Brandon May

A relatively large number of late-stage pancreatic ductal adenocarcinomas (PDACs) are detected during follow-up surveillance, yet no single patient- or protocol-specific factor appears to be significantly associated with detecting late-stage disease during this period, according to a new systematic literature review and meta-analysis.

The researchers, led by Ankit Chhoda, MD, of Yale University, New Haven, Conn., wrote in Gastroenterology that interval progression in high-risk individuals “highlights the need for improved follow-up methodology with higher accuracy to detect prognostically significant and treatable lesions.”

Individuals at high risk for PDAC are encouraged to undergo routine surveillance for the disease because early detection and resection of T1N0M0 PDAC and high-grade precursors may improve survival outcomes. According to Dr. Chhoda and colleagues, challenges of interval progression of cancers during the surveillance period for gastrointestinal malignancies have been well described in the general and at-risk patient populations. Previous studies, the authors explained, have not scrutinized the issues associated with late-stage PDACs detected during follow-up surveillance.

“Late-stage PDACs necessitate critical appraisal of current follow-up strategies to detect successful targets and perform timely resections,” the authors wrote. The researchers added that the diagnosis of late-stage PDACs during follow-up emphasizes the need for implementing “quality measures to avoid preventable causes, including surveillance adherence and diagnostic errors.”

To understand the incidence rates of late-stage PDACs during follow-up in high-risk individuals, Dr. Chhoda and researchers performed a systematic literature review and meta-analysis of data that included follow-up strategies for early PDAC detection among a high-risk population.

Outcomes of interest for the analysis included the overall diagnosis of advanced neoplasia as well as surveillance-detected/interval late-stage PDACs (T2–4N0M0/metastatic stage PDAC) during follow-up. The investigators defined surveillance-detected and interval late-stage PDACs as late-stage PDACs that were detected during surveillance and as those presenting symptomatically between visits, respectively.

The researchers also performed metaregression of the incidence rates of late-stage PDACs to examine the relationship with clinicoradiologic features in high-risk individuals.

A total of 13 studies on surveillance in 2,169 high-risk individuals were included in the systematic review, while 12 studies were included in the meta-analysis. Across studies, high-risk individuals were followed for over 7,302.72 patient-years for the purposes of detecting incident lesions or progression of preexisting pancreatic abnormalities.

In all high-risk individuals who underwent follow-up, the investigators identified a total yield of advanced neoplasia of 53. This total yield consisted of 7 high-grade pancreatic intraepithelial neoplasms, 7 high-grade intraductal papillary mucinous neoplasms, and 39 PDACs. According to the meta-analysis, the cumulative incidence of advanced neoplasia was 3.3 (95% confidence interval, 0.6-7.4; P < .001) per 1,000 patient-years. During follow-up, the cumulative incidence of surveillance-detected/interval late-stage PDACs was 1.7 per 1,000 patient-years (95% CI, 0.2-4.0; P = .03).

In a separate analysis, the investigators sought to identify the relationship between the modality of follow-up imaging and late-stage PDAC incidence. Imaging modalities used during follow-up were mostly cross-sectional imaging, such as computed tomography or magnetic resonance imaging with cholangiopancreatography (n = 4) or endoscopic ultrasound and cross-sectional modalities (n = 8).

The investigators found no significant associations between late-stage PDACs and surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Incidence of late-stage PDACs in studies with mostly cross-sectional imaging was 0.7 per 1,000 patient-years (95% CI, 0.0-8.0). This incidence rate was lower than that reported with EUS and cross-sectional modalities (2.5 per 1,000 patient-years; 95% CI, 0.6-5.4), but this difference was not statistically significant (P = .2).

No significant difference was found during follow-up in the incidence of late-stage PDACs between high-risk individuals with baseline pancreatic abnormalities (0.0 no significant difference; 95% CI, 0.0-0.3) vs. high-risk individuals with normal baseline (0.9 per 1,000 patient-years; 95% CI, 0.0-2.8) (P = .9).

Most studies included in the analysis did not report on diagnostic errors and surveillance adherence, the researchers wrote. Nonadherence to surveillance as well as delays in surveillance accounted for four late-stage PDACs, and surveillance cessation and/or delays were reported in 4 out of 19 high-risk individuals. There was limited information on symptoms, presentation timing, site of lesion, and surveillance adherence, which the investigators indicated prevented a formal meta-analysis.

In their summary, the study authors noted that in clinical practice there is a need for improved quality measures and adherence to surveillance programs to reduce the risk of diagnostic errors. The authors stated that evidence on the impact of these quality measures “on surveillance outcomes will not only improve quality of surveillance practices, but also enrich our communication with patients who undergo surveillance.”

The researchers reported no conflicts of interest with the pharmaceutical industry, and the study did not receive any funding.

A relatively large number of late-stage pancreatic ductal adenocarcinomas (PDACs) are detected during follow-up surveillance, yet no single patient- or protocol-specific factor appears to be significantly associated with detecting late-stage disease during this period, according to a new systematic literature review and meta-analysis.

The researchers, led by Ankit Chhoda, MD, of Yale University, New Haven, Conn., wrote in Gastroenterology that interval progression in high-risk individuals “highlights the need for improved follow-up methodology with higher accuracy to detect prognostically significant and treatable lesions.”

Individuals at high risk for PDAC are encouraged to undergo routine surveillance for the disease because early detection and resection of T1N0M0 PDAC and high-grade precursors may improve survival outcomes. According to Dr. Chhoda and colleagues, challenges of interval progression of cancers during the surveillance period for gastrointestinal malignancies have been well described in the general and at-risk patient populations. Previous studies, the authors explained, have not scrutinized the issues associated with late-stage PDACs detected during follow-up surveillance.

“Late-stage PDACs necessitate critical appraisal of current follow-up strategies to detect successful targets and perform timely resections,” the authors wrote. The researchers added that the diagnosis of late-stage PDACs during follow-up emphasizes the need for implementing “quality measures to avoid preventable causes, including surveillance adherence and diagnostic errors.”

To understand the incidence rates of late-stage PDACs during follow-up in high-risk individuals, Dr. Chhoda and researchers performed a systematic literature review and meta-analysis of data that included follow-up strategies for early PDAC detection among a high-risk population.

Outcomes of interest for the analysis included the overall diagnosis of advanced neoplasia as well as surveillance-detected/interval late-stage PDACs (T2–4N0M0/metastatic stage PDAC) during follow-up. The investigators defined surveillance-detected and interval late-stage PDACs as late-stage PDACs that were detected during surveillance and as those presenting symptomatically between visits, respectively.

The researchers also performed metaregression of the incidence rates of late-stage PDACs to examine the relationship with clinicoradiologic features in high-risk individuals.

A total of 13 studies on surveillance in 2,169 high-risk individuals were included in the systematic review, while 12 studies were included in the meta-analysis. Across studies, high-risk individuals were followed for over 7,302.72 patient-years for the purposes of detecting incident lesions or progression of preexisting pancreatic abnormalities.

In all high-risk individuals who underwent follow-up, the investigators identified a total yield of advanced neoplasia of 53. This total yield consisted of 7 high-grade pancreatic intraepithelial neoplasms, 7 high-grade intraductal papillary mucinous neoplasms, and 39 PDACs. According to the meta-analysis, the cumulative incidence of advanced neoplasia was 3.3 (95% confidence interval, 0.6-7.4; P < .001) per 1,000 patient-years. During follow-up, the cumulative incidence of surveillance-detected/interval late-stage PDACs was 1.7 per 1,000 patient-years (95% CI, 0.2-4.0; P = .03).

