Will Pass

The American Gastroenterological Association recently published a Clinical Practice Update Commentary outlining surveillance strategies following endoscopic submucosal dissection (ESD) of dysplasia and early gastrointestinal cancer considered pathologically curative.

The suggested practice advice, which was put together by Andrew Y. Wang, MD, of the University of Virginia, Charlottesville, and colleagues, offers timelines and modalities of surveillance based on neoplasia type and location, with accompanying summaries of relevant literature.

“Long-term U.S. data about ESD outcomes for early GI neoplasia are only beginning to emerge,” the authors wrote in Gastroenterology. “As such, the current clinical practice regarding endoscopic surveillance intervals and the need for other testing (such as radiographic imaging) after ESD considered curative by histopathology is extrapolated from data derived from Asia and other countries, from concepts learned from polypectomy and piecemeal endoscopic mucosal resection (EMR), and from guideline recommendations after local surgical resection.”

The authors went on to suggest that current recommendations for post-ESD surveillance, including international guidelines “are based more so on expert opinion than rigorous evidence.”

The present update was written to offer additional clarity in this area by providing “a reasonable framework for clinical care and launch points for future research to refine and standardize optimal post-ESD surveillance strategies.”

Foremost, Dr. Wang and colleagues suggested that post-ESD surveillance is necessary because of a lack of standardization concerning the definition of complete resection, along with variable standards of pathological assessment in Western countries, compared with Japan, where pathologists use 2-3 mm serial sectioning and special stains to detect lymphovascular invasion, “which is essential to accurate histopathologic diagnosis and determination of curative resection.”

According to the authors, surveillance endoscopy should be performed with a high-definition endoscope augmented with dye-based or electronic chromoendoscopy, and ideally with optimal magnification.

“Although no supporting data are available at this time, it is prudent and may be reasonable to obtain central and peripheral biopsies of the post-ESD scar,” the authors wrote, noting that relevant mucosa should be checked for metachronous lesions.
 

Esophageal dysplasia and esophageal squamous cell carcinoma

Following curative resection of low-grade or high-grade esophageal squamous dysplasia, the authors suggested follow-up esophagogastroduodenoscopy (EGD) initially at intervals of 6-12 months, while advising against endoscopic ultrasonography and radiographic surveillance.

In contrast, Dr. Wang and colleagues suggested that superficial esophageal squamous cell carcinoma removed by ESD may benefit from a shorter interval of endoscopic surveillance, with a range of 3-6 months for first and second follow-up EGDs. Clinicians may also consider endoscopic ultrasonography with each EGD, plus an annual CT scan of the abdomen and chest, for 3-5 years.

“A limitation of ESD is that the at-risk esophagus is left in place, and there is a possibility of developing local recurrence or metachronous neoplasia,” the authors wrote. “Although local recurrence after ESD deemed pathologically curative of esophageal squamous cell carcinoma is infrequent, the development of metachronous lesions is not.”
 

Barrett’s dysplasia and esophageal adenocarcinoma

For all patients, curative removal of Barrett’s dysplasia or esophageal adenocarcinoma should be followed by endoscopy with mucosal ablative therapy at 2-3 months, with treatments every 2-3 months until complete eradication of intestinal metaplasia is achieved, according to Dr. Wang and colleagues.

After complete eradication, patients should be endoscopically screened from 3-12 months, depending on the degree of dysplasia or T-stage of adenocarcinoma, followed by screening procedures ranging from 6 months to 3 years, again depending on disease type.

“Endoscopic resection of visible Barrett’s neoplasia without treatment of Barrett’s esophagus has been associated with significant recurrence rates, so the objective of treatment should be endoscopic resection of visible or nodular dysplasia, followed by complete ablation of any remaining Barrett’s esophagus and associated (flat and/or invisible) dysplasia,” the authors wrote.
 

Gastric dysplasia and gastric adenocarcinoma

According to the update, after curative resection of gastric dysplasia, first follow-up endoscopy should be conducted at 6-12 months. Second follow-up should be conducted at 12 months for low-grade dysplasia versus 6-12 months for high-grade dysplasia, with annual exams thereafter.

For T1a early gastric cancer, the first two follow-up endoscopies should be performed at 6-month intervals, followed by annual exams. T1b Sm1 disease should be screened more aggressively, with 3-6 months intervals for first and second follow-up EGDs, plus CT scans of the abdomen and chest and/or endoscopic ultrasound every 6-12 months for 3-5 years.

“For lesions where a curative resection was achieved based on clinical criteria and histopathologic examination, surveillance is performed primarily to detect metachronous gastric cancers,” the authors wrote.
 

Colonic dysplasia and adenocarcinoma

According to the authors, adenomas with low-grade dysplasia or serrated sessile lesions without dysplasia removed by ESD should be rechecked by colonoscopy at 1 year and then 3 years, followed by adherence to U.S. Multi-Society Task Force recommendations.

For traditional serrated adenomas, serrated sessile lesions with dysplasia, adenomas with high-grade dysplasia, carcinoma in situ, intramucosal carcinoma, or dysplasia in the setting of inflammatory bowel disease, first follow-up colonoscopy should be conducted at 6-12 months, 1 year later, then 3 years after that, followed by reversion to USMSTF recommendations, although patients with IBD may benefit from annual colonoscopy.

Finally, patients with superficial T1 colonic adenocarcinoma should be screened more frequently, with colonoscopies at 3-6 months, 6 months, and 1 year, followed by adherence to USMSTF recommendations.

“The current Japanese guideline suggests that recurrence or metastasis after endoscopic resection of T1 (Sm) colonic carcinomas occurs mainly within 3-5 years,” the authors noted.
 

Rectal dysplasia and adenocarcinoma

Best practice advice suggestions for rectal dysplasia and adenocarcinoma are grouped similarly to the above advice for colonic lesions.

For lower-grade lesions, first follow-up with flexible sigmoidoscopy is suggested after 1 year, then 3 years, followed by reversion to USMSTF recommendations. Higher-grade dysplastic lesions should be checked after 6-12 months, 1 year, then 3 years, followed by adherence to USMSTF guidance, again excluding patients with IBD, who may benefit from annual exams.

Patients with superficial T1 rectal adenocarcinoma removed by ESD deemed pathologically curative should be checked with flexible sigmoidoscopy at 3-6 months, again at 3-6 months after first sigmoidoscopy, then every 6 months for a total of 5 years from the time of ESD, followed by adherence to USMSTF recommendations. At 1 year following ESD, patients should undergo colonoscopy, which can take the place of one of the follow-up flexible sigmoidoscopy exams; if an advanced adenoma is found, colonoscopy should be repeated after 1 year, versus 3 years if no advanced adenomas are found, followed by adherence to USMSTF recommendations. Patients with superficial T1 rectal adenocarcinoma should also undergo endoscopic ultrasound or pelvic MRI with contrast every 3-6 months for 2 years, followed by intervals of 6 months for a total of 5 years. Annual CT of the chest and abdomen may also be considered for a duration of 3-5 years.

Call for research

Dr. Wang and colleagues concluded their update with a call for research.

“We acknowledge that the level of evidence currently available to support much of our surveillance advice is generally low,” they wrote. “The intent of this clinical practice update was to propose surveillance strategies after potentially curative ESD for various GI neoplasms, which might also serve as reference points to stimulate research that will refine future clinical best practice advice.”

The article was supported by the AGA. The authors disclosed relationships with MicroTech, Olympus, Lumendi, U.S. Endoscopy, Boston Scientific, Steris and others.

This article was updated Dec. 15, 2021.

The American Gastroenterological Association recently published a Clinical Practice Update Commentary outlining surveillance strategies following endoscopic submucosal dissection (ESD) of dysplasia and early gastrointestinal cancer considered pathologically curative.

The suggested practice advice, which was put together by Andrew Y. Wang, MD, of the University of Virginia, Charlottesville, and colleagues, offers timelines and modalities of surveillance based on neoplasia type and location, with accompanying summaries of relevant literature.

“Long-term U.S. data about ESD outcomes for early GI neoplasia are only beginning to emerge,” the authors wrote in Gastroenterology. “As such, the current clinical practice regarding endoscopic surveillance intervals and the need for other testing (such as radiographic imaging) after ESD considered curative by histopathology is extrapolated from data derived from Asia and other countries, from concepts learned from polypectomy and piecemeal endoscopic mucosal resection (EMR), and from guideline recommendations after local surgical resection.”

The authors went on to suggest that current recommendations for post-ESD surveillance, including international guidelines “are based more so on expert opinion than rigorous evidence.”

The present update was written to offer additional clarity in this area by providing “a reasonable framework for clinical care and launch points for future research to refine and standardize optimal post-ESD surveillance strategies.”

Foremost, Dr. Wang and colleagues suggested that post-ESD surveillance is necessary because of a lack of standardization concerning the definition of complete resection, along with variable standards of pathological assessment in Western countries, compared with Japan, where pathologists use 2-3 mm serial sectioning and special stains to detect lymphovascular invasion, “which is essential to accurate histopathologic diagnosis and determination of curative resection.”

According to the authors, surveillance endoscopy should be performed with a high-definition endoscope augmented with dye-based or electronic chromoendoscopy, and ideally with optimal magnification.

“Although no supporting data are available at this time, it is prudent and may be reasonable to obtain central and peripheral biopsies of the post-ESD scar,” the authors wrote, noting that relevant mucosa should be checked for metachronous lesions.
 

Esophageal dysplasia and esophageal squamous cell carcinoma

Following curative resection of low-grade or high-grade esophageal squamous dysplasia, the authors suggested follow-up esophagogastroduodenoscopy (EGD) initially at intervals of 6-12 months, while advising against endoscopic ultrasonography and radiographic surveillance.

In contrast, Dr. Wang and colleagues suggested that superficial esophageal squamous cell carcinoma removed by ESD may benefit from a shorter interval of endoscopic surveillance, with a range of 3-6 months for first and second follow-up EGDs. Clinicians may also consider endoscopic ultrasonography with each EGD, plus an annual CT scan of the abdomen and chest, for 3-5 years.

“A limitation of ESD is that the at-risk esophagus is left in place, and there is a possibility of developing local recurrence or metachronous neoplasia,” the authors wrote. “Although local recurrence after ESD deemed pathologically curative of esophageal squamous cell carcinoma is infrequent, the development of metachronous lesions is not.”
 

Barrett’s dysplasia and esophageal adenocarcinoma

For all patients, curative removal of Barrett’s dysplasia or esophageal adenocarcinoma should be followed by endoscopy with mucosal ablative therapy at 2-3 months, with treatments every 2-3 months until complete eradication of intestinal metaplasia is achieved, according to Dr. Wang and colleagues.

After complete eradication, patients should be endoscopically screened from 3-12 months, depending on the degree of dysplasia or T-stage of adenocarcinoma, followed by screening procedures ranging from 6 months to 3 years, again depending on disease type.

“Endoscopic resection of visible Barrett’s neoplasia without treatment of Barrett’s esophagus has been associated with significant recurrence rates, so the objective of treatment should be endoscopic resection of visible or nodular dysplasia, followed by complete ablation of any remaining Barrett’s esophagus and associated (flat and/or invisible) dysplasia,” the authors wrote.
 

Gastric dysplasia and gastric adenocarcinoma

According to the update, after curative resection of gastric dysplasia, first follow-up endoscopy should be conducted at 6-12 months. Second follow-up should be conducted at 12 months for low-grade dysplasia versus 6-12 months for high-grade dysplasia, with annual exams thereafter.

For T1a early gastric cancer, the first two follow-up endoscopies should be performed at 6-month intervals, followed by annual exams. T1b Sm1 disease should be screened more aggressively, with 3-6 months intervals for first and second follow-up EGDs, plus CT scans of the abdomen and chest and/or endoscopic ultrasound every 6-12 months for 3-5 years.

“For lesions where a curative resection was achieved based on clinical criteria and histopathologic examination, surveillance is performed primarily to detect metachronous gastric cancers,” the authors wrote.
 

Colonic dysplasia and adenocarcinoma

According to the authors, adenomas with low-grade dysplasia or serrated sessile lesions without dysplasia removed by ESD should be rechecked by colonoscopy at 1 year and then 3 years, followed by adherence to U.S. Multi-Society Task Force recommendations.

For traditional serrated adenomas, serrated sessile lesions with dysplasia, adenomas with high-grade dysplasia, carcinoma in situ, intramucosal carcinoma, or dysplasia in the setting of inflammatory bowel disease, first follow-up colonoscopy should be conducted at 6-12 months, 1 year later, then 3 years after that, followed by reversion to USMSTF recommendations, although patients with IBD may benefit from annual colonoscopy.

Finally, patients with superficial T1 colonic adenocarcinoma should be screened more frequently, with colonoscopies at 3-6 months, 6 months, and 1 year, followed by adherence to USMSTF recommendations.

“The current Japanese guideline suggests that recurrence or metastasis after endoscopic resection of T1 (Sm) colonic carcinomas occurs mainly within 3-5 years,” the authors noted.
 

Rectal dysplasia and adenocarcinoma

Best practice advice suggestions for rectal dysplasia and adenocarcinoma are grouped similarly to the above advice for colonic lesions.

For lower-grade lesions, first follow-up with flexible sigmoidoscopy is suggested after 1 year, then 3 years, followed by reversion to USMSTF recommendations. Higher-grade dysplastic lesions should be checked after 6-12 months, 1 year, then 3 years, followed by adherence to USMSTF guidance, again excluding patients with IBD, who may benefit from annual exams.

Patients with superficial T1 rectal adenocarcinoma removed by ESD deemed pathologically curative should be checked with flexible sigmoidoscopy at 3-6 months, again at 3-6 months after first sigmoidoscopy, then every 6 months for a total of 5 years from the time of ESD, followed by adherence to USMSTF recommendations. At 1 year following ESD, patients should undergo colonoscopy, which can take the place of one of the follow-up flexible sigmoidoscopy exams; if an advanced adenoma is found, colonoscopy should be repeated after 1 year, versus 3 years if no advanced adenomas are found, followed by adherence to USMSTF recommendations. Patients with superficial T1 rectal adenocarcinoma should also undergo endoscopic ultrasound or pelvic MRI with contrast every 3-6 months for 2 years, followed by intervals of 6 months for a total of 5 years. Annual CT of the chest and abdomen may also be considered for a duration of 3-5 years.

