown race and ethnicity. Most parents spoke English as their primary language (40 [91%]).
Among the 16 clinicians, 10 were physicians and six were nurse practitioners or physician associates. Eleven of the 16 were women and the group had a median age of 42 years. Fourteen clinicians (88%) self-identified as White individuals and two (13%) had unknown race and ethnicity.
All were interviewed on their management of pediatric diarrhea and about their expectations for diagnostic testing and treatment of the condition, as well as the perceived utility of a clinical decision support tool.
Jones and colleagues identified three motivations among parents who sought clinical care for a child with diarrhea. The first was reassurance, which the authors said included validation for what the parents were already doing to care for their child.
The second motivation was to obtain insight into the etiology of their child’s symptoms. “Many believed that diagnostic testing to identify the specific etiology of the illness would be useful. Parents indicated that knowing the etiology would offer desired reassurance and potentially inform treatment decisions,” Jones and her coauthors wrote.
Lastly, parents sought appropriate treatment and symptom relief.
Many clinicians acknowledged the benefits of a clinical decision support tool for help with evidence-based decision-making during diagnosis and to facilitate communication with families. However, they expressed skepticism over the use of diagnostics for etiology, noting that disease management was not dependent upon knowing it.
Some clinicians said many families expected a test. “Even if I don’t think that a GI [gastrointestinal] stool study is necessary, there are situations where…a family is not going to leave the [ED] happy without one. And so I probably order them sometimes when they’re not truly indicated,” a physician reported in the interview.
“That said,” Jones and her coauthors wrote, “clinicians thought that diagnostic testing for pediatric diarrhea was generally not warranted, except in unique cases [such as] bloody stools, prolonged duration of diarrhea, or travel history.”
Many clinicians thought a decision-making tool might help build trust and rapport with the patient’s family, reassuring them their child is getting evidence-based care.
“It just adds to that shared decision-making model. I think it adds trust…I think it does kind of back up our ability to defend why we’re doing what we’re doing,” reported one surveyed ED physician.
Parents were mostly wary of the potential use of a clinical decision-making tool. Jones and colleagues reported that in addition to some clinicians, “several parents expressed concerns that a tool does not account for nuances and would lead to ‘generalizing every kid’ (said the father of a child aged 1-3 years), as opposed to providing patient-centered care.”
Parents also said they worried a clinician would not reply upon their own clinical judgement if they had a diagnostic tool.
Jones and her colleagues concluded that before implementing a clinical decision support tool in pediatric diarrhea, strategies are necessary to, “resolve tension in care expectations, facilitate diagnostic stewardship, and optimize care.”
In an accompanying editorial, KC Coffey, MD, MPH, concluded that the study by Jones and colleagues suggests that adapting such tools to incorporate parental expectations, “could facilitate patient engagement in the diagnostic process and increase acceptance of [using these tools for] decisions. Such discussions might also raise awareness of the potential harms of over testing.” Coffey is an epidemiologist and infectious disease physician at the University of Maryland in Baltimore.
Elizabeth Dobler, MD, who was not involved in the study, told GI & Hepatology News that “as the number of available tests continues to grow, stewardship is becoming more relevant than ever. Families may not always realize the downsides of unnecessary testing — such as false positives, avoidable procedures, or added risks — and part of our responsibility is to help them understand both the potential benefits and the potential harms of these tests.”
Dobler is the medical director for clinical decision support in the Department of Clinical Informatics at Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago.
Clinical decision support tools are helpful in the clinical setting, Dobler said because “they give providers quick access to the most relevant information needed for decision-making. This includes patient-specific details — symptoms, history, labs, and vitals” as well as the characteristics and downsides of the tests. In an ideal world, she said, clinicians would consider these data for every patient.
Dobler cautioned however, that, “it’s important to stress that these tools don’t replace clinical judgment — the provider still evaluates the patient, considers the clinical context, and incorporates the family’s preferences. But as a complement to that process, I believe these tools are very valuable.”
Lastly, Dobler said that transparency is key to helping parents overcome their hesitancy regarding these tools.
Jones, Coffey, and Dobler reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
Are Probiotics for Pouchitis Prevention Worth the Cost?
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
, but its cost-effectiveness depends on relapse risk and may only be justified in patients who experience frequent relapses of pouchitis, a new analysis showed.