In a separate analysis, the investigators sought to identify the relationship between the modality of follow-up imaging and late-stage PDAC incidence. Imaging modalities used during follow-up were mostly cross-sectional imaging, such as computed tomography or magnetic resonance imaging with cholangiopancreatography (n = 4) or endoscopic ultrasound and cross-sectional modalities (n = 8).

The investigators found no significant associations between late-stage PDACs and surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Incidence of late-stage PDACs in studies with mostly cross-sectional imaging was 0.7 per 1,000 patient-years (95% CI, 0.0-8.0). This incidence rate was lower than that reported with EUS and cross-sectional modalities (2.5 per 1,000 patient-years; 95% CI, 0.6-5.4), but this difference was not statistically significant (P = .2).

No significant difference was found during follow-up in the incidence of late-stage PDACs between high-risk individuals with baseline pancreatic abnormalities (0.0 no significant difference; 95% CI, 0.0-0.3) vs. high-risk individuals with normal baseline (0.9 per 1,000 patient-years; 95% CI, 0.0-2.8) (P = .9).

Most studies included in the analysis did not report on diagnostic errors and surveillance adherence, the researchers wrote. Nonadherence to surveillance as well as delays in surveillance accounted for four late-stage PDACs, and surveillance cessation and/or delays were reported in 4 out of 19 high-risk individuals. There was limited information on symptoms, presentation timing, site of lesion, and surveillance adherence, which the investigators indicated prevented a formal meta-analysis.

In their summary, the study authors noted that in clinical practice there is a need for improved quality measures and adherence to surveillance programs to reduce the risk of diagnostic errors. The authors stated that evidence on the impact of these quality measures “on surveillance outcomes will not only improve quality of surveillance practices, but also enrich our communication with patients who undergo surveillance.”

The researchers reported no conflicts of interest with the pharmaceutical industry, and the study did not receive any funding.

A relatively large number of late-stage pancreatic ductal adenocarcinomas (PDACs) are detected during follow-up surveillance, yet no single patient- or protocol-specific factor appears to be significantly associated with detecting late-stage disease during this period, according to a new systematic literature review and meta-analysis.

The researchers, led by Ankit Chhoda, MD, of Yale University, New Haven, Conn., wrote in Gastroenterology that interval progression in high-risk individuals “highlights the need for improved follow-up methodology with higher accuracy to detect prognostically significant and treatable lesions.”

Individuals at high risk for PDAC are encouraged to undergo routine surveillance for the disease because early detection and resection of T1N0M0 PDAC and high-grade precursors may improve survival outcomes. According to Dr. Chhoda and colleagues, challenges of interval progression of cancers during the surveillance period for gastrointestinal malignancies have been well described in the general and at-risk patient populations. Previous studies, the authors explained, have not scrutinized the issues associated with late-stage PDACs detected during follow-up surveillance.

“Late-stage PDACs necessitate critical appraisal of current follow-up strategies to detect successful targets and perform timely resections,” the authors wrote. The researchers added that the diagnosis of late-stage PDACs during follow-up emphasizes the need for implementing “quality measures to avoid preventable causes, including surveillance adherence and diagnostic errors.”

To understand the incidence rates of late-stage PDACs during follow-up in high-risk individuals, Dr. Chhoda and researchers performed a systematic literature review and meta-analysis of data that included follow-up strategies for early PDAC detection among a high-risk population.

Outcomes of interest for the analysis included the overall diagnosis of advanced neoplasia as well as surveillance-detected/interval late-stage PDACs (T2–4N0M0/metastatic stage PDAC) during follow-up. The investigators defined surveillance-detected and interval late-stage PDACs as late-stage PDACs that were detected during surveillance and as those presenting symptomatically between visits, respectively.

The researchers also performed metaregression of the incidence rates of late-stage PDACs to examine the relationship with clinicoradiologic features in high-risk individuals.

A total of 13 studies on surveillance in 2,169 high-risk individuals were included in the systematic review, while 12 studies were included in the meta-analysis. Across studies, high-risk individuals were followed for over 7,302.72 patient-years for the purposes of detecting incident lesions or progression of preexisting pancreatic abnormalities.

In all high-risk individuals who underwent follow-up, the investigators identified a total yield of advanced neoplasia of 53. This total yield consisted of 7 high-grade pancreatic intraepithelial neoplasms, 7 high-grade intraductal papillary mucinous neoplasms, and 39 PDACs. According to the meta-analysis, the cumulative incidence of advanced neoplasia was 3.3 (95% confidence interval, 0.6-7.4; P < .001) per 1,000 patient-years. During follow-up, the cumulative incidence of surveillance-detected/interval late-stage PDACs was 1.7 per 1,000 patient-years (95% CI, 0.2-4.0; P = .03).

In a separate analysis, the investigators sought to identify the relationship between the modality of follow-up imaging and late-stage PDAC incidence. Imaging modalities used during follow-up were mostly cross-sectional imaging, such as computed tomography or magnetic resonance imaging with cholangiopancreatography (n = 4) or endoscopic ultrasound and cross-sectional modalities (n = 8).

The investigators found no significant associations between late-stage PDACs and surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Incidence of late-stage PDACs in studies with mostly cross-sectional imaging was 0.7 per 1,000 patient-years (95% CI, 0.0-8.0). This incidence rate was lower than that reported with EUS and cross-sectional modalities (2.5 per 1,000 patient-years; 95% CI, 0.6-5.4), but this difference was not statistically significant (P = .2).

No significant difference was found during follow-up in the incidence of late-stage PDACs between high-risk individuals with baseline pancreatic abnormalities (0.0 no significant difference; 95% CI, 0.0-0.3) vs. high-risk individuals with normal baseline (0.9 per 1,000 patient-years; 95% CI, 0.0-2.8) (P = .9).

Most studies included in the analysis did not report on diagnostic errors and surveillance adherence, the researchers wrote. Nonadherence to surveillance as well as delays in surveillance accounted for four late-stage PDACs, and surveillance cessation and/or delays were reported in 4 out of 19 high-risk individuals. There was limited information on symptoms, presentation timing, site of lesion, and surveillance adherence, which the investigators indicated prevented a formal meta-analysis.

In their summary, the study authors noted that in clinical practice there is a need for improved quality measures and adherence to surveillance programs to reduce the risk of diagnostic errors. The authors stated that evidence on the impact of these quality measures “on surveillance outcomes will not only improve quality of surveillance practices, but also enrich our communication with patients who undergo surveillance.”

The researchers reported no conflicts of interest with the pharmaceutical industry, and the study did not receive any funding.

The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*

Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.

In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.

Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.

Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.

Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).

Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.

In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.

Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.

In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.

Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.

“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”

Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.

Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.

This article was updated 1/11/22. 

*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.

The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*

Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.

In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.

Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.

Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.

Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).

Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.

In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.

Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.

In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.

Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.

“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”

Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.

Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.

This article was updated 1/11/22. 

*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.

The recently developed ACE index – which incorporates three variables at hospital admission (C-reactive protein [CRP], albumin, and endoscopic severity) – accurately predicts steroid response at hospital admission in patients with acute severe ulcerative colitis (ASUC). This is according to study findings presented at the annual Advances in Inflammatory Bowel Diseases conference by Marta Freitas, MD, of the Senhora da Oliveira Hospital in Guimarães, Portugal.*

Although intravenous steroids represent the first-line medical therapy for patients admitted to the hospital with acute UC, one study found that approximately 30% of patients with ASUC do not respond to this treatment approach and therefore require more advanced management options.