Call for research

Dr. Wang and colleagues concluded their update with a call for research.

“We acknowledge that the level of evidence currently available to support much of our surveillance advice is generally low,” they wrote. “The intent of this clinical practice update was to propose surveillance strategies after potentially curative ESD for various GI neoplasms, which might also serve as reference points to stimulate research that will refine future clinical best practice advice.”

The article was supported by the AGA. The authors disclosed relationships with MicroTech, Olympus, Lumendi, U.S. Endoscopy, Boston Scientific, Steris and others.

This article was updated Dec. 15, 2021.

The American Gastroenterological Association recently published a Clinical Practice Update Commentary outlining surveillance strategies following endoscopic submucosal dissection (ESD) of dysplasia and early gastrointestinal cancer considered pathologically curative.

The suggested practice advice, which was put together by Andrew Y. Wang, MD, of the University of Virginia, Charlottesville, and colleagues, offers timelines and modalities of surveillance based on neoplasia type and location, with accompanying summaries of relevant literature.

“Long-term U.S. data about ESD outcomes for early GI neoplasia are only beginning to emerge,” the authors wrote in Gastroenterology. “As such, the current clinical practice regarding endoscopic surveillance intervals and the need for other testing (such as radiographic imaging) after ESD considered curative by histopathology is extrapolated from data derived from Asia and other countries, from concepts learned from polypectomy and piecemeal endoscopic mucosal resection (EMR), and from guideline recommendations after local surgical resection.”

The authors went on to suggest that current recommendations for post-ESD surveillance, including international guidelines “are based more so on expert opinion than rigorous evidence.”

The present update was written to offer additional clarity in this area by providing “a reasonable framework for clinical care and launch points for future research to refine and standardize optimal post-ESD surveillance strategies.”

Foremost, Dr. Wang and colleagues suggested that post-ESD surveillance is necessary because of a lack of standardization concerning the definition of complete resection, along with variable standards of pathological assessment in Western countries, compared with Japan, where pathologists use 2-3 mm serial sectioning and special stains to detect lymphovascular invasion, “which is essential to accurate histopathologic diagnosis and determination of curative resection.”

According to the authors, surveillance endoscopy should be performed with a high-definition endoscope augmented with dye-based or electronic chromoendoscopy, and ideally with optimal magnification.

“Although no supporting data are available at this time, it is prudent and may be reasonable to obtain central and peripheral biopsies of the post-ESD scar,” the authors wrote, noting that relevant mucosa should be checked for metachronous lesions.
 

Esophageal dysplasia and esophageal squamous cell carcinoma

Following curative resection of low-grade or high-grade esophageal squamous dysplasia, the authors suggested follow-up esophagogastroduodenoscopy (EGD) initially at intervals of 6-12 months, while advising against endoscopic ultrasonography and radiographic surveillance.

In contrast, Dr. Wang and colleagues suggested that superficial esophageal squamous cell carcinoma removed by ESD may benefit from a shorter interval of endoscopic surveillance, with a range of 3-6 months for first and second follow-up EGDs. Clinicians may also consider endoscopic ultrasonography with each EGD, plus an annual CT scan of the abdomen and chest, for 3-5 years.

“A limitation of ESD is that the at-risk esophagus is left in place, and there is a possibility of developing local recurrence or metachronous neoplasia,” the authors wrote. “Although local recurrence after ESD deemed pathologically curative of esophageal squamous cell carcinoma is infrequent, the development of metachronous lesions is not.”
 

Barrett’s dysplasia and esophageal adenocarcinoma

For all patients, curative removal of Barrett’s dysplasia or esophageal adenocarcinoma should be followed by endoscopy with mucosal ablative therapy at 2-3 months, with treatments every 2-3 months until complete eradication of intestinal metaplasia is achieved, according to Dr. Wang and colleagues.

After complete eradication, patients should be endoscopically screened from 3-12 months, depending on the degree of dysplasia or T-stage of adenocarcinoma, followed by screening procedures ranging from 6 months to 3 years, again depending on disease type.

“Endoscopic resection of visible Barrett’s neoplasia without treatment of Barrett’s esophagus has been associated with significant recurrence rates, so the objective of treatment should be endoscopic resection of visible or nodular dysplasia, followed by complete ablation of any remaining Barrett’s esophagus and associated (flat and/or invisible) dysplasia,” the authors wrote.
 

Gastric dysplasia and gastric adenocarcinoma

According to the update, after curative resection of gastric dysplasia, first follow-up endoscopy should be conducted at 6-12 months. Second follow-up should be conducted at 12 months for low-grade dysplasia versus 6-12 months for high-grade dysplasia, with annual exams thereafter.

For T1a early gastric cancer, the first two follow-up endoscopies should be performed at 6-month intervals, followed by annual exams. T1b Sm1 disease should be screened more aggressively, with 3-6 months intervals for first and second follow-up EGDs, plus CT scans of the abdomen and chest and/or endoscopic ultrasound every 6-12 months for 3-5 years.

“For lesions where a curative resection was achieved based on clinical criteria and histopathologic examination, surveillance is performed primarily to detect metachronous gastric cancers,” the authors wrote.
 

Colonic dysplasia and adenocarcinoma

According to the authors, adenomas with low-grade dysplasia or serrated sessile lesions without dysplasia removed by ESD should be rechecked by colonoscopy at 1 year and then 3 years, followed by adherence to U.S. Multi-Society Task Force recommendations.

For traditional serrated adenomas, serrated sessile lesions with dysplasia, adenomas with high-grade dysplasia, carcinoma in situ, intramucosal carcinoma, or dysplasia in the setting of inflammatory bowel disease, first follow-up colonoscopy should be conducted at 6-12 months, 1 year later, then 3 years after that, followed by reversion to USMSTF recommendations, although patients with IBD may benefit from annual colonoscopy.

Finally, patients with superficial T1 colonic adenocarcinoma should be screened more frequently, with colonoscopies at 3-6 months, 6 months, and 1 year, followed by adherence to USMSTF recommendations.

“The current Japanese guideline suggests that recurrence or metastasis after endoscopic resection of T1 (Sm) colonic carcinomas occurs mainly within 3-5 years,” the authors noted.
 

Rectal dysplasia and adenocarcinoma

Best practice advice suggestions for rectal dysplasia and adenocarcinoma are grouped similarly to the above advice for colonic lesions.

For lower-grade lesions, first follow-up with flexible sigmoidoscopy is suggested after 1 year, then 3 years, followed by reversion to USMSTF recommendations. Higher-grade dysplastic lesions should be checked after 6-12 months, 1 year, then 3 years, followed by adherence to USMSTF guidance, again excluding patients with IBD, who may benefit from annual exams.

Patients with superficial T1 rectal adenocarcinoma removed by ESD deemed pathologically curative should be checked with flexible sigmoidoscopy at 3-6 months, again at 3-6 months after first sigmoidoscopy, then every 6 months for a total of 5 years from the time of ESD, followed by adherence to USMSTF recommendations. At 1 year following ESD, patients should undergo colonoscopy, which can take the place of one of the follow-up flexible sigmoidoscopy exams; if an advanced adenoma is found, colonoscopy should be repeated after 1 year, versus 3 years if no advanced adenomas are found, followed by adherence to USMSTF recommendations. Patients with superficial T1 rectal adenocarcinoma should also undergo endoscopic ultrasound or pelvic MRI with contrast every 3-6 months for 2 years, followed by intervals of 6 months for a total of 5 years. Annual CT of the chest and abdomen may also be considered for a duration of 3-5 years.

Call for research

Dr. Wang and colleagues concluded their update with a call for research.

“We acknowledge that the level of evidence currently available to support much of our surveillance advice is generally low,” they wrote. “The intent of this clinical practice update was to propose surveillance strategies after potentially curative ESD for various GI neoplasms, which might also serve as reference points to stimulate research that will refine future clinical best practice advice.”

The article was supported by the AGA. The authors disclosed relationships with MicroTech, Olympus, Lumendi, U.S. Endoscopy, Boston Scientific, Steris and others.

This article was updated Dec. 15, 2021.

LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.

Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.

“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”

To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.

After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.

CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.

Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.

“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”

Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.

“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”

Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.

“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”

The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.

“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”

The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.

LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.

Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.

“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”

To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.

After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.

CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.

Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.

“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”

Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.

“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”

Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.

“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”

The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.

“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”

The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.

LAS VEGAS – Although endoscopic resection of T1 esophageal adenocarcinoma (EAC) is associated with excellent overall survival, recurrence can occur years later, emphasizing the need for long-term surveillance, according to investigators.

Recurrence was about twice as common among patients lacking complete remission of intestinal metaplasia (CRIM) upon follow-up, reported lead author Kevin Song, MD, of the Mayo Clinic, Scottsdale, Ariz., and colleagues.

“Endoscopic resection of early-stage EAC has gained acceptance in recent years,” Dr. Song said during his presentation at the annual meeting of the American College of Gastroenterology. “While studies have demonstrated promising outcomes for short-term remission and recurrence, little is known about long-term recurrence and EAC-related mortality beyond 5 years.”

To address this knowledge gap, Dr. Song and colleagues reviewed data from 98 patients who had undergone endoscopic resection of T1 EAC at four tertiary academic centers with follow-up of at least 5 years. CRIM was defined by negative biopsies from the tubular esophagus and the gastroesophageal junction at one posttreatment surveillance endoscopy. Early recurrence was defined by a 2-year limit.

After a median follow-up of 8.76 years, 93 out of 98 patients (95%) experienced remission, while 82 patients (84%) demonstrated CRIM. Fourteen patients (14%) had recurrence of EAC, among whom eight (57%) had early recurrence at a median of 0.75 years (interquartile range, 0.43-0.80 years), while the other six (43%) had late recurrence at a median of 7.7 years (IQR, 5.20-8.77 years). Among the 93 patients entering remission, five (5.38%) had recurrence after 5 years.

CRIM was associated with a significantly lower rate of recurrence (11% vs. 46%; P = .01), generating an odds ratio of 6.55 (95% confidence interval, 1.71-26.71). Patients with CRIM also had later recurrence, at a median of 5.20 years, compared with 0.81 years for patients without CRIM. Moreover, the overall EAC-related mortality rate was 6.45%.

Dr. Song noted excellent overall survival and concluded his presentation by emphasizing the predictive value of CRIM and the need for long-term surveillance.

“CRIM should be considered the most significant endpoint for endotherapy of T1 EAC,” he said. “Surveillance is important even when early recurrence is not observed.”

Rishindra M. Reddy, MD, professor of thoracic surgery at the University of Michigan Health, Ann Arbor, agreed “100%” with Dr. Song and colleagues’ conclusion about the need for long-term surveillance.

“We struggle, in our patient population, to get people to do regular surveillance,” he said. “I think you have to have patients who have regular access to their gastroenterologist or surgeons and are willing to come in every 3 months to 6 months for surveillance endoscopies as well as CT scans.”

Dr. Reddy recommended that endoscopic resection of EAC be handled at high-volume centers.

“This really needs to be done in a multidisciplinary setting where you have both experienced endoscopists and thoracic surgeons and/or surgical oncologists who do esophagectomies to make these decisions about optimal treatment,” he said, “as well as pathologists who are more experienced in what to look for in terms of depth or lateral margins.”

The present work is a “great first study,” Dr. Reddy said. He suggested that larger real-world trials are needed to confirm findings and compare outcomes between tumor subtypes.

“I think for T1a tumors, there’s a good consensus on endoscopic mucosal resection,” he said. “I think T1b is an area where we would suggest more often doing surgery… and there’s even some nuance at a T1a level about the depth. It would be helpful to understand the risks of recurrence after [resecting] different levels of T1 tumors.”

The investigators disclosed relationships with CDX, Interpace, Lucid, and others. Dr. Reddy disclosed no relevant conflicts of interest.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

Erenumab, a calcitonin-gene related peptide receptor (CGRP) inhibitor, is more tolerable and effective than topiramate for treating patients with migraine, according to data from almost 800 patients in the first head-to-head trial of its kind.

The findings suggest that erenumab may help overcome longstanding issues with migraine medication adherence, and additional supportive data may alter treatment sequencing, reported lead author Uwe Reuter, MD, professor at Charité Universitätsmedizin Berlin, and colleagues.

“So far, no study has been done in order to compare the efficacy of a monoclonal antibody targeting the CGRP pathway to that of a standard of care oral preventive drug,” the investigators wrote in Cephalalgia.

The phase 4 HER-MES trial aimed to address this knowledge gap by enrolling 777 adult patients with a history of migraine. All patients reported migraine with or without aura for at least 1 year prior to screening. At baseline, most patients (65%) reported 8-14 migraine days per months, followed by 4-7 days (24.0%), and at least 15 days (11.0%). No patients had previously received topiramate or a CGRP-targeting agent.

“HER-MES includes a broad migraine population with two-thirds of the patients in the high-frequency migraine spectrum,” the investigators noted. “Despite a mean disease duration of about 20 years, almost 60% of the patients had not received previous prophylactic treatment, which underlines the long-standing problem of undertreatment in migraine.”

The trial had a double-dummy design; patients were randomized in a 1:1 ratio to receive either subcutaneous erenumab (70 or 140 mg/month) plus oral placebo, or oral topiramate (50-100 mg/day) plus subcutaneous placebo. The topiramate dose was uptitrated over the first 6 weeks. Treatments were given for a total of 24 weeks or until discontinuation due to adverse events, which was the primary endpoint. The secondary endpoint was efficacy over months 4-6, defined as at least 50% reduction in monthly migraine days, compared with baseline. Other patient-reported outcomes were also evaluated.

After 24 weeks, 95.1% of patients were still enrolled in the trial. Discontinuations due to adverse events were almost four times as common in the topiramate group than the erenumab group (38.9% vs. 10.6%; odds ratio [OR], 0.19; confidence interval, 0.13-0.27; P less than .001). Efficacy findings followed suit, with 55.4% of patients in the erenumab group reporting at least 50% reduction in monthly migraine days, compared with 31.2% of patients in the topiramate group (OR, 2.76; 95% CI, 2.06-3.71; P less than.001).

Erenumab significantly improved monthly migraine days, headache impact test (HIT-6) scores, and short form health survey version (SF-35v2) scores, including physical and mental components (P less than .001 for all).