“Our findings highlight that while probiotic treatments can reduce the risk of this complication, their high costs limit their overall value for most patients,” lead author Gaurav Syal, MD, a gastroenterologist at UCLA Health, said in a statement.
“Our analysis can help guide shared decision-making between patients, clinicians, and payers to ensure resources are used where they can provide the most benefit,” Syal added.
The study was published online in Gastro Hep Advances.
Common Complication After Ulcerative Colitis Surgery
Pouchitis is a common complication in patients with ulcerative colitis who undergo restorative proctocolectomy with IPAA, with a cumulative incidence of around 48% at 2 years and 80% at 30 years.
Many patients who experience pouchitis have a single episode and respond well to short antibiotic courses. However, others develop recurrent or relapsing pouchitis, and 17% progress to a chronic form that can become dependent on antibiotics or refractory to antibiotics.
An eight-strain probiotic was shown to be effective in primary and secondary prevention of pouchitis in randomized, placebo-controlled trials.
Syal and colleagues sought to determine whether it’s worth the cost.
They constructed decision-tree models with Markov simulations to compare the risk for initial development and recurrence of pouchitis over a 2-year period between no prophylaxis and daily use of the eight-strain probiotic.
In the primary prophylaxis model, the cycle length was 2 weeks and pouchitis treatment sequence was ciprofloxacin, metronidazole and ciprofloxacin-tinidazole. In the secondary prophylaxis model, the cycle length was 4 weeks and pouchitis treatment sequence was initially the same as the primary prophylaxis model with the addition of vedolizumab and infliximab.
Costs were calculated from a US third-party payer perspective, using a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY).
For primary prevention, the probiotic slightly increased QALYs compared with no probiotic (0.927 vs 0.918) but at a far higher cost ($2223 vs $299), resulting in an incremental cost-effectiveness ratio (ICER) of $236,076 per QALY — well above the accepted threshold.
In patients with infrequent relapses, probiotic use was slightly more effective than no use of probiotic (cumulative QALYs, 1.26 vs 1.24) but more expensive ($3370 vs $557), yielding an ICER of $153,011 per QALY — again above the accepted threshold.
However, sensitivity analyses revealed that the probiotic was cost-effective in patients with frequent relapsing pouchitis — defined as two or more episodes per year.
In this subgroup, the ICER dropped below the willingness-to-pay threshold of $100,000 per QALY, and in some scenarios, the probiotic even became the dominant strategy, meaning it was both more effective and less costly than no prophylaxis, the researchers noted.
Current guidelines from AGA on managing pouchitis suggest using probiotics to prevent recurrent episodes of pouchitis with a caveat that those who experience infrequent episodes may choose to avoid secondary prevention strategies.
“Our findings supplement the guidelines by confirming that the eight-strain probiotics can be cost-effective in frequent relapsing not in infrequent relapsing pouchitis,” the authors wrote.
They also noted that the probiotic cost itself was the biggest driver of results, accounting for 95% of the total cost in the primary prevention model. According to their analysis, reducing its price by half could make it a cost-effective option more broadly.
They also noted that probiotic prophylaxis could be cost-effective for patients at higher-than-average risk, such as those with primary sclerosing cholangitis (PSC), who have 4.2 times higher odds of developing pouchitis than peers without PSC.
But they cautioned that “further research is warranted on the effectiveness of the eight-strain probiotic for primary prevention of pouchitis in patients with ulcerative colitis and IPAA and PSC.”
The study had no financial support. Syal reported receiving research support from Pfizer.
A version of this article appeared on Medscape.com.
FROM GASTRO HEP ADVANCES
Large Language Models Cut Time, Cost of Guideline Development
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
Ethan Goh, MD, executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, described the AGA pilot as both timely and promising.
“I’m certainly bullish about the use case,” he said in an interview. “Their study design and application is also robust, so I would congratulate them.”
Goh, a general editor for BMJ Digital Health & AI, predicted “huge potential” in the strategy for both clinicians and the general population, who benefit from the most up-to-date guidelines possible.
“I believe that using AI can represent a much faster, more cost effective, efficient way of gathering all these information sources,” he said.
Still, humans will need to be involved in the process.
“[This AI-driven approach] will always need some degree of expert oversight and judgement,” Goh said.
Speaking more broadly about automating study aggregation, Goh said AI may still struggle to determine which studies are most clinically relevant.