In patients with ASUC, delays in initiating therapy may be associated with an increased risk of mortality, explained Dr. Freitas and colleagues. Given this risk, there is a need for sensitive and accurate tools that can identify patients at admission who are at high risk of steroid nonresponse and who may likewise receive benefit from surgical intervention or earlier second-line therapy.

Early prediction of response to steroids in patients with ASUC at time of admission could also be helpful for prioritizing further assessment and counseling. The ACE index was recently developed to identify these patients to help improve risk stratification and facilitate earlier treatment delivery. A combination of three parameters is found within the ACE index: albumin ≤30 g/L; CRP ≥50 mg/L; and increased endoscopic severity as defined by a Mayo endoscopic score of 3.

Dr. Freitas and researchers retrospectively evaluated the performance of the ACE index in predicting steroid response in 65 patients with ASUC (mean age, 34 years). The study included a review of admissions for the disease between 2005 and 2020. The accuracy of the ACE index score was evaluated through the area under the curve.

Approximately 78.5% of patients in the retrospective cohort study had responded to steroids. Compared with nonresponders, responders had significantly different mean CRP (108.0 ± 60.0 vs. 66.0 ± 53.2 mg/dL, respectively; P = .01), mean albumin (2.9 ± 0.66 vs. 3.4 ± 0.71 g/L; P = .02), and median endoscopic severity score (3 vs. 3; interquartile range, 1 vs. 0; P = .005) at admission. In contrast, no statistically significant difference was found between responders versus nonresponders in regard to the median UC Endoscopic Index of Severity (UCEIS) score (8 vs. 7; P = .28).

Overall, the median ACE index score was 2. Steroid nonresponders had a significantly higher ACE index score (2.5 vs. 1; P = .001). The researchers noted that the ACE index score was a significant predictor of steroid response (AUC, 0.789; P = .001). Half (50.0%) of patients with an ACE index score of 3 had no response to steroids, while 86.3% of patients who had an ACE index score lower than 3 experienced a steroid response.

In a poster presentation by Hartman Brunt, MD, of the Louisiana State University Health Sciences Center in Baton Rouge, real-world data suggest there exists several inconsistencies in the use of UC-monitoring strategies recommended by clinical practice guidelines. According to a single-center retrospective chart review of adult patients with moderate to severe UC, Dr. Brunt and colleagues found that measurement of CRP decreased over time as did measurement of fecal calprotectin.

Given the lack of standardization for IBD monitoring, Dr. Hartman and colleagues noted “there is inevitably increased variability in provider care.” Consequently, this variability and lack of guideline adherence may lead to heterogeneous effects among the IBD patient population, including those that may drive suboptimal long-term outcomes.

In addition to disease monitoring, assessment of treatment response remains highly valuable, yet no clinical guidance currently exists on the use of the ACE index score in ASUC. Further research is needed to determine the validity of the ACE Index in a larger patient population to inform future clinical practice guidelines and expert consensus statements.

Ashwin Ananthakrishnan, MBBS, a gastroenterologist from Massachusetts General Hospital in Boston, said in an email to this news organization that there is an urgent need for tools that “accurately predict treatment response in severe UC because of the higher morbidity and rate of surgery in this population.” Dr. Ananthakrishnan is a co–primary investigator of the MASCC (Multi-center Acute Severe UC Cohort Study), sponsored by Johns Hopkins University, which is investigating the ACE index and other predictors of outcomes in severe UC.

“In addition, treatment decisions need to be made fairly quickly as clinical condition may change day to day,” further emphasizing the need for these predictors, added Dr. Ananthakrishnan. “At this point, the ACE index and other prediction scores have been described from observational studies, but the key is to prospectively incorporate this into a treatment algorithm.”

Dr. Ananthakrishnan explained that patients with a high ACE index, or those with UC who satisfy the high-risk criteria of other prediction models, may benefit from early or even upfront rescue therapy rather than trying steroids for 3-5 days first. He added that “the field is not quite there, and we need more study of this” approach.

Dr. Freitas, Dr. Brunt, and Dr. Ananthakrishnan declared no relevant conflicts of interest.

This article was updated 1/11/22. 

*Correction, 1/11/22: An earlier version of this article misstated Dr. Martha Freitas' name.

A real-world analysis of tofacitinib, presented at the annual Advances in Inflammatory Bowel Disease conference, confirms that long-term use of the selective immunosuppressant agent tofacitinib is associated with high rates of steroid-free remission in patients with ulcerative colitis (UC). These findings, along with clinical practice observations made during another session at the conference, further validate the efficacy of tofacitinib beyond that currently reported in specific clinical trial populations.

Tofacitinib is a small-molecule Janus kinase inhibitor that interferes with the intracellular JAK/signal transducer and activators of transcription pathway. Compared with other biologic agents, tofacitinib simultaneously acts on several cytokines and exerts broader effects on gastrointestinal inflammation.

Tofacitinib’s approval for moderate to severe UC was based on data from the OCTAVE clinical trial program. Although the phase 3 OCTAVE trial showed the JAK inhibitor features dose-dependent efficacy in inducing and maintaining remission in UC, stringent inclusion and exclusion criteria limit the generalizability of the trial’s findings across the broader, real-world UC population.

Findings from the recent analysis on tofacitinib were presented at AIBD 2021 by Knyazev Oleg, MD, who is the head of department of inflammatory bowel diseases at A.S. Loginov Moscow Clinical Scientific and Practical Center.

Dr. Oleg and colleagues reported on real-world treatment observations of 58 tofacitinib-treated patients with UC. Treatment efficacy was evaluated using the Mayo index (score <2), erythrocyte sedimentation rate, C-reactive protein, hemoglobin, fecal calprotectin, and the need for glucocorticoids (GCS).

At the time of tofacitinib initiation, all patients received GCS, with a mean therapeutic dose of 40 mg. In all 49 patients who responded to therapy, corticosteroids were discontinued after induction.

Only 15.5% (n = 9) of the study cohort did not respond to the JAK inhibitor during the follow-up period. A total of 14 patients (24.1%) who previously received anti-TNF therapies required a prolonged induction course of 20 mg tofacitinib. More than one out of five patients (22.4%) required repeated corticosteroids to manage exacerbations or dwindled tofacitinib response.

During another session, which discussed prescription treatment for moderate to severe UC, Bincy Abraham, MD, a professor of clinical medicine at Houston Methodist Academic Institute, summarized currently available clinical trial data on tofacitinib and discussed her own observations in her practice regarding the efficacy of the JAK inhibitor in the UC population.

The current data show the oral JAK inhibitor allows patients to reach remission as early as 8 weeks, with corresponding reductions observed in rectal bleeding and stool frequency as early as 2 weeks after therapy initiation. While the efficacy findings are corroborated by her own clinical practice, Dr. Abraham largely discussed the safety implications of the treatment.

Dr. Abraham emphasized the need for risk-mitigation strategies before initiating tofacitinib in appropriately selected patients with UC. In particular, Dr. Abraham explained that clinicians should be alerted to the possibility of tuberculosis as an opportunistic infection in tofacitinib-treated patients. “Before starting, I always liked to make sure that patients are getting checked for tuberculosis,” she said, adding that she performs annual monitoring for patients treated with the agent.

When considering tofacitinib, Dr. Abraham added that clinicians should ultimately consider discussing the risks of therapy versus the benefits in eligible patients.

During the question-and-answer portion of her session, Dr. Abraham noted that she has observed mixed findings in regard to tofacitinib’s effects on lipid levels. Specifically, only a small number of patients with UC in her practice have had to initiate cholesterol therapy while taking tofacitinib, but these patients typically have high-risk factors for hyperlipidemia, including family history and elevated body mass index.