Safety profiles aligned with previous findings.

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy,” the investigators concluded. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden, and improving quality of life in a broad migraine population.”
 

Superior tolerability

Commenting on the study, Alan Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, and editor-in-chief of Neurology Reviews, said this is “a very important, very well conducted trial that documents what many of us already suspected; erenumab clearly has better tolerability than topiramate as well as better efficacy.”

Dr. Rapoport, a past president of the International Headache Society, said the study highlights an area of unmet need in neurology practice.

“Despite most patients in the trial having chronic headaches for 20 years, 60% of them had never received preventive treatment,” he said, noting that this reflects current practice in the United States.

Dr. Rapoport said primary care providers in the United States prescribe preventive migraine medications to 10%-15% of eligible patients. Prescribing rates for general neurologists are slightly higher, he said, ranging from 35% to 40%, while headache specialists prescribe 70%-90% of the time.

“How can we improve this situation?” Dr. Rapoport asked. “For years we have tried to improve it with education, but we need to do a better job. We need to educate our primary care physicians in more practical ways. We have to teach them how to make a diagnosis of high frequency migraine and chronic migraine and strongly suggest that those patients be put on appropriate preventive medications.”

Barriers to care may be systemic, according to Dr. Rapoport.

“One issue in the U.S. is that patients with commercial insurance are almost always required to fail two or three categories of older oral preventive migraine medications before they can get a monoclonal antibody or gepants for prevention,” he said. “It would be good if we could change that system so that patients that absolutely need the better tolerated, more effective preventive medications could get them sooner rather than later. This will help them feel and function better, with less pain, and eventually bring down the cost of migraine therapy.”

While Dr. Reuter and colleagues concluded that revised treatment sequencing may be warranted after more trials show similar results, Dr. Rapoport suggested that “this was such a large, well-performed, 6-month study with few dropouts, that further trials to confirm these findings are unnecessary, in my opinion.”

The HER-MES trial was funded by Novartis. Dr. Reuter and colleagues disclosed additional relationships with Eli Lilly, Teva Pharmaceutical, Allergan, and others. Dr. Rapoport was involved in early topiramate trials for prevention and migraine, and is a speaker for Amgen.

The oral sphingosine-1-phosphate receptor modulator ozanimod is significantly more effective than placebo for treating patients with moderate to severe ulcerative colitis, regardless of prior biologic exposure, based on results of the phase 3 True North trial.

Courtesy Icahn School of Medicine at Mount Sinai

Although improvements were seen across all patients, those who had previously used biologics took slightly longer to respond to treatment, which suggests that any initial improvements with ozanimod warrant continuation of therapy to achieve full effect, reported to lead author Bruce E. Sands, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

“[Ulcerative colitis] patients previously treated with a biologic agent may be less likely to respond to another advanced treatment,” Dr. Sands said during a presentation at the annual meeting of the American College of Gastroenterology.

Dr. Sands and colleagues evaluated this possibility in the True North trial, which previously demonstrated superior efficacy and safety of ozanimod over placebo through 1 year.

The present dataset included a double-blinded cohort of 639 patients (cohort 1), among whom 213 took placebo and 426 took ozanimod, and an open-label cohort of 353 patients who took ozanimod (cohort 2). Outcomes included clinical remission, clinical response, endoscopic improvement, and mucosal healing.

During induction (through week 10), biologic-naive patients in both cohorts generally responded better to ozanimod than those who had received at least one prior biologic. Patients who had received two or more biologics showed less improvement than those who had received only one prior biologic.

For example, in cohort 1, 53% of biologic-naive patients in the ozanimod group achieved a clinical response, compared with 50% of patients who had received one prior biologic, and just 27.2% of patients who had received two or more biologics.

With maintenance therapy, however, these differences faded. Among participants continuing ozanimod through week 52, 60.7% of biologic-naive patients achieved a clinical response, compared with 60.5% of those who had taken one prior biologic, and 55.3% of patients who had taken two or more prior biologics.

“Ozanimod treatment for up to 52 weeks in patients with moderate to severe ulcerative colitis improved clinical symptoms, mucosal ulcerations, and reduced cellular inflammation in both biologic-exposed and biologic-naive patients,” Dr. Sands concluded. “Greater efficacy was observed in biologic-naive patients, followed by patients with prior exposure to one biologic, at induction; however, all groups had benefits at end of maintenance. Patients with prior biologic use may require additional time to respond to treatment.”

Bradley Morganstern, MD, codirector of the IBD Center at Stony Brook (N.Y.) Medicine, called the study “a really important analysis” that addresses a common clinical decision.

“We often see a lower response rate among patients previously on biologics, but we have very limited data to guide us on how to choose a second-line agent,” Dr. Morganstern said during an interview.

He said the current findings encourage use of ozanimod for patients who didn’t respond to other biologics.

“The takeaway is that just because someone didn’t respond to a biologic in the past doesn’t mean they won’t respond to this,” Dr. Morganstern said. “They actually have a very good chance of responding – similar to the rest of the population that was never on medication.”

He went on to explain that exact treatment sequencing remains unclear, although ozanimod is a strong candidate in the second line.

“We can’t 100% say where it [ozanimod] fits in,” Dr. Morganstern said, “but we should certainly place it high up in the algorithm for patients who have failed a biologic. This should strongly be considered as a second-line agent.”

Dr. Morganstern said that he looks forward to long-term findings from True North beyond 1 year, “in terms of maintaining response,” and additional safety data.

The study was funded supported by Bristol-Myers Squibb. The investigators disclosed additional affiliations with AstraZeneca, AbbVie, Amgen, and others. Dr. Morganstern has previously spoken for Bristol-Myers Squibb.

The oral sphingosine-1-phosphate receptor modulator ozanimod is significantly more effective than placebo for treating patients with moderate to severe ulcerative colitis, regardless of prior biologic exposure, based on results of the phase 3 True North trial.

Courtesy Icahn School of Medicine at Mount Sinai

Although improvements were seen across all patients, those who had previously used biologics took slightly longer to respond to treatment, which suggests that any initial improvements with ozanimod warrant continuation of therapy to achieve full effect, reported to lead author Bruce E. Sands, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

“[Ulcerative colitis] patients previously treated with a biologic agent may be less likely to respond to another advanced treatment,” Dr. Sands said during a presentation at the annual meeting of the American College of Gastroenterology.

Dr. Sands and colleagues evaluated this possibility in the True North trial, which previously demonstrated superior efficacy and safety of ozanimod over placebo through 1 year.

The present dataset included a double-blinded cohort of 639 patients (cohort 1), among whom 213 took placebo and 426 took ozanimod, and an open-label cohort of 353 patients who took ozanimod (cohort 2). Outcomes included clinical remission, clinical response, endoscopic improvement, and mucosal healing.

During induction (through week 10), biologic-naive patients in both cohorts generally responded better to ozanimod than those who had received at least one prior biologic. Patients who had received two or more biologics showed less improvement than those who had received only one prior biologic.

For example, in cohort 1, 53% of biologic-naive patients in the ozanimod group achieved a clinical response, compared with 50% of patients who had received one prior biologic, and just 27.2% of patients who had received two or more biologics.

With maintenance therapy, however, these differences faded. Among participants continuing ozanimod through week 52, 60.7% of biologic-naive patients achieved a clinical response, compared with 60.5% of those who had taken one prior biologic, and 55.3% of patients who had taken two or more prior biologics.

“Ozanimod treatment for up to 52 weeks in patients with moderate to severe ulcerative colitis improved clinical symptoms, mucosal ulcerations, and reduced cellular inflammation in both biologic-exposed and biologic-naive patients,” Dr. Sands concluded. “Greater efficacy was observed in biologic-naive patients, followed by patients with prior exposure to one biologic, at induction; however, all groups had benefits at end of maintenance. Patients with prior biologic use may require additional time to respond to treatment.”

Bradley Morganstern, MD, codirector of the IBD Center at Stony Brook (N.Y.) Medicine, called the study “a really important analysis” that addresses a common clinical decision.

“We often see a lower response rate among patients previously on biologics, but we have very limited data to guide us on how to choose a second-line agent,” Dr. Morganstern said during an interview.

He said the current findings encourage use of ozanimod for patients who didn’t respond to other biologics.

“The takeaway is that just because someone didn’t respond to a biologic in the past doesn’t mean they won’t respond to this,” Dr. Morganstern said. “They actually have a very good chance of responding – similar to the rest of the population that was never on medication.”

He went on to explain that exact treatment sequencing remains unclear, although ozanimod is a strong candidate in the second line.

“We can’t 100% say where it [ozanimod] fits in,” Dr. Morganstern said, “but we should certainly place it high up in the algorithm for patients who have failed a biologic. This should strongly be considered as a second-line agent.”

Dr. Morganstern said that he looks forward to long-term findings from True North beyond 1 year, “in terms of maintaining response,” and additional safety data.

The study was funded supported by Bristol-Myers Squibb. The investigators disclosed additional affiliations with AstraZeneca, AbbVie, Amgen, and others. Dr. Morganstern has previously spoken for Bristol-Myers Squibb.

The oral sphingosine-1-phosphate receptor modulator ozanimod is significantly more effective than placebo for treating patients with moderate to severe ulcerative colitis, regardless of prior biologic exposure, based on results of the phase 3 True North trial.

Courtesy Icahn School of Medicine at Mount Sinai

Although improvements were seen across all patients, those who had previously used biologics took slightly longer to respond to treatment, which suggests that any initial improvements with ozanimod warrant continuation of therapy to achieve full effect, reported to lead author Bruce E. Sands, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

“[Ulcerative colitis] patients previously treated with a biologic agent may be less likely to respond to another advanced treatment,” Dr. Sands said during a presentation at the annual meeting of the American College of Gastroenterology.

Dr. Sands and colleagues evaluated this possibility in the True North trial, which previously demonstrated superior efficacy and safety of ozanimod over placebo through 1 year.

The present dataset included a double-blinded cohort of 639 patients (cohort 1), among whom 213 took placebo and 426 took ozanimod, and an open-label cohort of 353 patients who took ozanimod (cohort 2). Outcomes included clinical remission, clinical response, endoscopic improvement, and mucosal healing.

During induction (through week 10), biologic-naive patients in both cohorts generally responded better to ozanimod than those who had received at least one prior biologic. Patients who had received two or more biologics showed less improvement than those who had received only one prior biologic.

For example, in cohort 1, 53% of biologic-naive patients in the ozanimod group achieved a clinical response, compared with 50% of patients who had received one prior biologic, and just 27.2% of patients who had received two or more biologics.

With maintenance therapy, however, these differences faded. Among participants continuing ozanimod through week 52, 60.7% of biologic-naive patients achieved a clinical response, compared with 60.5% of those who had taken one prior biologic, and 55.3% of patients who had taken two or more prior biologics.

“Ozanimod treatment for up to 52 weeks in patients with moderate to severe ulcerative colitis improved clinical symptoms, mucosal ulcerations, and reduced cellular inflammation in both biologic-exposed and biologic-naive patients,” Dr. Sands concluded. “Greater efficacy was observed in biologic-naive patients, followed by patients with prior exposure to one biologic, at induction; however, all groups had benefits at end of maintenance. Patients with prior biologic use may require additional time to respond to treatment.”

Bradley Morganstern, MD, codirector of the IBD Center at Stony Brook (N.Y.) Medicine, called the study “a really important analysis” that addresses a common clinical decision.

“We often see a lower response rate among patients previously on biologics, but we have very limited data to guide us on how to choose a second-line agent,” Dr. Morganstern said during an interview.

He said the current findings encourage use of ozanimod for patients who didn’t respond to other biologics.

“The takeaway is that just because someone didn’t respond to a biologic in the past doesn’t mean they won’t respond to this,” Dr. Morganstern said. “They actually have a very good chance of responding – similar to the rest of the population that was never on medication.”

He went on to explain that exact treatment sequencing remains unclear, although ozanimod is a strong candidate in the second line.

“We can’t 100% say where it [ozanimod] fits in,” Dr. Morganstern said, “but we should certainly place it high up in the algorithm for patients who have failed a biologic. This should strongly be considered as a second-line agent.”

Dr. Morganstern said that he looks forward to long-term findings from True North beyond 1 year, “in terms of maintaining response,” and additional safety data.

The study was funded supported by Bristol-Myers Squibb. The investigators disclosed additional affiliations with AstraZeneca, AbbVie, Amgen, and others. Dr. Morganstern has previously spoken for Bristol-Myers Squibb.

Induction therapy with Janus kinase inhibitor upadacitinib is superior to placebo for patients with moderately to severely active ulcerative colitis (UC), regardless of prior biologic treatments, based on results of the phase 3 U-ACHIEVE trial.

Clinical responses in the upadacitinib group occurred as soon as 2 weeks and were sustained through the 8-week study period, reported lead author Silvio Danese, MD, PhD, of Humanitas Clinical and Research Center IRCCS and Hunimed, Milan.

“Despite availability of multiple treatment options, many patients with ulcerative colitis do not achieve disease remission with current therapies and unmet therapeutic need remains, especially in patients with moderate to severe disease,” said coauthor Peter Higgins, MD, PhD, of the University of Michigan, Ann Arbor, who presented findings at the annual meeting of the American College of Gastroenterology.

The U-ACHIEVE trial involved 474 patients with moderate to severe UC randomized to receive either upadacitinib induction therapy (45 mg once daily; n = 319) or placebo (n = 155). The primary endpoint was clinical remission at week 8. Secondary endpoints included endoscopic improvement at week 8, endoscopic remission at week 8, clinical response at week 8, clinical response at week 2, histologic-endoscopic mucosal improvement at week 8, and adverse events.

The study population was “very sick” and “very experienced,” Dr. Higgins said, noting that approximately half of the patients had inadequate responses to prior biologics, and within this subgroup of inadequate responders, approximately two-thirds of the patients had received more than one prior biologic. According to Dr. Higgins, this helps explain why 12.3% of the patients in the placebo group discontinued therapy, compared with just 3.8% in the upadacitinib group – because most patients involved were “quite ill.”

At week 8, 26.1% of the patients in the upadacitinib group had achieved clinical remission, versus 4.8% of the patients given placebo (26.1% vs. 4.8%; P < .0001). Clinical response at week 2 followed a similar pattern (60.1% vs. 27.3%; P < .001), as did clinical response at week 8 (72.6% vs. 27.3%; P < .0001).