“When we use [AI models] to pull out medical references, anecdotally, I don’t think they’re always getting the best ones all the time, or even necessarily the right ones,” he said.
And as AI models grow more impressive, these shortcomings become less apparent, potentially lulling humans into overconfidence.
“Humans are humans,” Goh said. “We get lazy over time. That will be one of the challenges. As the systems get increasingly good, humans start to defer more and more of their judgment to them and say, ‘All right, AI, you’re doing good. Just do 100% automation.’ And then [people] start fact checking or reviewing even less.”
AI could also undermine automated reviews in another way: AI-generated publications that appear genuine, but aren’t, may creep into the dataset.
Despite these concerns, Goh concluded on an optimistic note.
“I think that there are huge ways to use AI, tools, not to replace, but to augment and support human judgment,” he said.
Ethan Goh, MD, is senior research engineer and executive director of the Stanford AI Research and Science Evaluation (ARISE) Network, at Stanford (Calif.) University. He declared no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
, according to a pilot study from the American Gastroenterological Association (AGA).
Faster, cheaper study screening could allow societies to update clinical recommendations more frequently, improving alignment with the latest evidence, lead author Sunny Chung, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues, reported.
“Each guideline typically requires 5 to 15 systematic reviews, making the process time-consuming (averaging more than 60 weeks) and costly (more than $140,000),” the investigators wrote in Gastroenterology . “One of the most critical yet time-consuming steps in systematic reviews is title and abstract screening. LLMs have the potential to make this step more efficient.”
To test this approach, the investigators developed, validated, and applied a dual-model LLM screening pipeline with human-in-the-loop oversight, focusing on randomized controlled trials in AGA guidelines.
The system was built using the 2021 guideline on moderate-to-severe Crohn’s disease, targeting biologic therapies for induction and maintenance of remission.
Using chain-of-thought prompting and structured inclusion criteria based on the PICO framework, the investigators deployed GPT-4o (OpenAI) and Gemini-1.5-Pro (Google DeepMind) as independent screeners, each assessing titles and abstracts according to standardized logic encoded in JavaScript Object Notation. This approach mimicked a traditional double-reviewer system.
After initial testing, the pipeline was validated in a 2025 update of the same guideline, this time spanning 6 focused clinical questions on advanced therapies and immunomodulators. Results were compared against manual screening by 2 experienced human reviewers, with total screening time documented.
The system was then tested across 4 additional guideline topics: fecal microbiota transplantation (FMT) for irritable bowel syndrome and Clostridioides difficile, gastroparesis, and hepatocellular carcinoma. A final test applied the system to a forthcoming guideline on complications of acute pancreatitis.
Across all topics, the dual-LLM system achieved 100% sensitivity in identifying randomized controlled trials (RCTs). For the 2025 update of the AGA guideline on Crohn’s disease, the models flagged 418 of 4,377 abstracts for inclusion, captur-ing all 25 relevant RCTs in just 48 minutes. Manual screening of the same dataset previously took almost 13 hours.
Comparable accuracy and time savings were observed for the other topics.
The pipeline correctly flagged all 13 RCTs in 4,820 studies on FMT for irritable bowel syndrome, and all 16 RCTs in 5,587 studies on FMT for Clostridioides difficile, requiring 27 and 66 minutes, respectively. Similarly, the system captured all 11 RCTs in 3,919 hepatocellular carcinoma abstracts and all 18 RCTs in 1,578 studies on gastroparesis, completing each task in under 65 minutes. Early testing on the upcoming guideline for pancreatitis yielded similar results.
Cost analysis underscored the efficiency of this approach. At an estimated $175–200 per hour for expert screeners, traditional abstract screening would cost around $2,500 per review, versus approximately $100 for the LLM approach—a 96% reduction.
The investigators cautioned that human oversight remains necessary to verify the relevance of studies flagged by the models. While the system’s sensitivity was consistent, it also selected articles that were ultimately excluded by expert reviewers. Broader validation will be required to assess performance across non-RCT study designs, such as observational or case-control studies, they added.
“As medical literature continues to expand, the integration of artificial intelligence into evidence synthesis processes will become increasingly vital,” Dr. Chung and colleagues wrote. “With further refinement and broader validation, this LLM-based pipeline has the potential to revolutionize evidence synthesis and set a new standard for guideline development.”
This study was funded by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. The investigators reported no conflicts of interest.
FROM GASTROENTEROLOGY