On a question regarding the risk of shingles, Dr. Abraham noted that, if a patient does indeed develop the condition while taking tofacitinib, the therapy should be halted until shingles is resolved. In her practice, Dr. Abraham explained shingles vaccination is a priority before starting tofacitinib, suggesting this strategy has thus far prevented her tofacitinib-treated patients from developing the condition.

In patients with flares, Dr. Abraham noted that “we don’t have any specific clinical trial data specifically looking at” how to manage tofacitinib doses to further manage difficult-to-treat disease. She stated that, in her practice, she increases the dose of tofacitinib in patients who experience flares, as this often improves response. Subsequent dose reductions should be based on an individualized basis, with many patients requiring higher doses at varying periods.

Dr. Oleg has no relevant financial disclosures. Dr. Abraham reported conflicts of interest with Pfizer, which sponsored her discussion.
 

A real-world analysis of tofacitinib, presented at the annual Advances in Inflammatory Bowel Disease conference, confirms that long-term use of the selective immunosuppressant agent tofacitinib is associated with high rates of steroid-free remission in patients with ulcerative colitis (UC). These findings, along with clinical practice observations made during another session at the conference, further validate the efficacy of tofacitinib beyond that currently reported in specific clinical trial populations.

Tofacitinib is a small-molecule Janus kinase inhibitor that interferes with the intracellular JAK/signal transducer and activators of transcription pathway. Compared with other biologic agents, tofacitinib simultaneously acts on several cytokines and exerts broader effects on gastrointestinal inflammation.

Tofacitinib’s approval for moderate to severe UC was based on data from the OCTAVE clinical trial program. Although the phase 3 OCTAVE trial showed the JAK inhibitor features dose-dependent efficacy in inducing and maintaining remission in UC, stringent inclusion and exclusion criteria limit the generalizability of the trial’s findings across the broader, real-world UC population.

Findings from the recent analysis on tofacitinib were presented at AIBD 2021 by Knyazev Oleg, MD, who is the head of department of inflammatory bowel diseases at A.S. Loginov Moscow Clinical Scientific and Practical Center.

Dr. Oleg and colleagues reported on real-world treatment observations of 58 tofacitinib-treated patients with UC. Treatment efficacy was evaluated using the Mayo index (score <2), erythrocyte sedimentation rate, C-reactive protein, hemoglobin, fecal calprotectin, and the need for glucocorticoids (GCS).

At the time of tofacitinib initiation, all patients received GCS, with a mean therapeutic dose of 40 mg. In all 49 patients who responded to therapy, corticosteroids were discontinued after induction.

Only 15.5% (n = 9) of the study cohort did not respond to the JAK inhibitor during the follow-up period. A total of 14 patients (24.1%) who previously received anti-TNF therapies required a prolonged induction course of 20 mg tofacitinib. More than one out of five patients (22.4%) required repeated corticosteroids to manage exacerbations or dwindled tofacitinib response.

During another session, which discussed prescription treatment for moderate to severe UC, Bincy Abraham, MD, a professor of clinical medicine at Houston Methodist Academic Institute, summarized currently available clinical trial data on tofacitinib and discussed her own observations in her practice regarding the efficacy of the JAK inhibitor in the UC population.

The current data show the oral JAK inhibitor allows patients to reach remission as early as 8 weeks, with corresponding reductions observed in rectal bleeding and stool frequency as early as 2 weeks after therapy initiation. While the efficacy findings are corroborated by her own clinical practice, Dr. Abraham largely discussed the safety implications of the treatment.

Dr. Abraham emphasized the need for risk-mitigation strategies before initiating tofacitinib in appropriately selected patients with UC. In particular, Dr. Abraham explained that clinicians should be alerted to the possibility of tuberculosis as an opportunistic infection in tofacitinib-treated patients. “Before starting, I always liked to make sure that patients are getting checked for tuberculosis,” she said, adding that she performs annual monitoring for patients treated with the agent.

When considering tofacitinib, Dr. Abraham added that clinicians should ultimately consider discussing the risks of therapy versus the benefits in eligible patients.

During the question-and-answer portion of her session, Dr. Abraham noted that she has observed mixed findings in regard to tofacitinib’s effects on lipid levels. Specifically, only a small number of patients with UC in her practice have had to initiate cholesterol therapy while taking tofacitinib, but these patients typically have high-risk factors for hyperlipidemia, including family history and elevated body mass index.

On a question regarding the risk of shingles, Dr. Abraham noted that, if a patient does indeed develop the condition while taking tofacitinib, the therapy should be halted until shingles is resolved. In her practice, Dr. Abraham explained shingles vaccination is a priority before starting tofacitinib, suggesting this strategy has thus far prevented her tofacitinib-treated patients from developing the condition.

In patients with flares, Dr. Abraham noted that “we don’t have any specific clinical trial data specifically looking at” how to manage tofacitinib doses to further manage difficult-to-treat disease. She stated that, in her practice, she increases the dose of tofacitinib in patients who experience flares, as this often improves response. Subsequent dose reductions should be based on an individualized basis, with many patients requiring higher doses at varying periods.

Dr. Oleg has no relevant financial disclosures. Dr. Abraham reported conflicts of interest with Pfizer, which sponsored her discussion.
 

A real-world analysis of tofacitinib, presented at the annual Advances in Inflammatory Bowel Disease conference, confirms that long-term use of the selective immunosuppressant agent tofacitinib is associated with high rates of steroid-free remission in patients with ulcerative colitis (UC). These findings, along with clinical practice observations made during another session at the conference, further validate the efficacy of tofacitinib beyond that currently reported in specific clinical trial populations.

Tofacitinib is a small-molecule Janus kinase inhibitor that interferes with the intracellular JAK/signal transducer and activators of transcription pathway. Compared with other biologic agents, tofacitinib simultaneously acts on several cytokines and exerts broader effects on gastrointestinal inflammation.

Tofacitinib’s approval for moderate to severe UC was based on data from the OCTAVE clinical trial program. Although the phase 3 OCTAVE trial showed the JAK inhibitor features dose-dependent efficacy in inducing and maintaining remission in UC, stringent inclusion and exclusion criteria limit the generalizability of the trial’s findings across the broader, real-world UC population.

Findings from the recent analysis on tofacitinib were presented at AIBD 2021 by Knyazev Oleg, MD, who is the head of department of inflammatory bowel diseases at A.S. Loginov Moscow Clinical Scientific and Practical Center.

Dr. Oleg and colleagues reported on real-world treatment observations of 58 tofacitinib-treated patients with UC. Treatment efficacy was evaluated using the Mayo index (score <2), erythrocyte sedimentation rate, C-reactive protein, hemoglobin, fecal calprotectin, and the need for glucocorticoids (GCS).

At the time of tofacitinib initiation, all patients received GCS, with a mean therapeutic dose of 40 mg. In all 49 patients who responded to therapy, corticosteroids were discontinued after induction.

Only 15.5% (n = 9) of the study cohort did not respond to the JAK inhibitor during the follow-up period. A total of 14 patients (24.1%) who previously received anti-TNF therapies required a prolonged induction course of 20 mg tofacitinib. More than one out of five patients (22.4%) required repeated corticosteroids to manage exacerbations or dwindled tofacitinib response.

During another session, which discussed prescription treatment for moderate to severe UC, Bincy Abraham, MD, a professor of clinical medicine at Houston Methodist Academic Institute, summarized currently available clinical trial data on tofacitinib and discussed her own observations in her practice regarding the efficacy of the JAK inhibitor in the UC population.