All other 8-week secondary endpoints also significantly favored upadacitinib, including endoscopic improvement (36.3% vs 7.4%), endoscopic remission (13.7% vs 1.3%), and histologic-endoscopic mucosal improvement (29.9% vs. 6.5%).

Serious and severe adverse events were more common in the placebo group, and patients in the placebo group more frequently discontinued therapy because of treatment-related adverse events. While rates of serious infection were similar between groups, patients taking upadacitinib had higher rates of neutropenia and lymphopenia.

Based on these findings, the investigators concluded that upadacitinib induction therapy is superior to placebo for clinical remission and clinical response regardless of previous treatment failure.

According to Jordan E. Axelrad, MD, of New York University Langone Health, the findings reflect a real-world setting and clinicians should take note of the rapid response observed with upadacitinib.

“This was a relatively sick group, so you know this reflects what we’re seeing in clinical practice,” Dr. Axelrad said in an interview. “Clinical response was detected as early week 2, and that’s extremely important to highlight, because a lot of our drugs that we have on the market – some of these biologics – may take a little time to work. Having a drug that can work fast and is effective is critical.”

Dr. Axelrad suggested that second-line JAK inhibitors like upadacitinib, which target JAK proteins more selectively than first-generation agents, may alleviate some lingering concerns about JAK inhibitor safety; still, optimal treatment sequencing remains unclear.

“With more selective inhibition, you’re getting less of that side-effect profile,” Dr. Axelrad said, noting that long-term data is needed to confirm this likelihood. “The real question moving forward is: Will upadacitinib replace first-generation JAK inhibitors as a category, or, because of the broader safety profile, will it come earlier in the positioning of where we put our drugs for colitis?”

Dr. Axelrad suggested that the answer may ultimately come from regulators, although patients could also guide decision-making.

“Oral drugs are a really important mode of administration that we’re missing for the moderate to severe group,” he said. “Should [further clinical trials] demonstrate superior safety to nonselective JAK inhibitors, upadacitinib could be a first-line option for patients who don’t want to be taking an infusion or injection, more especially so for those that are already biologically experienced, or need something fast.”

Siddharth Singh, MD, director of the IBD Center at the University of California, San Diego, called U-ACHIEVE a “pivotal trial” that demonstrated the “remarkable efficacy” of upadacitinib for moderate to severe ulcerative colitis; still, he noted that drug sequencing remains undetermined.

“It’s unclear whether or not it’ll be the best in class for JAK inhibitors right now,” Dr. Singh said in an interview. “A lot of that hinges on the safety of this drug. In terms of positioning, it depends on whether the [Food and Drug Administration] requires patients to have failed anti–[tumor necrosis factor] therapy before using this drug, like tofacitinib.”

That may depend on long-term data, he suggested.

“Right now, it is hard to comment on the relative safety of upadacitinib versus tofacitinib,” Dr. Singh said. “While the JAK1 selectivity may contribute to efficacy by allowing us to use a higher dose, it’s unclear whether the higher dose of this medication is any safer than tofacitinib. Longer term, 5- to 7-year registry studies of real-world data are warranted to examine risk of cardiovascular disease, thromboembolism, malignancy, and mortality with upadacitinib.

“How to sequence and position these therapies in real-world practice is a key question,” he concluded.

The study was supported by AbbVie. The investigators disclosed additional affiliations with Genentech, Ferring, AstraZeneca, and others. Dr. Axelrad has previously consulted for AbbVie. Dr. Singh has received research funding from AbbVie, Pfizer, and Janssen in the last 24 months, as well as personal fees from Pfizer for an ad hoc grant review.

Induction therapy with Janus kinase inhibitor upadacitinib is superior to placebo for patients with moderately to severely active ulcerative colitis (UC), regardless of prior biologic treatments, based on results of the phase 3 U-ACHIEVE trial.

Clinical responses in the upadacitinib group occurred as soon as 2 weeks and were sustained through the 8-week study period, reported lead author Silvio Danese, MD, PhD, of Humanitas Clinical and Research Center IRCCS and Hunimed, Milan.

“Despite availability of multiple treatment options, many patients with ulcerative colitis do not achieve disease remission with current therapies and unmet therapeutic need remains, especially in patients with moderate to severe disease,” said coauthor Peter Higgins, MD, PhD, of the University of Michigan, Ann Arbor, who presented findings at the annual meeting of the American College of Gastroenterology.

The U-ACHIEVE trial involved 474 patients with moderate to severe UC randomized to receive either upadacitinib induction therapy (45 mg once daily; n = 319) or placebo (n = 155). The primary endpoint was clinical remission at week 8. Secondary endpoints included endoscopic improvement at week 8, endoscopic remission at week 8, clinical response at week 8, clinical response at week 2, histologic-endoscopic mucosal improvement at week 8, and adverse events.

The study population was “very sick” and “very experienced,” Dr. Higgins said, noting that approximately half of the patients had inadequate responses to prior biologics, and within this subgroup of inadequate responders, approximately two-thirds of the patients had received more than one prior biologic. According to Dr. Higgins, this helps explain why 12.3% of the patients in the placebo group discontinued therapy, compared with just 3.8% in the upadacitinib group – because most patients involved were “quite ill.”

At week 8, 26.1% of the patients in the upadacitinib group had achieved clinical remission, versus 4.8% of the patients given placebo (26.1% vs. 4.8%; P < .0001). Clinical response at week 2 followed a similar pattern (60.1% vs. 27.3%; P < .001), as did clinical response at week 8 (72.6% vs. 27.3%; P < .0001).

All other 8-week secondary endpoints also significantly favored upadacitinib, including endoscopic improvement (36.3% vs 7.4%), endoscopic remission (13.7% vs 1.3%), and histologic-endoscopic mucosal improvement (29.9% vs. 6.5%).

Serious and severe adverse events were more common in the placebo group, and patients in the placebo group more frequently discontinued therapy because of treatment-related adverse events. While rates of serious infection were similar between groups, patients taking upadacitinib had higher rates of neutropenia and lymphopenia.

Based on these findings, the investigators concluded that upadacitinib induction therapy is superior to placebo for clinical remission and clinical response regardless of previous treatment failure.

According to Jordan E. Axelrad, MD, of New York University Langone Health, the findings reflect a real-world setting and clinicians should take note of the rapid response observed with upadacitinib.

“This was a relatively sick group, so you know this reflects what we’re seeing in clinical practice,” Dr. Axelrad said in an interview. “Clinical response was detected as early week 2, and that’s extremely important to highlight, because a lot of our drugs that we have on the market – some of these biologics – may take a little time to work. Having a drug that can work fast and is effective is critical.”

Dr. Axelrad suggested that second-line JAK inhibitors like upadacitinib, which target JAK proteins more selectively than first-generation agents, may alleviate some lingering concerns about JAK inhibitor safety; still, optimal treatment sequencing remains unclear.

“With more selective inhibition, you’re getting less of that side-effect profile,” Dr. Axelrad said, noting that long-term data is needed to confirm this likelihood. “The real question moving forward is: Will upadacitinib replace first-generation JAK inhibitors as a category, or, because of the broader safety profile, will it come earlier in the positioning of where we put our drugs for colitis?”

Dr. Axelrad suggested that the answer may ultimately come from regulators, although patients could also guide decision-making.

“Oral drugs are a really important mode of administration that we’re missing for the moderate to severe group,” he said. “Should [further clinical trials] demonstrate superior safety to nonselective JAK inhibitors, upadacitinib could be a first-line option for patients who don’t want to be taking an infusion or injection, more especially so for those that are already biologically experienced, or need something fast.”

Siddharth Singh, MD, director of the IBD Center at the University of California, San Diego, called U-ACHIEVE a “pivotal trial” that demonstrated the “remarkable efficacy” of upadacitinib for moderate to severe ulcerative colitis; still, he noted that drug sequencing remains undetermined.

“It’s unclear whether or not it’ll be the best in class for JAK inhibitors right now,” Dr. Singh said in an interview. “A lot of that hinges on the safety of this drug. In terms of positioning, it depends on whether the [Food and Drug Administration] requires patients to have failed anti–[tumor necrosis factor] therapy before using this drug, like tofacitinib.”

That may depend on long-term data, he suggested.

“Right now, it is hard to comment on the relative safety of upadacitinib versus tofacitinib,” Dr. Singh said. “While the JAK1 selectivity may contribute to efficacy by allowing us to use a higher dose, it’s unclear whether the higher dose of this medication is any safer than tofacitinib. Longer term, 5- to 7-year registry studies of real-world data are warranted to examine risk of cardiovascular disease, thromboembolism, malignancy, and mortality with upadacitinib.

“How to sequence and position these therapies in real-world practice is a key question,” he concluded.

The study was supported by AbbVie. The investigators disclosed additional affiliations with Genentech, Ferring, AstraZeneca, and others. Dr. Axelrad has previously consulted for AbbVie. Dr. Singh has received research funding from AbbVie, Pfizer, and Janssen in the last 24 months, as well as personal fees from Pfizer for an ad hoc grant review.

Induction therapy with Janus kinase inhibitor upadacitinib is superior to placebo for patients with moderately to severely active ulcerative colitis (UC), regardless of prior biologic treatments, based on results of the phase 3 U-ACHIEVE trial.

Clinical responses in the upadacitinib group occurred as soon as 2 weeks and were sustained through the 8-week study period, reported lead author Silvio Danese, MD, PhD, of Humanitas Clinical and Research Center IRCCS and Hunimed, Milan.

“Despite availability of multiple treatment options, many patients with ulcerative colitis do not achieve disease remission with current therapies and unmet therapeutic need remains, especially in patients with moderate to severe disease,” said coauthor Peter Higgins, MD, PhD, of the University of Michigan, Ann Arbor, who presented findings at the annual meeting of the American College of Gastroenterology.

The U-ACHIEVE trial involved 474 patients with moderate to severe UC randomized to receive either upadacitinib induction therapy (45 mg once daily; n = 319) or placebo (n = 155). The primary endpoint was clinical remission at week 8. Secondary endpoints included endoscopic improvement at week 8, endoscopic remission at week 8, clinical response at week 8, clinical response at week 2, histologic-endoscopic mucosal improvement at week 8, and adverse events.

The study population was “very sick” and “very experienced,” Dr. Higgins said, noting that approximately half of the patients had inadequate responses to prior biologics, and within this subgroup of inadequate responders, approximately two-thirds of the patients had received more than one prior biologic. According to Dr. Higgins, this helps explain why 12.3% of the patients in the placebo group discontinued therapy, compared with just 3.8% in the upadacitinib group – because most patients involved were “quite ill.”

At week 8, 26.1% of the patients in the upadacitinib group had achieved clinical remission, versus 4.8% of the patients given placebo (26.1% vs. 4.8%; P < .0001). Clinical response at week 2 followed a similar pattern (60.1% vs. 27.3%; P < .001), as did clinical response at week 8 (72.6% vs. 27.3%; P < .0001).

All other 8-week secondary endpoints also significantly favored upadacitinib, including endoscopic improvement (36.3% vs 7.4%), endoscopic remission (13.7% vs 1.3%), and histologic-endoscopic mucosal improvement (29.9% vs. 6.5%).

Serious and severe adverse events were more common in the placebo group, and patients in the placebo group more frequently discontinued therapy because of treatment-related adverse events. While rates of serious infection were similar between groups, patients taking upadacitinib had higher rates of neutropenia and lymphopenia.

Based on these findings, the investigators concluded that upadacitinib induction therapy is superior to placebo for clinical remission and clinical response regardless of previous treatment failure.

According to Jordan E. Axelrad, MD, of New York University Langone Health, the findings reflect a real-world setting and clinicians should take note of the rapid response observed with upadacitinib.

“This was a relatively sick group, so you know this reflects what we’re seeing in clinical practice,” Dr. Axelrad said in an interview. “Clinical response was detected as early week 2, and that’s extremely important to highlight, because a lot of our drugs that we have on the market – some of these biologics – may take a little time to work. Having a drug that can work fast and is effective is critical.”

Dr. Axelrad suggested that second-line JAK inhibitors like upadacitinib, which target JAK proteins more selectively than first-generation agents, may alleviate some lingering concerns about JAK inhibitor safety; still, optimal treatment sequencing remains unclear.

“With more selective inhibition, you’re getting less of that side-effect profile,” Dr. Axelrad said, noting that long-term data is needed to confirm this likelihood. “The real question moving forward is: Will upadacitinib replace first-generation JAK inhibitors as a category, or, because of the broader safety profile, will it come earlier in the positioning of where we put our drugs for colitis?”

Dr. Axelrad suggested that the answer may ultimately come from regulators, although patients could also guide decision-making.

“Oral drugs are a really important mode of administration that we’re missing for the moderate to severe group,” he said. “Should [further clinical trials] demonstrate superior safety to nonselective JAK inhibitors, upadacitinib could be a first-line option for patients who don’t want to be taking an infusion or injection, more especially so for those that are already biologically experienced, or need something fast.”

Siddharth Singh, MD, director of the IBD Center at the University of California, San Diego, called U-ACHIEVE a “pivotal trial” that demonstrated the “remarkable efficacy” of upadacitinib for moderate to severe ulcerative colitis; still, he noted that drug sequencing remains undetermined.

“It’s unclear whether or not it’ll be the best in class for JAK inhibitors right now,” Dr. Singh said in an interview. “A lot of that hinges on the safety of this drug. In terms of positioning, it depends on whether the [Food and Drug Administration] requires patients to have failed anti–[tumor necrosis factor] therapy before using this drug, like tofacitinib.”

That may depend on long-term data, he suggested.

“Right now, it is hard to comment on the relative safety of upadacitinib versus tofacitinib,” Dr. Singh said. “While the JAK1 selectivity may contribute to efficacy by allowing us to use a higher dose, it’s unclear whether the higher dose of this medication is any safer than tofacitinib. Longer term, 5- to 7-year registry studies of real-world data are warranted to examine risk of cardiovascular disease, thromboembolism, malignancy, and mortality with upadacitinib.

“How to sequence and position these therapies in real-world practice is a key question,” he concluded.