The current data show the oral JAK inhibitor allows patients to reach remission as early as 8 weeks, with corresponding reductions observed in rectal bleeding and stool frequency as early as 2 weeks after therapy initiation. While the efficacy findings are corroborated by her own clinical practice, Dr. Abraham largely discussed the safety implications of the treatment.

Dr. Abraham emphasized the need for risk-mitigation strategies before initiating tofacitinib in appropriately selected patients with UC. In particular, Dr. Abraham explained that clinicians should be alerted to the possibility of tuberculosis as an opportunistic infection in tofacitinib-treated patients. “Before starting, I always liked to make sure that patients are getting checked for tuberculosis,” she said, adding that she performs annual monitoring for patients treated with the agent.

When considering tofacitinib, Dr. Abraham added that clinicians should ultimately consider discussing the risks of therapy versus the benefits in eligible patients.

During the question-and-answer portion of her session, Dr. Abraham noted that she has observed mixed findings in regard to tofacitinib’s effects on lipid levels. Specifically, only a small number of patients with UC in her practice have had to initiate cholesterol therapy while taking tofacitinib, but these patients typically have high-risk factors for hyperlipidemia, including family history and elevated body mass index.

On a question regarding the risk of shingles, Dr. Abraham noted that, if a patient does indeed develop the condition while taking tofacitinib, the therapy should be halted until shingles is resolved. In her practice, Dr. Abraham explained shingles vaccination is a priority before starting tofacitinib, suggesting this strategy has thus far prevented her tofacitinib-treated patients from developing the condition.

In patients with flares, Dr. Abraham noted that “we don’t have any specific clinical trial data specifically looking at” how to manage tofacitinib doses to further manage difficult-to-treat disease. She stated that, in her practice, she increases the dose of tofacitinib in patients who experience flares, as this often improves response. Subsequent dose reductions should be based on an individualized basis, with many patients requiring higher doses at varying periods.

Dr. Oleg has no relevant financial disclosures. Dr. Abraham reported conflicts of interest with Pfizer, which sponsored her discussion.
 

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff .

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff .

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff .

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is also an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

This article was updated on Jan. 3, 2022.

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is also an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

This article was updated on Jan. 3, 2022.

Vedolizumab does not seem to increase the risk of Clostridioides difficile infection (CDI), compared with anti–tumor necrosis factor (TNF) therapies in biologic-naive patients with ulcerative colitis (UC), despite concerns that the gut-selective monoclonal antibody treatment may increase gastrointestinal infections at a greater rate than other biologics in this patient population.

Perturbations of the gut microbiota that occur in IBD predispose patients to CDI. Given that treatment with monoclonal antibody vedolizumab exerts an inhibitory action on lymphocyte trafficking to the intestines, questions have been raised on whether this action could increase the risk of CDI in an already vulnerable population.

In patients with UC, the incidence of CDI typically confers a higher risk of adverse outcomes. Unfortunately, CDI is a common complication associated with inflammatory bowel disease (IBD) that can lead to disease flares, further adding to the physical and psychological burden associated with the condition, according to recent studies.

These concerns, however, may not be warranted in patients with UC, according to findings from a retrospective study presented at the annual Advances in Inflammatory Bowel Diseases conference by Rahul Dalal, MD, a gastroenterology fellow at Brigham and Women’s Hospital in Boston.

In the study, Dr. Dalal and colleagues retrospectively analyzed electronic medical records of adult patients with UC who initiated infliximab, adalimumab, or vedolizumab between June 2014 and December 2020. Patients in this retrospective cohort were followed until there was a documented occurrence of CDI, colectomy, or biologic discontinuation/switch, or until the last recorded gastroenterology encounter.

The researchers analyzed the time from biologic initiation to first CDI, which was characterized by a positive stool for C. difficile toxin or toxigenic C. difficile polymerase chain reaction with CDI-specific antibiotic prescriptions. Additionally, the investigators evaluated rates of CDI-related hospitalization, colectomy, or death within a 30-day period of CDI. The primary analysis compared patients with UC who initiated vedolizumab (n = 195) versus anti-TNF therapy (n = 610).

Compared with those treated with anti-TNF agents, patients who initiated vedolizumab were older and less frequently received systemic corticosteroids or had UC-related hospitalization within 12 months prior to starting biologics.

Over 1,436 patient-years’ worth of follow-up, the investigators observed 43 CDIs. Patients treated with vedolizumab less frequently had CDI (1.0% vs. 6.7%; P =.001) and CDI hospitalization (1.0% vs. 3.8%; P =.042), compared with those treated with anti-TNF therapies. The investigators reported no significant differences in the rates of colectomies or deaths or rates of exposure to antibiotics/corticosteroids during the follow-up period or within 30 days prior to CDI onset.

In the unadjusted Cox model, the researchers reported that vedolizumab featured a lower hazard of CDI, compared with anti-TNF (hazard ratio, 0.17; 95% confidence interval, 0.04-0.71). The multivariable Cox model found no significant difference in hazard of CDI for vedolizumab when compared with anti-TNF therapy (HR, 0.33; 95% CI, 0.05-2.03) or immunomodulator exposure (HR, 1.01; 95% CI, 0.41-2.40). The incidence of CDI prior to biologic initiation was associated with an increased hazard of subsequent CDI (HR, 5.95; 95% CI, 2.93-12.09). In the subgroup of patients who experienced a CDI, approximately 39.5% had CDI before biologic initiation at a median of 227 days preceding the subsequent event.

“Vedolizumab is one of the safest biologics that we have in the clinic,” said Jean-Frederic Colombel, MD, who was asked to comment on the study. Dr. Colombel, who wasn’t involved in the study, is a gastroenterologist and serves as director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai, both in New York. “Findings from this study reinforce the safety profile of vedolizumab” despite the potential concerns regarding gastroenterological infection with the agent, he added.
 

Recurrence worries

Recurrent CDI is also an issue in patients with IBD, many of whom are considered at high risk for initial and recurrent infection. During a session on CDI and recurrence at the AIBD meeting, Sahil Khanna, MBBS, of the Mayo Clinic, explained that there are three different treatment guidelines to manage initial CDI in patients with IBD.

Predominantly, these guidelines also suggest human monoclonal antibody bezlotoxumab could be used for prevention of CDI recurrence in patients at high risk of recurrence, including those who had experienced severe CDI. “One can argue that anyone with IBD who has C. difficile can be a severe CDI patient because of the bad outcomes we can see,” he explained.

“We do know that IBD is a state of chronic microbial dysbiosis compared to our patients without IBD who get C. difficile because of antibiotic exposure, and that’s why these patients have a high risk of recurrence, compared with non-IBD patients,” said Dr. Khanna. He noted that the bezlotoxumab studies showed numerically lower CDI recurrence rates compared with other treatments in patients with IBD who were initially treated with the monoclonal antibody, but this difference was not statistically significant. “But again, this agent has been shown to be safe in this patient population.”

Dr. Dalal reported having no relevant conflicts of interest. Dr. Colombel has consulted for Takeda, which markets Entyvio for UC. Dr. Khanna has research grants from Rebiotix, as well as consulting fees from Shire Plc, Premier, Facile Therapeutics, and ProbioTech.

This article was updated on Jan. 3, 2022.

Real-world practice data show that less than 10% of patients with inflammatory bowel disease (IBD) receive early treatment with monoclonal antibody vedolizumab, despite better outcomes with earlier initiation. That said, earlier initiation of vedolizumab appears to be more common in younger patients and women, according to the study findings.

Previous research supports the early use of biologics in the management of IBD, given findings that show earlier treatment is associated with increased likelihood of response and remission compared with delayed management. In actual clinical practice, biologic agents are often delayed, potentially contributing to suboptimal outcomes and increased risks of IBD-associated adverse effects.

In a real-world study presented during the 2021 Advances in Inflammatory Bowel Diseases (AIBD) meeting by Maja Kuharic, a PhD candidate at the University of Illinois at Chicago, researchers assessed administrative datasets to gauge the timing of vedolizumab utilization in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC).

Data from the 2017 to 2019 MarketScan commercial and Medicare claims databases were examined in the study. Patients with continuous enrollment in the same health plan for 12 months or longer both before and after their initial IBD diagnosis were included. Additionally, the analysis included patients with 1 or more vedolizumab claim following the index IBD diagnosis.

A total of five treatment pathways were predefined for the study. First, early vedolizumab use was defined as treatment with the monoclonal antibody therapy within 30 days of the first IBD diagnostic claim. A “delayed vedolizumab 1” initiation group was defined as initial treatment with immunomodulators followed by switching to vedolizumab. Additionally, “delayed vedolizumab 2” was defined by initial utilization of corticosteroids with immunomodulators prior to vedolizumab initiation. “Delayed vedolizumab 3” was characterized by the initial use of 5-aminosalicylic acid (5-ASA) with corticosteroids before vedolizumab. Finally, “delayed vedolizumab 4” was defined by the use of 5-ASA with corticosteroids and immunomodulators before vedolizumab.

The real-world cohort study included 1,342 patients with UC (median age, 43 years; 51.0% male) and 964 patients with CD (median age, 45 years; 43.6% male) who received vedolizumab. Early vedolizumab initiation was observed in 6.6% of patients with UC and 9.6% of patients with CD. In the UC population, the proportions of patients classified in the delayed vedolizumab 1, 2, 3, and 4 groups were 7.5%, 14.8%, 37.6%, and 33.4%, respectively. Among the CD group, the proportions of patients in each delayed vedolizumab arms were 19.0%, 36.8%, 19.0%, and 15.6%, respectively.

In the UC cohort, patients who experienced early vedolizumab initiation had a median younger age than those in the delayed groups (40 vs. 44 years, respectively). Additionally, the proportion of men was lower in the early vedolizumab cohort (46.1% vs. 51.4%). Similar findings were observed in the CD group: those who initiated vedolizumab earlier had a lower median age (43 vs. 45 years) and were less frequently men (39.8%% vs. 43.9%).

Across both treatment indications, there were no clinically meaningful differences between treatment groups in terms of geographic location, payer type (that is, commercial vs. Medicare), or year of diagnosis.

According to Jean-Frederic Colombel, MD, who was asked to comment on the study, a limitation of the findings is the lack of explanation as to why early initiation of vedolizumab is higher in younger patients and women. “Rather, it just reflects clinical practice in the real world with no justification,” said Dr. Colombel, a gastroenterologist and director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai in New York, who wasn’t involved in the study.

“[The findings] may look surprising since the drug, because of its safety, could be considered first-line in elderly fragile patients with higher risk of infection,” added Dr. Colombel. He noted that what is missing from the study is the longitudinal assessment of early treatment in terms of disease modification. In particular, he asked, what needs to be further explored is the “long-term impact of early vedolizumab initiation on the risk of surgery and complications.”

During another session at the AIBD 2021 meeting on the positioning of therapies in IBD, Anita Afzali, MD, of the Ohio State University Wexner Medical Center in Hilliard, Ohio, noted that for newly diagnosed patients, early initiation of vedolizumab may be most appropriate for patients with unfavorable pharmacokinetics. For instance, Dr. Afzali said, vedolizumab or ustekinumab could be the biologics of choice for an older woman with ileocolonic CD and the HLA-DQA1*04 genotype in whom clinicians would want to avoid an immunomodulator.

“When you look at different factors, whether you’re discussing the drug itself or the patient, there’s different considerations” for selecting a therapy in IBD, explained Dr. Afzali. These considerations, she stated, include those related to drug efficacy and safety as well as disease and individual characteristics such as age, comorbidities, preferences, and costs.

Ms. Kuharic is a PhD candidate and is also a Health Economics and Outcomes Research Fellow at Takeda. Dr. Colombel has consulted for Takeda, which markets vedolizumab for CD and UC. Dr. Afzali has reported relationships with several pharmaceutical companies, including BMS, Eli Lilly, Gilead, Pfizer, IBD Horizons, AbbVie, Takeda, and Janssen.

Real-world practice data show that less than 10% of patients with inflammatory bowel disease (IBD) receive early treatment with monoclonal antibody vedolizumab, despite better outcomes with earlier initiation. That said, earlier initiation of vedolizumab appears to be more common in younger patients and women, according to the study findings.

Previous research supports the early use of biologics in the management of IBD, given findings that show earlier treatment is associated with increased likelihood of response and remission compared with delayed management. In actual clinical practice, biologic agents are often delayed, potentially contributing to suboptimal outcomes and increased risks of IBD-associated adverse effects.

In a real-world study presented during the 2021 Advances in Inflammatory Bowel Diseases (AIBD) meeting by Maja Kuharic, a PhD candidate at the University of Illinois at Chicago, researchers assessed administrative datasets to gauge the timing of vedolizumab utilization in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC).

Data from the 2017 to 2019 MarketScan commercial and Medicare claims databases were examined in the study. Patients with continuous enrollment in the same health plan for 12 months or longer both before and after their initial IBD diagnosis were included. Additionally, the analysis included patients with 1 or more vedolizumab claim following the index IBD diagnosis.

A total of five treatment pathways were predefined for the study. First, early vedolizumab use was defined as treatment with the monoclonal antibody therapy within 30 days of the first IBD diagnostic claim. A “delayed vedolizumab 1” initiation group was defined as initial treatment with immunomodulators followed by switching to vedolizumab. Additionally, “delayed vedolizumab 2” was defined by initial utilization of corticosteroids with immunomodulators prior to vedolizumab initiation. “Delayed vedolizumab 3” was characterized by the initial use of 5-aminosalicylic acid (5-ASA) with corticosteroids before vedolizumab. Finally, “delayed vedolizumab 4” was defined by the use of 5-ASA with corticosteroids and immunomodulators before vedolizumab.

The real-world cohort study included 1,342 patients with UC (median age, 43 years; 51.0% male) and 964 patients with CD (median age, 45 years; 43.6% male) who received vedolizumab. Early vedolizumab initiation was observed in 6.6% of patients with UC and 9.6% of patients with CD. In the UC population, the proportions of patients classified in the delayed vedolizumab 1, 2, 3, and 4 groups were 7.5%, 14.8%, 37.6%, and 33.4%, respectively. Among the CD group, the proportions of patients in each delayed vedolizumab arms were 19.0%, 36.8%, 19.0%, and 15.6%, respectively.

In the UC cohort, patients who experienced early vedolizumab initiation had a median younger age than those in the delayed groups (40 vs. 44 years, respectively). Additionally, the proportion of men was lower in the early vedolizumab cohort (46.1% vs. 51.4%). Similar findings were observed in the CD group: those who initiated vedolizumab earlier had a lower median age (43 vs. 45 years) and were less frequently men (39.8%% vs. 43.9%).

Across both treatment indications, there were no clinically meaningful differences between treatment groups in terms of geographic location, payer type (that is, commercial vs. Medicare), or year of diagnosis.