The study was supported by AbbVie. The investigators disclosed additional affiliations with Genentech, Ferring, AstraZeneca, and others. Dr. Axelrad has previously consulted for AbbVie. Dr. Singh has received research funding from AbbVie, Pfizer, and Janssen in the last 24 months, as well as personal fees from Pfizer for an ad hoc grant review.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

The American Gastroenterological Association recently published a Clinical Care Pathway for screening, diagnosis, and treatment of patients with nonalcoholic fatty liver disease (NAFLD).

Recommendations are intended for a spectrum of clinical settings, including primary care, obesity medicine, gastroenterology, hepatology, and endocrinology practices, reported lead author Fasiha Kanwal, MD, of Baylor College of Medicine, Houston, and colleagues.

“Most patients with NAFLD and NASH [nonalcoholic steatohepatitis] are seen in primary care or endocrine clinics,” the authors wrote in Gastroenterology. “Although not all patients with NAFLD/NASH require secondary (i.e., hepatology) care, not knowing which patients might benefit from such care and when to refer them results in inconsistent care processes and possibly poor outcomes. Clinical Care Pathways, with careful explication of each step in screening, diagnosis, and treatment, have been shown to improve the quality of health care delivery in other areas of medicine, [and] are crucial to addressing the often inconsistent care processes characterizing current approaches to NAFLD/NASH.”

The guidance was drafted by a group of 15 multidisciplinary experts from around the world representing the AGA, the American Diabetes Association, the American Osteopathic Association, the Obesity Society, and the Endocrine Society. Recommendations were based on available literature and clinical experience.

The authors recommended a four-step screening process for NAFLD/NASH: Check for risk factors predicting clinically relevant fibrosis (stage F2 or higher), review history and perform relevant laboratory tests, conduct noninvasive liver fibrosis testing, and measure liver stiffness.

Patients at greatest risk for clinically significant fibrosis include those with two or more metabolic risk factors, those with type 2 diabetes, and those with incidentally detected steatosis and/or elevated aminotransferases.

“A recent retrospective cohort study found that patients with hepatic steatosis and elevated alanine aminotransferase had a significantly higher risk of progression to cirrhosis or hepatocellular carcinoma than patients with hepatic steatosis and persistently normal alanine aminotransferase,” the authors noted.

When any of the above risk factors are present, the authors recommended checking the patient’s history for excessive alcohol intake, conducting a complete blood count and liver function tests, and screening for other hepatic and biliary diseases, such as chronic hepatitis C virus infection and liver mass lesions.

If other liver diseases have been ruled out, the first step in liver fibrosis risk stratification involves noninvasive testing, with the authors favoring the Fibrosis-4 (FIB-4) score “because it has been shown to have the best diagnostic accuracy for advanced fibrosis, compared with other noninvasive markers of fibrosis in patients with NAFLD.”

The next step in risk stratification involves liver stiffness measurement (LSM) with FibroScan (vibration controlled transient elastography [VCTE]), or newer modalities, such as bidimensional shear wave elastography or point shear wave elastography, which offer “diagnostic performances at least as good as VCTE.”

According to the publication, patients with NAFLD at low risk of advanced fibrosis (FIB-4 less than 1.3 or LSM less than 8 kPa or liver biopsy F0-F1) can be managed by one provider, such as a primary care provider or endocrinologist, whereas indeterminate-risk patients (FIB-4 of 1.3-2.67 and/or LSM 8-12 kPa and liver biopsy unavailable) and high-risk patients (FIB-4 greater than 2.67 or LSM greater than 12 kPa or liver biopsy F2-F4) should be managed by a multidisciplinary team led by a hepatologist.

Lifestyle intervention, weight loss (if overweight or obese), and cardiovascular disease risk reduction are advised for patients of all risk categories.

“There are no large, long-term behavioral modification or pharmacotherapy studies regarding weight loss in individuals with NAFLD,” the authors wrote. “However, weight loss of any magnitude should be encouraged as beneficial.”

For patients with indeterminate and high risk, NASH pharmacotherapy is recommended, and if needed, diabetes care should involve medications with efficacy in NASH, such as pioglitazone.

“Although we recognize that knowledge is continuing to evolve and that recommendations may change accordingly over time, we believe this Pathway provides accessible, standardized, evidence-based, timely, and testable recommendations that will allow clinicians to care for a rapidly growing population of patients, most of whom are managed in primary care or endocrine clinics,” the authors concluded.

The article was supported by the American Gastroenterological Association, Intercept Pharmaceuticals, Pfizer, and others. The authors disclosed relationships with Novo Nordisk, Eli Lilly, Sanofi, and others.

The number of adenomas per colonoscopy (APC) is inversely correlated with postcolonoscopy colorectal cancer (PCCRC), which supports use of APC as a new quality control measure, according to investigators.

Data from 138 endoscopists showed that patients screened by physicians with higher APCs had significantly lower rates of PCCRC, and an APC of 0.6 offered more protection than either an APC of 0.4 or an adenoma detection rate (ADR) of 25%, reported lead author Joseph C. Anderson, MD, of White River Junction VA Medical Center, Hanover, N.H., and colleagues.

“Unfortunately, APC has never been validated as a quality measure by demonstrating a reduction in PCCRC in exams performed by endoscopists with higher rates,” Dr. Anderson said at the annual meeting of the American College of Gastroenterology.

To this end, Dr. Anderson and colleagues reviewed data from the New Hampshire Colonoscopy Registry (NHCR), including 9,023 screening colonoscopies with a follow-up event 6-60 months after the initial exam. Procedures were conducted by 138 endoscopists in New Hampshire, Vermont, Massachusetts, and Maine.

Three quality measures were analyzed for associations with PCCRC: an APC of 0.4, an APC of 0.6, and an ADR of 25%. Hazard ratios were calculated for all PCCRCs, as well as PCCRCs diagnosed at first follow-up event. Rates were reported for two time periods: 6-36 months and 6-60 months.

From 6 to 60 months, 82 cases of PCCRC were diagnosed, among which 50 were diagnosed between 6 and 36 months.

For both periods, all three quality measures were significantly associated with reductions in PCCRC. The higher APC of 0.6, however, offered greater protection, reducing all PCCRCs by 71% and 61% in the shorter and longer period, respectively. In comparison, the lower APC of 0.4 reduced rates by 63% and 53%, while the ADR benchmark reduced rates by 62% and 42%.

These trends were maintained for PCCRCs diagnosed at first follow-up event. An APC of 0.6 was associated with respective reductions of 79% and 65% for the shorter and longer period, compared with 64% and 57% for the lower APC, and 67% and 49% for ADR.

Additional analysis clarified the relationship between APC level and likelihood of developing PCCRC. In terms of absolute risk, patients screened by an endoscopist with an APC greater than 0.6 had a 0.5% chance of developing PCCRC from 6 to 36 months, compared with 0.7% for an APC of 0.4-0.6, and 2.1% for an APC of less than 0.4 (P = .0001). This pattern held through 60 months, during which time an APC greater than 0.6 was associated with an absolute risk of PCCRC of 0.4%, compared with 0.7% for an APC of 0.4-0.6, and 1.6% for an APC less than 0.4 (P = .0001).

“Our novel data support the use of APC as a quality measure by demonstrating a reduction in PCCRC risk in exams performed by endoscopists with higher APCs,” Dr. Anderson concluded, noting that an APC of 0.6 appeared to offer more protection than an APC of 0.4. “I feel that ... APC as a quality measure, now that we’ve validated it, may be accepted because of its ability to differentiate endoscopists on their adenoma detection skills.”

According to Lawrence Hookey, MD, of Queen’s University, Kingston, Ont., “It’s an important study that will probably contribute to where we’re going forward.”

Dr. Lawrence, chair of the division and medical director of the endoscopy units at Kingston General and Hotel Dieu hospitals, said that APC may overcome the main concern with ADR – that endoscopists who find one adenoma may not be motivated to seek out as many as possible.

“The problem with ADR, in general, is that if you find one polyp, and if ADR is the stat you’re living by, then you don’t need to find any other polyps, and that obviously doesn’t do that patient a favor, necessarily,” Dr. Hookey said in an interview. “It does bring them back sooner for surveillance, but it doesn’t help remove the rest of the polyps that they have. And not that someone is going to find one polyp and turn off the light and pull the scope out, but you may not be looking as hard.”

APC mitigates this issue, he explained, because it determines “whether or not you’re truly clearing things out and getting rid of as many [polyps] as possible.”

Dr. Hookey said that APC is “probably the best” quality control measure on the horizon, and he suggested that more work is needed to determine the optimal benchmark figure, which should ideally be investigated through larger studies.

“I just want to see it in bigger groups,” he said.

The investigators and Dr. Hookey reported no conflicts of interest.

The number of adenomas per colonoscopy (APC) is inversely correlated with postcolonoscopy colorectal cancer (PCCRC), which supports use of APC as a new quality control measure, according to investigators.

Data from 138 endoscopists showed that patients screened by physicians with higher APCs had significantly lower rates of PCCRC, and an APC of 0.6 offered more protection than either an APC of 0.4 or an adenoma detection rate (ADR) of 25%, reported lead author Joseph C. Anderson, MD, of White River Junction VA Medical Center, Hanover, N.H., and colleagues.

“Unfortunately, APC has never been validated as a quality measure by demonstrating a reduction in PCCRC in exams performed by endoscopists with higher rates,” Dr. Anderson said at the annual meeting of the American College of Gastroenterology.

To this end, Dr. Anderson and colleagues reviewed data from the New Hampshire Colonoscopy Registry (NHCR), including 9,023 screening colonoscopies with a follow-up event 6-60 months after the initial exam. Procedures were conducted by 138 endoscopists in New Hampshire, Vermont, Massachusetts, and Maine.

Three quality measures were analyzed for associations with PCCRC: an APC of 0.4, an APC of 0.6, and an ADR of 25%. Hazard ratios were calculated for all PCCRCs, as well as PCCRCs diagnosed at first follow-up event. Rates were reported for two time periods: 6-36 months and 6-60 months.

From 6 to 60 months, 82 cases of PCCRC were diagnosed, among which 50 were diagnosed between 6 and 36 months.

For both periods, all three quality measures were significantly associated with reductions in PCCRC. The higher APC of 0.6, however, offered greater protection, reducing all PCCRCs by 71% and 61% in the shorter and longer period, respectively. In comparison, the lower APC of 0.4 reduced rates by 63% and 53%, while the ADR benchmark reduced rates by 62% and 42%.

These trends were maintained for PCCRCs diagnosed at first follow-up event. An APC of 0.6 was associated with respective reductions of 79% and 65% for the shorter and longer period, compared with 64% and 57% for the lower APC, and 67% and 49% for ADR.

Additional analysis clarified the relationship between APC level and likelihood of developing PCCRC. In terms of absolute risk, patients screened by an endoscopist with an APC greater than 0.6 had a 0.5% chance of developing PCCRC from 6 to 36 months, compared with 0.7% for an APC of 0.4-0.6, and 2.1% for an APC of less than 0.4 (P = .0001). This pattern held through 60 months, during which time an APC greater than 0.6 was associated with an absolute risk of PCCRC of 0.4%, compared with 0.7% for an APC of 0.4-0.6, and 1.6% for an APC less than 0.4 (P = .0001).

“Our novel data support the use of APC as a quality measure by demonstrating a reduction in PCCRC risk in exams performed by endoscopists with higher APCs,” Dr. Anderson concluded, noting that an APC of 0.6 appeared to offer more protection than an APC of 0.4. “I feel that ... APC as a quality measure, now that we’ve validated it, may be accepted because of its ability to differentiate endoscopists on their adenoma detection skills.”

According to Lawrence Hookey, MD, of Queen’s University, Kingston, Ont., “It’s an important study that will probably contribute to where we’re going forward.”

Dr. Lawrence, chair of the division and medical director of the endoscopy units at Kingston General and Hotel Dieu hospitals, said that APC may overcome the main concern with ADR – that endoscopists who find one adenoma may not be motivated to seek out as many as possible.

“The problem with ADR, in general, is that if you find one polyp, and if ADR is the stat you’re living by, then you don’t need to find any other polyps, and that obviously doesn’t do that patient a favor, necessarily,” Dr. Hookey said in an interview. “It does bring them back sooner for surveillance, but it doesn’t help remove the rest of the polyps that they have. And not that someone is going to find one polyp and turn off the light and pull the scope out, but you may not be looking as hard.”

APC mitigates this issue, he explained, because it determines “whether or not you’re truly clearing things out and getting rid of as many [polyps] as possible.”

Dr. Hookey said that APC is “probably the best” quality control measure on the horizon, and he suggested that more work is needed to determine the optimal benchmark figure, which should ideally be investigated through larger studies.

“I just want to see it in bigger groups,” he said.

The investigators and Dr. Hookey reported no conflicts of interest.

The number of adenomas per colonoscopy (APC) is inversely correlated with postcolonoscopy colorectal cancer (PCCRC), which supports use of APC as a new quality control measure, according to investigators.

Data from 138 endoscopists showed that patients screened by physicians with higher APCs had significantly lower rates of PCCRC, and an APC of 0.6 offered more protection than either an APC of 0.4 or an adenoma detection rate (ADR) of 25%, reported lead author Joseph C. Anderson, MD, of White River Junction VA Medical Center, Hanover, N.H., and colleagues.

“Unfortunately, APC has never been validated as a quality measure by demonstrating a reduction in PCCRC in exams performed by endoscopists with higher rates,” Dr. Anderson said at the annual meeting of the American College of Gastroenterology.

To this end, Dr. Anderson and colleagues reviewed data from the New Hampshire Colonoscopy Registry (NHCR), including 9,023 screening colonoscopies with a follow-up event 6-60 months after the initial exam. Procedures were conducted by 138 endoscopists in New Hampshire, Vermont, Massachusetts, and Maine.

Three quality measures were analyzed for associations with PCCRC: an APC of 0.4, an APC of 0.6, and an ADR of 25%. Hazard ratios were calculated for all PCCRCs, as well as PCCRCs diagnosed at first follow-up event. Rates were reported for two time periods: 6-36 months and 6-60 months.

From 6 to 60 months, 82 cases of PCCRC were diagnosed, among which 50 were diagnosed between 6 and 36 months.

For both periods, all three quality measures were significantly associated with reductions in PCCRC. The higher APC of 0.6, however, offered greater protection, reducing all PCCRCs by 71% and 61% in the shorter and longer period, respectively. In comparison, the lower APC of 0.4 reduced rates by 63% and 53%, while the ADR benchmark reduced rates by 62% and 42%.

These trends were maintained for PCCRCs diagnosed at first follow-up event. An APC of 0.6 was associated with respective reductions of 79% and 65% for the shorter and longer period, compared with 64% and 57% for the lower APC, and 67% and 49% for ADR.

Additional analysis clarified the relationship between APC level and likelihood of developing PCCRC. In terms of absolute risk, patients screened by an endoscopist with an APC greater than 0.6 had a 0.5% chance of developing PCCRC from 6 to 36 months, compared with 0.7% for an APC of 0.4-0.6, and 2.1% for an APC of less than 0.4 (P = .0001). This pattern held through 60 months, during which time an APC greater than 0.6 was associated with an absolute risk of PCCRC of 0.4%, compared with 0.7% for an APC of 0.4-0.6, and 1.6% for an APC less than 0.4 (P = .0001).

“Our novel data support the use of APC as a quality measure by demonstrating a reduction in PCCRC risk in exams performed by endoscopists with higher APCs,” Dr. Anderson concluded, noting that an APC of 0.6 appeared to offer more protection than an APC of 0.4. “I feel that ... APC as a quality measure, now that we’ve validated it, may be accepted because of its ability to differentiate endoscopists on their adenoma detection skills.”

According to Lawrence Hookey, MD, of Queen’s University, Kingston, Ont., “It’s an important study that will probably contribute to where we’re going forward.”

Dr. Lawrence, chair of the division and medical director of the endoscopy units at Kingston General and Hotel Dieu hospitals, said that APC may overcome the main concern with ADR – that endoscopists who find one adenoma may not be motivated to seek out as many as possible.

“The problem with ADR, in general, is that if you find one polyp, and if ADR is the stat you’re living by, then you don’t need to find any other polyps, and that obviously doesn’t do that patient a favor, necessarily,” Dr. Hookey said in an interview. “It does bring them back sooner for surveillance, but it doesn’t help remove the rest of the polyps that they have. And not that someone is going to find one polyp and turn off the light and pull the scope out, but you may not be looking as hard.”

APC mitigates this issue, he explained, because it determines “whether or not you’re truly clearing things out and getting rid of as many [polyps] as possible.”

Dr. Hookey said that APC is “probably the best” quality control measure on the horizon, and he suggested that more work is needed to determine the optimal benchmark figure, which should ideally be investigated through larger studies.

“I just want to see it in bigger groups,” he said.

The investigators and Dr. Hookey reported no conflicts of interest.

Most patients with inflammatory bowel disease (IBD) develop a humoral immune response after completing an mRNA SARS-CoV-2 vaccine series, according to data from almost 800 patients.

Choreograph/iStock/Getty Images

Anti–receptor binding domain IgG antibodies specific to SARS-CoV-2 were detectable in 95% of patients, with “generally similar” results across vaccine type, age group, and medication class, apart from corticosteroid users, who had an 86% antibody detection rate, reported lead author Kimberly N. Weaver, MD, of the University of North Carolina at Chapel Hill, and colleagues.

“Patients with IBD on immunosuppressive medications have the potential for attenuated response to the SARS-CoV-2 vaccination,” Dr. Weaver said at the annual meeting of the American College of Gastroenterology.

In support of this possibility, Dr. Weaver cited two recent trials from earlier in 2021: one demonstrated blunted antibody responses in IBD patients taking infliximab, while the other showed that full vaccination was less effective at preventing SARS-CoV-2 infection among patients with IBD than nonimmunosuppressed individuals.

To better characterize antibody responses after receiving an mRNA vaccination series, Dr. Weaver and colleagues launched the PREVENT-COVID trial, including the present dataset of 787 patients with IBD older than 12 years, all of whom provided serum samples 8 weeks after completing an mRNA vaccine series. Patients with positive nucleocapsid antibody (indicating prior infection), and/or those who reported prior COVID-19 infection, were excluded. Most patients were White (95%) and female (73%), with an average age of 48 years. Slightly more patients received the BNT162b2 vaccine than the mRNA-1273 vaccine (58% vs. 42%).

At 8 weeks, 752 out of 787 patients had detectable antibodies (95%). Antibody rates were highest among patients receiving vedolizumab monotherapy (n = 83; 99%) or ustekinumab monotherapy (n = 102; 99%), followed by mercaptopurine, azathioprine, or methotrexate monotherapy (n = 67; 97%); anti–tumor necrosis factor monotherapy (n = 270; 96%); mesalamine, sulfasalazine, or budesonide monotherapy or no medication (n = 143; 95%); and finally anti-TNF/immunosuppressive combination therapy (n = 75; 86%). Median and mean antibody titers were lowest for anti-TNF combination therapy and highest for vedolizumab.

Thirty-five patients taking corticosteroids had an antibody detection rate of 85.7% (95% CI, 70.6-93.7), compared with 95.9% (95% CI, 94.2-97.1) among nonsteroid users. In contrast, antibody detection rates were not significantly affected by age or vaccine type.

“Reassuringly, most IBD medications do not prevent an initial antibody response after SARS-CoV-2 vaccination, and this is unlike other classes of immune suppression such as B-cell depletion therapy,” Dr. Weaver concluded. “Additional data are forthcoming on a larger subset of participants in the PREVENT-COVID study which will allow for analysis of factors associated with humoral immune response and potential optimization of immunization strategies.” She described a dataset of about 500 IBD patients in which booster vaccines overcame poor antibody responses to the initial vaccine series.
 

‘The data we need’

Serre-yu Wong, MD, PhD, of Icahn School of Medicine at Mount Sinai, New York, agreed that the findings should offer some reassurance to patients with IBD and their care providers.

“At the end of the day we have really nice seroconversion rates for the IBD population,” Dr. Wong said.

In April 2021, Dr. Wong and the ICARUS-IBD Working Group published a similar report of 48 patients with IBD receiving biologic therapies, among whom the seroconversion rate was 100%.

“A lot of the early data, including ours, are on infusion medications, and that’s sort of a practical thing because those were the only patients we could get samples from, but [Dr. Weaver and colleagues] were able to get samples from patients not on medications, on oral medications, and on other injection medications that people can take at home, and these are really the data we need for all of our other IBD patients,” Dr. Wong said.

Dr. Wong highlighted that both trials showed some IBD patients generating “very, very high” titers, many of them above the threshold needed for donating convalescent plasma for COVID-19 treatment; still, exact titer levels needed to protect against SARS-CoV-2 infection remain unclear.

“This is going to require longitudinal studies,” Dr. Wong said. “We can’t answer that perfectly right now. We don’t know the magic level of antibodies. I don’t know if you need a titer of 1:100 or 1:1,000.”

Although postvaccination antibody testing is not recommended by the Centers for Disease Control and Prevention, Dr. Wong said that “many patients” check their titers anyway, leading to anxiety if antibodies are low or undetectable.

“I know that it’s very disconcerting sometimes when you don’t see an antibody response, and this is one of the hardest things to try to explain to patients,” Dr. Wong said. “[It’s necessary] to have a frank discussion about the fact that we don’t know the magic level of antibodies, and that there are also other parts of the immune system that we haven’t tested with antibodies. We haven’t tested the T-cell response, and we do know you can have a T-cell response even if you don’t have a B-cell response.”

Dr. Wong suggested that more work is needed to determine the impact of the IBD disease process on susceptibility to SARS-CoV-2 infection, and the rates of antibody responses for the various other vaccines being used around the world.

The PREVENT-COVID study was supported by the Leona M. and Harry B. Helmsley Charitable Trust. The investigators disclosed additional relationships with AbbVie, Johnson & Johnson, Genentech, and others. Dr. Wong reported no relevant conflicts of interest.

This article was updated Oct. 28, 2021.

Most patients with inflammatory bowel disease (IBD) develop a humoral immune response after completing an mRNA SARS-CoV-2 vaccine series, according to data from almost 800 patients.

Choreograph/iStock/Getty Images

Anti–receptor binding domain IgG antibodies specific to SARS-CoV-2 were detectable in 95% of patients, with “generally similar” results across vaccine type, age group, and medication class, apart from corticosteroid users, who had an 86% antibody detection rate, reported lead author Kimberly N. Weaver, MD, of the University of North Carolina at Chapel Hill, and colleagues.

“Patients with IBD on immunosuppressive medications have the potential for attenuated response to the SARS-CoV-2 vaccination,” Dr. Weaver said at the annual meeting of the American College of Gastroenterology.

In support of this possibility, Dr. Weaver cited two recent trials from earlier in 2021: one demonstrated blunted antibody responses in IBD patients taking infliximab, while the other showed that full vaccination was less effective at preventing SARS-CoV-2 infection among patients with IBD than nonimmunosuppressed individuals.

To better characterize antibody responses after receiving an mRNA vaccination series, Dr. Weaver and colleagues launched the PREVENT-COVID trial, including the present dataset of 787 patients with IBD older than 12 years, all of whom provided serum samples 8 weeks after completing an mRNA vaccine series. Patients with positive nucleocapsid antibody (indicating prior infection), and/or those who reported prior COVID-19 infection, were excluded. Most patients were White (95%) and female (73%), with an average age of 48 years. Slightly more patients received the BNT162b2 vaccine than the mRNA-1273 vaccine (58% vs. 42%).

At 8 weeks, 752 out of 787 patients had detectable antibodies (95%). Antibody rates were highest among patients receiving vedolizumab monotherapy (n = 83; 99%) or ustekinumab monotherapy (n = 102; 99%), followed by mercaptopurine, azathioprine, or methotrexate monotherapy (n = 67; 97%); anti–tumor necrosis factor monotherapy (n = 270; 96%); mesalamine, sulfasalazine, or budesonide monotherapy or no medication (n = 143; 95%); and finally anti-TNF/immunosuppressive combination therapy (n = 75; 86%). Median and mean antibody titers were lowest for anti-TNF combination therapy and highest for vedolizumab.

Thirty-five patients taking corticosteroids had an antibody detection rate of 85.7% (95% CI, 70.6-93.7), compared with 95.9% (95% CI, 94.2-97.1) among nonsteroid users. In contrast, antibody detection rates were not significantly affected by age or vaccine type.

“Reassuringly, most IBD medications do not prevent an initial antibody response after SARS-CoV-2 vaccination, and this is unlike other classes of immune suppression such as B-cell depletion therapy,” Dr. Weaver concluded. “Additional data are forthcoming on a larger subset of participants in the PREVENT-COVID study which will allow for analysis of factors associated with humoral immune response and potential optimization of immunization strategies.” She described a dataset of about 500 IBD patients in which booster vaccines overcame poor antibody responses to the initial vaccine series.
 

‘The data we need’

Serre-yu Wong, MD, PhD, of Icahn School of Medicine at Mount Sinai, New York, agreed that the findings should offer some reassurance to patients with IBD and their care providers.

“At the end of the day we have really nice seroconversion rates for the IBD population,” Dr. Wong said.

In April 2021, Dr. Wong and the ICARUS-IBD Working Group published a similar report of 48 patients with IBD receiving biologic therapies, among whom the seroconversion rate was 100%.

“A lot of the early data, including ours, are on infusion medications, and that’s sort of a practical thing because those were the only patients we could get samples from, but [Dr. Weaver and colleagues] were able to get samples from patients not on medications, on oral medications, and on other injection medications that people can take at home, and these are really the data we need for all of our other IBD patients,” Dr. Wong said.

Dr. Wong highlighted that both trials showed some IBD patients generating “very, very high” titers, many of them above the threshold needed for donating convalescent plasma for COVID-19 treatment; still, exact titer levels needed to protect against SARS-CoV-2 infection remain unclear.

“This is going to require longitudinal studies,” Dr. Wong said. “We can’t answer that perfectly right now. We don’t know the magic level of antibodies. I don’t know if you need a titer of 1:100 or 1:1,000.”

Although postvaccination antibody testing is not recommended by the Centers for Disease Control and Prevention, Dr. Wong said that “many patients” check their titers anyway, leading to anxiety if antibodies are low or undetectable.

“I know that it’s very disconcerting sometimes when you don’t see an antibody response, and this is one of the hardest things to try to explain to patients,” Dr. Wong said. “[It’s necessary] to have a frank discussion about the fact that we don’t know the magic level of antibodies, and that there are also other parts of the immune system that we haven’t tested with antibodies. We haven’t tested the T-cell response, and we do know you can have a T-cell response even if you don’t have a B-cell response.”

Dr. Wong suggested that more work is needed to determine the impact of the IBD disease process on susceptibility to SARS-CoV-2 infection, and the rates of antibody responses for the various other vaccines being used around the world.

The PREVENT-COVID study was supported by the Leona M. and Harry B. Helmsley Charitable Trust. The investigators disclosed additional relationships with AbbVie, Johnson & Johnson, Genentech, and others. Dr. Wong reported no relevant conflicts of interest.

This article was updated Oct. 28, 2021.

Most patients with inflammatory bowel disease (IBD) develop a humoral immune response after completing an mRNA SARS-CoV-2 vaccine series, according to data from almost 800 patients.

Choreograph/iStock/Getty Images

Anti–receptor binding domain IgG antibodies specific to SARS-CoV-2 were detectable in 95% of patients, with “generally similar” results across vaccine type, age group, and medication class, apart from corticosteroid users, who had an 86% antibody detection rate, reported lead author Kimberly N. Weaver, MD, of the University of North Carolina at Chapel Hill, and colleagues.

“Patients with IBD on immunosuppressive medications have the potential for attenuated response to the SARS-CoV-2 vaccination,” Dr. Weaver said at the annual meeting of the American College of Gastroenterology.

In support of this possibility, Dr. Weaver cited two recent trials from earlier in 2021: one demonstrated blunted antibody responses in IBD patients taking infliximab, while the other showed that full vaccination was less effective at preventing SARS-CoV-2 infection among patients with IBD than nonimmunosuppressed individuals.