According to Jean-Frederic Colombel, MD, who was asked to comment on the study, a limitation of the findings is the lack of explanation as to why early initiation of vedolizumab is higher in younger patients and women. “Rather, it just reflects clinical practice in the real world with no justification,” said Dr. Colombel, a gastroenterologist and director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai in New York, who wasn’t involved in the study.

“[The findings] may look surprising since the drug, because of its safety, could be considered first-line in elderly fragile patients with higher risk of infection,” added Dr. Colombel. He noted that what is missing from the study is the longitudinal assessment of early treatment in terms of disease modification. In particular, he asked, what needs to be further explored is the “long-term impact of early vedolizumab initiation on the risk of surgery and complications.”

During another session at the AIBD 2021 meeting on the positioning of therapies in IBD, Anita Afzali, MD, of the Ohio State University Wexner Medical Center in Hilliard, Ohio, noted that for newly diagnosed patients, early initiation of vedolizumab may be most appropriate for patients with unfavorable pharmacokinetics. For instance, Dr. Afzali said, vedolizumab or ustekinumab could be the biologics of choice for an older woman with ileocolonic CD and the HLA-DQA1*04 genotype in whom clinicians would want to avoid an immunomodulator.

“When you look at different factors, whether you’re discussing the drug itself or the patient, there’s different considerations” for selecting a therapy in IBD, explained Dr. Afzali. These considerations, she stated, include those related to drug efficacy and safety as well as disease and individual characteristics such as age, comorbidities, preferences, and costs.

Ms. Kuharic is a PhD candidate and is also a Health Economics and Outcomes Research Fellow at Takeda. Dr. Colombel has consulted for Takeda, which markets vedolizumab for CD and UC. Dr. Afzali has reported relationships with several pharmaceutical companies, including BMS, Eli Lilly, Gilead, Pfizer, IBD Horizons, AbbVie, Takeda, and Janssen.

Real-world practice data show that less than 10% of patients with inflammatory bowel disease (IBD) receive early treatment with monoclonal antibody vedolizumab, despite better outcomes with earlier initiation. That said, earlier initiation of vedolizumab appears to be more common in younger patients and women, according to the study findings.

Previous research supports the early use of biologics in the management of IBD, given findings that show earlier treatment is associated with increased likelihood of response and remission compared with delayed management. In actual clinical practice, biologic agents are often delayed, potentially contributing to suboptimal outcomes and increased risks of IBD-associated adverse effects.

In a real-world study presented during the 2021 Advances in Inflammatory Bowel Diseases (AIBD) meeting by Maja Kuharic, a PhD candidate at the University of Illinois at Chicago, researchers assessed administrative datasets to gauge the timing of vedolizumab utilization in adult patients with Crohn’s disease (CD) or ulcerative colitis (UC).

Data from the 2017 to 2019 MarketScan commercial and Medicare claims databases were examined in the study. Patients with continuous enrollment in the same health plan for 12 months or longer both before and after their initial IBD diagnosis were included. Additionally, the analysis included patients with 1 or more vedolizumab claim following the index IBD diagnosis.

A total of five treatment pathways were predefined for the study. First, early vedolizumab use was defined as treatment with the monoclonal antibody therapy within 30 days of the first IBD diagnostic claim. A “delayed vedolizumab 1” initiation group was defined as initial treatment with immunomodulators followed by switching to vedolizumab. Additionally, “delayed vedolizumab 2” was defined by initial utilization of corticosteroids with immunomodulators prior to vedolizumab initiation. “Delayed vedolizumab 3” was characterized by the initial use of 5-aminosalicylic acid (5-ASA) with corticosteroids before vedolizumab. Finally, “delayed vedolizumab 4” was defined by the use of 5-ASA with corticosteroids and immunomodulators before vedolizumab.

The real-world cohort study included 1,342 patients with UC (median age, 43 years; 51.0% male) and 964 patients with CD (median age, 45 years; 43.6% male) who received vedolizumab. Early vedolizumab initiation was observed in 6.6% of patients with UC and 9.6% of patients with CD. In the UC population, the proportions of patients classified in the delayed vedolizumab 1, 2, 3, and 4 groups were 7.5%, 14.8%, 37.6%, and 33.4%, respectively. Among the CD group, the proportions of patients in each delayed vedolizumab arms were 19.0%, 36.8%, 19.0%, and 15.6%, respectively.

In the UC cohort, patients who experienced early vedolizumab initiation had a median younger age than those in the delayed groups (40 vs. 44 years, respectively). Additionally, the proportion of men was lower in the early vedolizumab cohort (46.1% vs. 51.4%). Similar findings were observed in the CD group: those who initiated vedolizumab earlier had a lower median age (43 vs. 45 years) and were less frequently men (39.8%% vs. 43.9%).

Across both treatment indications, there were no clinically meaningful differences between treatment groups in terms of geographic location, payer type (that is, commercial vs. Medicare), or year of diagnosis.

According to Jean-Frederic Colombel, MD, who was asked to comment on the study, a limitation of the findings is the lack of explanation as to why early initiation of vedolizumab is higher in younger patients and women. “Rather, it just reflects clinical practice in the real world with no justification,” said Dr. Colombel, a gastroenterologist and director of the Feinstein IBD Center at Mount Sinai Hospital and professor of medicine (division of gastroenterology) at the Icahn School of Medicine at Mount Sinai in New York, who wasn’t involved in the study.

“[The findings] may look surprising since the drug, because of its safety, could be considered first-line in elderly fragile patients with higher risk of infection,” added Dr. Colombel. He noted that what is missing from the study is the longitudinal assessment of early treatment in terms of disease modification. In particular, he asked, what needs to be further explored is the “long-term impact of early vedolizumab initiation on the risk of surgery and complications.”

During another session at the AIBD 2021 meeting on the positioning of therapies in IBD, Anita Afzali, MD, of the Ohio State University Wexner Medical Center in Hilliard, Ohio, noted that for newly diagnosed patients, early initiation of vedolizumab may be most appropriate for patients with unfavorable pharmacokinetics. For instance, Dr. Afzali said, vedolizumab or ustekinumab could be the biologics of choice for an older woman with ileocolonic CD and the HLA-DQA1*04 genotype in whom clinicians would want to avoid an immunomodulator.

“When you look at different factors, whether you’re discussing the drug itself or the patient, there’s different considerations” for selecting a therapy in IBD, explained Dr. Afzali. These considerations, she stated, include those related to drug efficacy and safety as well as disease and individual characteristics such as age, comorbidities, preferences, and costs.

Ms. Kuharic is a PhD candidate and is also a Health Economics and Outcomes Research Fellow at Takeda. Dr. Colombel has consulted for Takeda, which markets vedolizumab for CD and UC. Dr. Afzali has reported relationships with several pharmaceutical companies, including BMS, Eli Lilly, Gilead, Pfizer, IBD Horizons, AbbVie, Takeda, and Janssen.

An artificial intelligence (AI) system called “ENDOANGEL” was effective for real-time monitoring of endoscopic “blind spots” and improved detection of early gastric cancer (EGC) during esophagogastroduodenoscopy (EGD), according to research published recently.

Science Photo Library/SCIEPRO/Brand X Pictures

While EGD is widely used to examine lesions found in the upper gastrointestinal tract, there is considerable variability among endoscopists regarding performance, resulting in a substantial miss rate for EGC. But in a study published in the journal Endoscopy, researchers suggest a more objective assessment of lesions with AI technology could improve detection rates in real time, thus improving the chances of establishing an early diagnosis and initiating prompt treatment of gastric cancer.