To better characterize antibody responses after receiving an mRNA vaccination series, Dr. Weaver and colleagues launched the PREVENT-COVID trial, including the present dataset of 787 patients with IBD older than 12 years, all of whom provided serum samples 8 weeks after completing an mRNA vaccine series. Patients with positive nucleocapsid antibody (indicating prior infection), and/or those who reported prior COVID-19 infection, were excluded. Most patients were White (95%) and female (73%), with an average age of 48 years. Slightly more patients received the BNT162b2 vaccine than the mRNA-1273 vaccine (58% vs. 42%).

At 8 weeks, 752 out of 787 patients had detectable antibodies (95%). Antibody rates were highest among patients receiving vedolizumab monotherapy (n = 83; 99%) or ustekinumab monotherapy (n = 102; 99%), followed by mercaptopurine, azathioprine, or methotrexate monotherapy (n = 67; 97%); anti–tumor necrosis factor monotherapy (n = 270; 96%); mesalamine, sulfasalazine, or budesonide monotherapy or no medication (n = 143; 95%); and finally anti-TNF/immunosuppressive combination therapy (n = 75; 86%). Median and mean antibody titers were lowest for anti-TNF combination therapy and highest for vedolizumab.

Thirty-five patients taking corticosteroids had an antibody detection rate of 85.7% (95% CI, 70.6-93.7), compared with 95.9% (95% CI, 94.2-97.1) among nonsteroid users. In contrast, antibody detection rates were not significantly affected by age or vaccine type.

“Reassuringly, most IBD medications do not prevent an initial antibody response after SARS-CoV-2 vaccination, and this is unlike other classes of immune suppression such as B-cell depletion therapy,” Dr. Weaver concluded. “Additional data are forthcoming on a larger subset of participants in the PREVENT-COVID study which will allow for analysis of factors associated with humoral immune response and potential optimization of immunization strategies.” She described a dataset of about 500 IBD patients in which booster vaccines overcame poor antibody responses to the initial vaccine series.
 

‘The data we need’

Serre-yu Wong, MD, PhD, of Icahn School of Medicine at Mount Sinai, New York, agreed that the findings should offer some reassurance to patients with IBD and their care providers.

“At the end of the day we have really nice seroconversion rates for the IBD population,” Dr. Wong said.

In April 2021, Dr. Wong and the ICARUS-IBD Working Group published a similar report of 48 patients with IBD receiving biologic therapies, among whom the seroconversion rate was 100%.

“A lot of the early data, including ours, are on infusion medications, and that’s sort of a practical thing because those were the only patients we could get samples from, but [Dr. Weaver and colleagues] were able to get samples from patients not on medications, on oral medications, and on other injection medications that people can take at home, and these are really the data we need for all of our other IBD patients,” Dr. Wong said.

Dr. Wong highlighted that both trials showed some IBD patients generating “very, very high” titers, many of them above the threshold needed for donating convalescent plasma for COVID-19 treatment; still, exact titer levels needed to protect against SARS-CoV-2 infection remain unclear.

“This is going to require longitudinal studies,” Dr. Wong said. “We can’t answer that perfectly right now. We don’t know the magic level of antibodies. I don’t know if you need a titer of 1:100 or 1:1,000.”

Although postvaccination antibody testing is not recommended by the Centers for Disease Control and Prevention, Dr. Wong said that “many patients” check their titers anyway, leading to anxiety if antibodies are low or undetectable.

“I know that it’s very disconcerting sometimes when you don’t see an antibody response, and this is one of the hardest things to try to explain to patients,” Dr. Wong said. “[It’s necessary] to have a frank discussion about the fact that we don’t know the magic level of antibodies, and that there are also other parts of the immune system that we haven’t tested with antibodies. We haven’t tested the T-cell response, and we do know you can have a T-cell response even if you don’t have a B-cell response.”

Dr. Wong suggested that more work is needed to determine the impact of the IBD disease process on susceptibility to SARS-CoV-2 infection, and the rates of antibody responses for the various other vaccines being used around the world.

The PREVENT-COVID study was supported by the Leona M. and Harry B. Helmsley Charitable Trust. The investigators disclosed additional relationships with AbbVie, Johnson & Johnson, Genentech, and others. Dr. Wong reported no relevant conflicts of interest.

This article was updated Oct. 28, 2021.

Using stool samples to test for Helicobacter pylori antibiotic resistance provides highly similar results to those of gastric biopsy samples, which suggests that stool testing may be a safer, more convenient, and more cost-effective option, according to investigators.

sgame/thinkstockphotos.com

Head-to-head testing for resistance-associated mutations using next-generation sequencing (NGS) showed 92% concordance between the two sample types, with 100% technical success among polymerase chain reaction (PCR)–positive stool samples, lead author Steven Moss, MD, of Brown University, Providence, R.I., and colleagues reported.

“H. pylori eradication rates have declined largely due to rising antimicrobial resistance worldwide,” Dr. Moss said at the annual meeting of the American College of Gastroenterology. “There is therefore a need for rapid, accurate, reliable antibiotic resistance testing.”

According to Dr. Moss, molecular resistance testing of gastric biopsies yields similar results to culture-based testing of gastric biopsies, but endoscopic sample collection remains inconvenient and relatively costly, so “it is not commonly performed in many GI practices.

“Whether reliable resistance testing by NGS is possible from stool samples remains unclear,” Dr. Moss said.

To explore this possibility, Dr. Moss and colleagues recruited 262 patients scheduled for upper endoscopy at four sites in the United States. From each patient, two gastric biopsies were taken, and within 2 weeks of the procedure, prior to starting anti–H. pylori therapy, one stool sample was collected.

For gastric biopsy samples, H. pylori positivity was confirmed by PCR, whereas positivity in stool samples was confirmed by both fecal antigen testing and PCR. After confirmation, NGS was conducted, with screening for resistance-associated mutations to six commonly used antibiotics: clarithromycin, levofloxacin, metronidazole, tetracycline, amoxicillin, and rifabutin.

Out of 262 patients, 73 tested positive for H. pylori via stool testing; however, 2 of these patients had inadequate gastric DNA for analysis, leaving 71 patients in the evaluable dataset. Within this group, samples from 50 patients (70.4%) had at least one resistance-association mutation.

Among all 71 individuals, 65 patients (91.5%) had fully concordant results between the two sample types. In four out of the six discordant cases, there was only one difference in antibiotic-associated mutations. Concordance ranged from 89% for metronidazole mutations to 100% for tetracycline, amoxicillin, and rifabutin mutations.

“It is now possible to rapidly obtain susceptibility data without endoscopy,” Dr. Moss concluded. “Using NGS to determine H. pylori antibiotic resistance using stool obviates the cost, inconvenience, and risks of endoscopy resistance profiling.”

Dr. Moss noted that the cost of the stool-based test, through study sponsor American Molecular Laboratories, is about $450, and that the company is “working with various insurance companies to try to get [the test] reimbursed.”

For cases of H. pylori infection without resistance testing results, Dr. Moss recommended first-line treatment with quadruple bismuth–based therapy; however, he noted that “most gastroenterologists, in all kinds of practice, are not measuring their eradication success rate ... so it’s really difficult to know if your best guess is really the appropriate treatment.”

According to Lukasz Kwapisz, MD, of Baylor College of Medicine, Houston, the concordance results are “encouraging,” and suggest that stool-based testing “could be much easier for the patient and the clinician” to find ways to eradicate H. pylori infection.

Dr. Kwapisz predicted that it will take additional successful studies, as well as real-world data, to convert clinicians to the new approach. He suggested that the transition may be gradual, like the adoption of fecal calprotectin testing.

“I don’t know if it’s one singular defining study that will tell you: ‘Okay, we all have to use this [stool-based resistance testing],’ ” he said. “It kind of happens over time – over a 2- or 3-year stretch, I would think, with positive results.”

The study was supported by American Molecular Labs. The investigators disclosed additional relationships with Takeda, Phathom, and Redhill. Dr. Kwapisz reported no conflicts of interest.

Using stool samples to test for Helicobacter pylori antibiotic resistance provides highly similar results to those of gastric biopsy samples, which suggests that stool testing may be a safer, more convenient, and more cost-effective option, according to investigators.

sgame/thinkstockphotos.com

Head-to-head testing for resistance-associated mutations using next-generation sequencing (NGS) showed 92% concordance between the two sample types, with 100% technical success among polymerase chain reaction (PCR)–positive stool samples, lead author Steven Moss, MD, of Brown University, Providence, R.I., and colleagues reported.

“H. pylori eradication rates have declined largely due to rising antimicrobial resistance worldwide,” Dr. Moss said at the annual meeting of the American College of Gastroenterology. “There is therefore a need for rapid, accurate, reliable antibiotic resistance testing.”

According to Dr. Moss, molecular resistance testing of gastric biopsies yields similar results to culture-based testing of gastric biopsies, but endoscopic sample collection remains inconvenient and relatively costly, so “it is not commonly performed in many GI practices.

“Whether reliable resistance testing by NGS is possible from stool samples remains unclear,” Dr. Moss said.

To explore this possibility, Dr. Moss and colleagues recruited 262 patients scheduled for upper endoscopy at four sites in the United States. From each patient, two gastric biopsies were taken, and within 2 weeks of the procedure, prior to starting anti–H. pylori therapy, one stool sample was collected.

For gastric biopsy samples, H. pylori positivity was confirmed by PCR, whereas positivity in stool samples was confirmed by both fecal antigen testing and PCR. After confirmation, NGS was conducted, with screening for resistance-associated mutations to six commonly used antibiotics: clarithromycin, levofloxacin, metronidazole, tetracycline, amoxicillin, and rifabutin.

Out of 262 patients, 73 tested positive for H. pylori via stool testing; however, 2 of these patients had inadequate gastric DNA for analysis, leaving 71 patients in the evaluable dataset. Within this group, samples from 50 patients (70.4%) had at least one resistance-association mutation.

Among all 71 individuals, 65 patients (91.5%) had fully concordant results between the two sample types. In four out of the six discordant cases, there was only one difference in antibiotic-associated mutations. Concordance ranged from 89% for metronidazole mutations to 100% for tetracycline, amoxicillin, and rifabutin mutations.

“It is now possible to rapidly obtain susceptibility data without endoscopy,” Dr. Moss concluded. “Using NGS to determine H. pylori antibiotic resistance using stool obviates the cost, inconvenience, and risks of endoscopy resistance profiling.”

Dr. Moss noted that the cost of the stool-based test, through study sponsor American Molecular Laboratories, is about $450, and that the company is “working with various insurance companies to try to get [the test] reimbursed.”

For cases of H. pylori infection without resistance testing results, Dr. Moss recommended first-line treatment with quadruple bismuth–based therapy; however, he noted that “most gastroenterologists, in all kinds of practice, are not measuring their eradication success rate ... so it’s really difficult to know if your best guess is really the appropriate treatment.”

According to Lukasz Kwapisz, MD, of Baylor College of Medicine, Houston, the concordance results are “encouraging,” and suggest that stool-based testing “could be much easier for the patient and the clinician” to find ways to eradicate H. pylori infection.

Dr. Kwapisz predicted that it will take additional successful studies, as well as real-world data, to convert clinicians to the new approach. He suggested that the transition may be gradual, like the adoption of fecal calprotectin testing.

“I don’t know if it’s one singular defining study that will tell you: ‘Okay, we all have to use this [stool-based resistance testing],’ ” he said. “It kind of happens over time – over a 2- or 3-year stretch, I would think, with positive results.”

The study was supported by American Molecular Labs. The investigators disclosed additional relationships with Takeda, Phathom, and Redhill. Dr. Kwapisz reported no conflicts of interest.

Using stool samples to test for Helicobacter pylori antibiotic resistance provides highly similar results to those of gastric biopsy samples, which suggests that stool testing may be a safer, more convenient, and more cost-effective option, according to investigators.

sgame/thinkstockphotos.com

Head-to-head testing for resistance-associated mutations using next-generation sequencing (NGS) showed 92% concordance between the two sample types, with 100% technical success among polymerase chain reaction (PCR)–positive stool samples, lead author Steven Moss, MD, of Brown University, Providence, R.I., and colleagues reported.

“H. pylori eradication rates have declined largely due to rising antimicrobial resistance worldwide,” Dr. Moss said at the annual meeting of the American College of Gastroenterology. “There is therefore a need for rapid, accurate, reliable antibiotic resistance testing.”

According to Dr. Moss, molecular resistance testing of gastric biopsies yields similar results to culture-based testing of gastric biopsies, but endoscopic sample collection remains inconvenient and relatively costly, so “it is not commonly performed in many GI practices.

“Whether reliable resistance testing by NGS is possible from stool samples remains unclear,” Dr. Moss said.

To explore this possibility, Dr. Moss and colleagues recruited 262 patients scheduled for upper endoscopy at four sites in the United States. From each patient, two gastric biopsies were taken, and within 2 weeks of the procedure, prior to starting anti–H. pylori therapy, one stool sample was collected.

For gastric biopsy samples, H. pylori positivity was confirmed by PCR, whereas positivity in stool samples was confirmed by both fecal antigen testing and PCR. After confirmation, NGS was conducted, with screening for resistance-associated mutations to six commonly used antibiotics: clarithromycin, levofloxacin, metronidazole, tetracycline, amoxicillin, and rifabutin.

Out of 262 patients, 73 tested positive for H. pylori via stool testing; however, 2 of these patients had inadequate gastric DNA for analysis, leaving 71 patients in the evaluable dataset. Within this group, samples from 50 patients (70.4%) had at least one resistance-association mutation.

Among all 71 individuals, 65 patients (91.5%) had fully concordant results between the two sample types. In four out of the six discordant cases, there was only one difference in antibiotic-associated mutations. Concordance ranged from 89% for metronidazole mutations to 100% for tetracycline, amoxicillin, and rifabutin mutations.

“It is now possible to rapidly obtain susceptibility data without endoscopy,” Dr. Moss concluded. “Using NGS to determine H. pylori antibiotic resistance using stool obviates the cost, inconvenience, and risks of endoscopy resistance profiling.”

Dr. Moss noted that the cost of the stool-based test, through study sponsor American Molecular Laboratories, is about $450, and that the company is “working with various insurance companies to try to get [the test] reimbursed.”

For cases of H. pylori infection without resistance testing results, Dr. Moss recommended first-line treatment with quadruple bismuth–based therapy; however, he noted that “most gastroenterologists, in all kinds of practice, are not measuring their eradication success rate ... so it’s really difficult to know if your best guess is really the appropriate treatment.”

According to Lukasz Kwapisz, MD, of Baylor College of Medicine, Houston, the concordance results are “encouraging,” and suggest that stool-based testing “could be much easier for the patient and the clinician” to find ways to eradicate H. pylori infection.

Dr. Kwapisz predicted that it will take additional successful studies, as well as real-world data, to convert clinicians to the new approach. He suggested that the transition may be gradual, like the adoption of fecal calprotectin testing.

“I don’t know if it’s one singular defining study that will tell you: ‘Okay, we all have to use this [stool-based resistance testing],’ ” he said. “It kind of happens over time – over a 2- or 3-year stretch, I would think, with positive results.”

The study was supported by American Molecular Labs. The investigators disclosed additional relationships with Takeda, Phathom, and Redhill. Dr. Kwapisz reported no conflicts of interest.

A statewide educational initiative in Maryland was associated with a significant reduction in cesarean delivery rates over 30 months, although program implementation was widely variable across participating hospitals, according to investigators.

Cesarean deliveries dropped 1.6% among nulliparous, term, singleton, vertex births, falling short of the 3.2% reduction recently achieved by a similar program in California, reported lead author Jennifer A. Callaghan-Koru, PhD, of the University of Maryland, Baltimore County, and colleagues.

“Although cesarean delivery can be lifesaving, evidence suggests that there is no benefit to maternal health when national cesarean delivery rates are higher than 20 per 100 live births,” the investigators wrote in Obstetrics & Gynecology.

They noted that cesarean delivery rates in the United States rose dramatically between 1996 and 2006, from 20.7% to 32.9%, before falling back to 31.7% in 2019.

According to the investigators, high cesarean delivery rates have drawn action from a roster of stakeholders, including the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), the Department of Health and Human Services, the Joint Commission, and the Council on Patient Safety in Women’s Health Care.

The latter group created an evidence-based obstetric patient safety bundle that was used in the present study. The investigators recruited 31 out of 32 birthing hospitals in Maryland, and over the course of 30 months, educated the participating hospitals on the practices recommended by the bundle, via in-person and remote training.

To measure implementation and associated outcomes, the investigators used a data portal provided by the ACOG Alliance for Innovation in Maternal Health (AIM) program, which supports adoption of the council’s safety bundle nationwide. Data included number of births; number of cesarean births; overall cesarean delivery rates; cesarean rates among nulliparous, term, singleton, vertex births; cesarean rates among nulliparous, term, singleton, vertex inductions; as well as severe maternal morbidity rates.

Among the 26 safety practices in the bundle, hospitals reported current use of 7 (median) before the program began, with a range from 0 to 23. During the 30-month collaboration, hospitals added a median of 4 practices, ranging from 0 to 17.

Concurrently, cesarean delivery rates for nulliparous, term, singleton, vertex births dropped from 26.9% to 28.5% (P = .011), while rates for inductions dropped to a greater degree, from 36.1% to 31.3% (P less than .001). Further analysis showed that greater reductions in rates of cesarean delivery were associated with adoption of practices in the “Response” domain.

“The Response domain has the largest number of practices that standardize clinical care, including induction scheduling, diagnosis and treatment of labor dystocia and failed induction, and interpretation of fetal heart rate patterns,” the investigators wrote. “The important role of standardizing care is consistent with a Cochrane review that found moderately strong evidence that the implementation of clinical practice guidelines, alongside feedback to clinicians (e.g., second opinions, audit and feedback of rates), can reduce cesarean delivery.”

Dr. Callaghan-Koru and colleagues noted the high variability of implementation among hospitals, which could explain why statewide reductions weren’t more dramatic.

“Other evaluations of perinatal quality improvement collaboratives have also found that some hospitals get left behind in these efforts, without making considerable progress and improving outcomes,” they wrote. “Given that work by state perinatal quality improvement collaboratives represents a primary national strategy for reducing maternal morbidity and mortality, it is critically important to conduct further implementation research to identify determinants of success and strategies to support all participating hospitals to make improvements.”

According to Iris Krishna, MD, of Emory University, Atlanta, each state’s starting point may predict how successful similar programs will be.

“The safe reduction in the cesarean delivery rate will vary by state,” Dr. Krishna said in a written comment. “States that have a well-established perinatal quality collaborative that have the support on the provider, hospital, and statewide level are more likely to successfully implement strategies and see a statistically significant decrease.”

She went on to emphasize the importance of collaboration across multiple levels of organization, and across a variety of health care providers and administrators.

“Successful implementation requires a multidisciplinary team (physicians, nurses, quality improvement officers) and a multifaceted approach (statewide policies),” Dr. Krishna said. “Key stakeholders will need to ‘buy in’ or be willing to support the policy and practice change to ensure its success. To address obstacles, initiatives to support vaginal birth are important, such as provider training on labor and support techniques, criteria for diagnosis of and management of labor dystocia and arrest disorders, standard responses to abnormal fetal heart rate patterns, and availability of expertise to lessen the need for cesarean delivery, such as breech version, instrumented delivery, and twin delivery protocols. It is also important for hospitals to a have a mentor model of quality improvement and shared learning strategies that work.”

Dr. Krishna agreed with the investigators that more work is necessary to determine best strategies for future intervention.

“Research is needed in identifying determinants of success and sustainment,” she said.

Dr. Burke received funding from her employer, Trinity Health, to conduct a pilot study concerning blood loss.

A statewide educational initiative in Maryland was associated with a significant reduction in cesarean delivery rates over 30 months, although program implementation was widely variable across participating hospitals, according to investigators.

Cesarean deliveries dropped 1.6% among nulliparous, term, singleton, vertex births, falling short of the 3.2% reduction recently achieved by a similar program in California, reported lead author Jennifer A. Callaghan-Koru, PhD, of the University of Maryland, Baltimore County, and colleagues.

“Although cesarean delivery can be lifesaving, evidence suggests that there is no benefit to maternal health when national cesarean delivery rates are higher than 20 per 100 live births,” the investigators wrote in Obstetrics & Gynecology.

They noted that cesarean delivery rates in the United States rose dramatically between 1996 and 2006, from 20.7% to 32.9%, before falling back to 31.7% in 2019.

According to the investigators, high cesarean delivery rates have drawn action from a roster of stakeholders, including the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), the Department of Health and Human Services, the Joint Commission, and the Council on Patient Safety in Women’s Health Care.

The latter group created an evidence-based obstetric patient safety bundle that was used in the present study. The investigators recruited 31 out of 32 birthing hospitals in Maryland, and over the course of 30 months, educated the participating hospitals on the practices recommended by the bundle, via in-person and remote training.

To measure implementation and associated outcomes, the investigators used a data portal provided by the ACOG Alliance for Innovation in Maternal Health (AIM) program, which supports adoption of the council’s safety bundle nationwide. Data included number of births; number of cesarean births; overall cesarean delivery rates; cesarean rates among nulliparous, term, singleton, vertex births; cesarean rates among nulliparous, term, singleton, vertex inductions; as well as severe maternal morbidity rates.

Among the 26 safety practices in the bundle, hospitals reported current use of 7 (median) before the program began, with a range from 0 to 23. During the 30-month collaboration, hospitals added a median of 4 practices, ranging from 0 to 17.

Concurrently, cesarean delivery rates for nulliparous, term, singleton, vertex births dropped from 26.9% to 28.5% (P = .011), while rates for inductions dropped to a greater degree, from 36.1% to 31.3% (P less than .001). Further analysis showed that greater reductions in rates of cesarean delivery were associated with adoption of practices in the “Response” domain.

“The Response domain has the largest number of practices that standardize clinical care, including induction scheduling, diagnosis and treatment of labor dystocia and failed induction, and interpretation of fetal heart rate patterns,” the investigators wrote. “The important role of standardizing care is consistent with a Cochrane review that found moderately strong evidence that the implementation of clinical practice guidelines, alongside feedback to clinicians (e.g., second opinions, audit and feedback of rates), can reduce cesarean delivery.”

Dr. Callaghan-Koru and colleagues noted the high variability of implementation among hospitals, which could explain why statewide reductions weren’t more dramatic.

“Other evaluations of perinatal quality improvement collaboratives have also found that some hospitals get left behind in these efforts, without making considerable progress and improving outcomes,” they wrote. “Given that work by state perinatal quality improvement collaboratives represents a primary national strategy for reducing maternal morbidity and mortality, it is critically important to conduct further implementation research to identify determinants of success and strategies to support all participating hospitals to make improvements.”

According to Iris Krishna, MD, of Emory University, Atlanta, each state’s starting point may predict how successful similar programs will be.

“The safe reduction in the cesarean delivery rate will vary by state,” Dr. Krishna said in a written comment. “States that have a well-established perinatal quality collaborative that have the support on the provider, hospital, and statewide level are more likely to successfully implement strategies and see a statistically significant decrease.”

She went on to emphasize the importance of collaboration across multiple levels of organization, and across a variety of health care providers and administrators.

“Successful implementation requires a multidisciplinary team (physicians, nurses, quality improvement officers) and a multifaceted approach (statewide policies),” Dr. Krishna said. “Key stakeholders will need to ‘buy in’ or be willing to support the policy and practice change to ensure its success. To address obstacles, initiatives to support vaginal birth are important, such as provider training on labor and support techniques, criteria for diagnosis of and management of labor dystocia and arrest disorders, standard responses to abnormal fetal heart rate patterns, and availability of expertise to lessen the need for cesarean delivery, such as breech version, instrumented delivery, and twin delivery protocols. It is also important for hospitals to a have a mentor model of quality improvement and shared learning strategies that work.”

Dr. Krishna agreed with the investigators that more work is necessary to determine best strategies for future intervention.

“Research is needed in identifying determinants of success and sustainment,” she said.

Dr. Burke received funding from her employer, Trinity Health, to conduct a pilot study concerning blood loss.

A statewide educational initiative in Maryland was associated with a significant reduction in cesarean delivery rates over 30 months, although program implementation was widely variable across participating hospitals, according to investigators.

Cesarean deliveries dropped 1.6% among nulliparous, term, singleton, vertex births, falling short of the 3.2% reduction recently achieved by a similar program in California, reported lead author Jennifer A. Callaghan-Koru, PhD, of the University of Maryland, Baltimore County, and colleagues.

“Although cesarean delivery can be lifesaving, evidence suggests that there is no benefit to maternal health when national cesarean delivery rates are higher than 20 per 100 live births,” the investigators wrote in Obstetrics & Gynecology.

They noted that cesarean delivery rates in the United States rose dramatically between 1996 and 2006, from 20.7% to 32.9%, before falling back to 31.7% in 2019.

According to the investigators, high cesarean delivery rates have drawn action from a roster of stakeholders, including the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), the Department of Health and Human Services, the Joint Commission, and the Council on Patient Safety in Women’s Health Care.

The latter group created an evidence-based obstetric patient safety bundle that was used in the present study. The investigators recruited 31 out of 32 birthing hospitals in Maryland, and over the course of 30 months, educated the participating hospitals on the practices recommended by the bundle, via in-person and remote training.

To measure implementation and associated outcomes, the investigators used a data portal provided by the ACOG Alliance for Innovation in Maternal Health (AIM) program, which supports adoption of the council’s safety bundle nationwide. Data included number of births; number of cesarean births; overall cesarean delivery rates; cesarean rates among nulliparous, term, singleton, vertex births; cesarean rates among nulliparous, term, singleton, vertex inductions; as well as severe maternal morbidity rates.

Among the 26 safety practices in the bundle, hospitals reported current use of 7 (median) before the program began, with a range from 0 to 23. During the 30-month collaboration, hospitals added a median of 4 practices, ranging from 0 to 17.

Concurrently, cesarean delivery rates for nulliparous, term, singleton, vertex births dropped from 26.9% to 28.5% (P = .011), while rates for inductions dropped to a greater degree, from 36.1% to 31.3% (P less than .001). Further analysis showed that greater reductions in rates of cesarean delivery were associated with adoption of practices in the “Response” domain.

“The Response domain has the largest number of practices that standardize clinical care, including induction scheduling, diagnosis and treatment of labor dystocia and failed induction, and interpretation of fetal heart rate patterns,” the investigators wrote. “The important role of standardizing care is consistent with a Cochrane review that found moderately strong evidence that the implementation of clinical practice guidelines, alongside feedback to clinicians (e.g., second opinions, audit and feedback of rates), can reduce cesarean delivery.”

Dr. Callaghan-Koru and colleagues noted the high variability of implementation among hospitals, which could explain why statewide reductions weren’t more dramatic.

“Other evaluations of perinatal quality improvement collaboratives have also found that some hospitals get left behind in these efforts, without making considerable progress and improving outcomes,” they wrote. “Given that work by state perinatal quality improvement collaboratives represents a primary national strategy for reducing maternal morbidity and mortality, it is critically important to conduct further implementation research to identify determinants of success and strategies to support all participating hospitals to make improvements.”

According to Iris Krishna, MD, of Emory University, Atlanta, each state’s starting point may predict how successful similar programs will be.

“The safe reduction in the cesarean delivery rate will vary by state,” Dr. Krishna said in a written comment. “States that have a well-established perinatal quality collaborative that have the support on the provider, hospital, and statewide level are more likely to successfully implement strategies and see a statistically significant decrease.”

She went on to emphasize the importance of collaboration across multiple levels of organization, and across a variety of health care providers and administrators.

“Successful implementation requires a multidisciplinary team (physicians, nurses, quality improvement officers) and a multifaceted approach (statewide policies),” Dr. Krishna said. “Key stakeholders will need to ‘buy in’ or be willing to support the policy and practice change to ensure its success. To address obstacles, initiatives to support vaginal birth are important, such as provider training on labor and support techniques, criteria for diagnosis of and management of labor dystocia and arrest disorders, standard responses to abnormal fetal heart rate patterns, and availability of expertise to lessen the need for cesarean delivery, such as breech version, instrumented delivery, and twin delivery protocols. It is also important for hospitals to a have a mentor model of quality improvement and shared learning strategies that work.”

Dr. Krishna agreed with the investigators that more work is necessary to determine best strategies for future intervention.

“Research is needed in identifying determinants of success and sustainment,” she said.

Dr. Burke received funding from her employer, Trinity Health, to conduct a pilot study concerning blood loss.