The researchers updated a developed AI system called WISENSE, which previously demonstrated an ability to monitor gastric areas overlooked during EGD (termed “blind spots”). The investigators integrated a trained real-time EGC detection model into the WISENSE system and changed the name of the updated system to ENDOANGEL.

Researchers from the Renmin Hospital of Wuhan (China) University used deep convolutional neural networks and deep reinforcement learning to develop the ENDOANGEL. A total of 1,050 patients from five hospitals in China who were undergoing EGD were randomized to either an ENDOANGEL-assisted protocol (n = 498) or a control group (n = 504) that did not use the ENDOANGEL system. Examination consisted of white-light imaging observation, magnifying image-enhanced endoscopy observation, and biopsy of suspicious lesions.

The investigators compared the groups in terms of the number of blind spots after the intervention. They assessed the performance of the AI-based ENDOANGEL system in its ability to predict EGC in a real-world clinical setting.

Patients assigned to ENDOANGEL had a significantly fewer mean number of blind spots compared with patients assigned to control (5.38 vs. 9.82, respectively; P < .001). Despite this advantage, patients in the ENDOANGEL group had significantly longer inspection time (5.40 minutes vs. 4.38 minutes; P < .001).

There were 819 lesions reported by endoscopists in the ENDOANGEL group, which included 196 gastric lesions with pathological results. According to the investigators, the ENDOANGEL system correctly predicted all three EGCs, including one mucosal carcinoma and two high grade neoplasias, as well as two advanced gastric cancers. The per-lesion accuracy was 84.7 %, while the sensitivity and specificity rates for detecting gastric cancer were 100% and 84.3%, respectively.

The authors noted limitations of the analysis itself and those stemming from the short follow-up, as well as possible bias introduced by unblinded statisticians. Further research is warranted, they wrote.

“In conclusion, ENDOANGEL, a system for improving endoscopy quality based on deep learning, achieved real-time monitoring of endoscopic blind spots, timing, and EGC detection during EGD,” according to the authors. “ENDOANGEL greatly improved the quality of EGD in this multicenter study, and showed potential for detecting EGC in real clinical settings.”
 

Spotting the blind spots

An AI-based system such as ENDOANGEL could overcome some of the natural weaknesses to standard diagnostic testing, thereby improving rates of EGC testing, David Hoffman, MD, a gastroenterology oncologist and medical director of Cedars-Sinai Cancer Beverly Hills, said in an interview. “I think that there are ethical questions that we’re going to have to grapple with respect to accessibility and data mining and what that really means,” said Dr. Hoffman, who wasn’t involved in the study. “But I think that in the optimistic view, using AI with machine learning and deep learning has tremendous potential for public health and for cancer medicine in particular.”

Dr. Hoffman added that beyond early detection of cancer, AI systems may hold additional benefits, particularly in regard to assisting decisions for personalized medicine and assisting in real-time surgical interventions. “Using AI with machine learning and deep learning has tremendous potential and I think it sort of is a natural offshoot into what we’re seeing in ... algorithmic approaches to use of big data, so it’s sort of a natural evolution in terms of medical applications,” he explained.

Anuj Patel, MD, a medical oncology specialist at the Dana-Farber Cancer Institute, Boston, who wasn’t involved in the new research, explained that any strategy that helps detect gastric cancer at earlier stages could have a visible global impact. “We have a lower incidence of gastric cancer in the United States, but the training of and clinical volume of early gastric cancers seen by different providers can vary,” Dr. Patel said in an interview. “AI systems could provide a second layer of evaluation during procedures where an endoscopist might otherwise miss the subtle features associated with some early gastric cancers.”

While the findings from the ENDOANGEL study appear promising, Dr. Patel noted that the most important long-term question is whether this reduction of endoscopic blind spots as a result of implementing the system will translate to meaningful improvements in patient outcomes. “More broadly, I think that we will need to see how well these techniques can be applied across different populations,” he added. “Because AI models such as these need to be trained, it will be important to see if they need to be retrained when used in countries where gastric cancer might present differently or with distinctive endoscopic equipment and techniques.”

The study authors, as well as Dr. Patel and Dr. Hoffman, had no conflicts of interest to disclose.

An artificial intelligence (AI) system called “ENDOANGEL” was effective for real-time monitoring of endoscopic “blind spots” and improved detection of early gastric cancer (EGC) during esophagogastroduodenoscopy (EGD), according to research published recently.

Science Photo Library/SCIEPRO/Brand X Pictures

While EGD is widely used to examine lesions found in the upper gastrointestinal tract, there is considerable variability among endoscopists regarding performance, resulting in a substantial miss rate for EGC. But in a study published in the journal Endoscopy, researchers suggest a more objective assessment of lesions with AI technology could improve detection rates in real time, thus improving the chances of establishing an early diagnosis and initiating prompt treatment of gastric cancer.

The researchers updated a developed AI system called WISENSE, which previously demonstrated an ability to monitor gastric areas overlooked during EGD (termed “blind spots”). The investigators integrated a trained real-time EGC detection model into the WISENSE system and changed the name of the updated system to ENDOANGEL.

Researchers from the Renmin Hospital of Wuhan (China) University used deep convolutional neural networks and deep reinforcement learning to develop the ENDOANGEL. A total of 1,050 patients from five hospitals in China who were undergoing EGD were randomized to either an ENDOANGEL-assisted protocol (n = 498) or a control group (n = 504) that did not use the ENDOANGEL system. Examination consisted of white-light imaging observation, magnifying image-enhanced endoscopy observation, and biopsy of suspicious lesions.

The investigators compared the groups in terms of the number of blind spots after the intervention. They assessed the performance of the AI-based ENDOANGEL system in its ability to predict EGC in a real-world clinical setting.

Patients assigned to ENDOANGEL had a significantly fewer mean number of blind spots compared with patients assigned to control (5.38 vs. 9.82, respectively; P < .001). Despite this advantage, patients in the ENDOANGEL group had significantly longer inspection time (5.40 minutes vs. 4.38 minutes; P < .001).

There were 819 lesions reported by endoscopists in the ENDOANGEL group, which included 196 gastric lesions with pathological results. According to the investigators, the ENDOANGEL system correctly predicted all three EGCs, including one mucosal carcinoma and two high grade neoplasias, as well as two advanced gastric cancers. The per-lesion accuracy was 84.7 %, while the sensitivity and specificity rates for detecting gastric cancer were 100% and 84.3%, respectively.

The authors noted limitations of the analysis itself and those stemming from the short follow-up, as well as possible bias introduced by unblinded statisticians. Further research is warranted, they wrote.

“In conclusion, ENDOANGEL, a system for improving endoscopy quality based on deep learning, achieved real-time monitoring of endoscopic blind spots, timing, and EGC detection during EGD,” according to the authors. “ENDOANGEL greatly improved the quality of EGD in this multicenter study, and showed potential for detecting EGC in real clinical settings.”
 

Spotting the blind spots

An AI-based system such as ENDOANGEL could overcome some of the natural weaknesses to standard diagnostic testing, thereby improving rates of EGC testing, David Hoffman, MD, a gastroenterology oncologist and medical director of Cedars-Sinai Cancer Beverly Hills, said in an interview. “I think that there are ethical questions that we’re going to have to grapple with respect to accessibility and data mining and what that really means,” said Dr. Hoffman, who wasn’t involved in the study. “But I think that in the optimistic view, using AI with machine learning and deep learning has tremendous potential for public health and for cancer medicine in particular.”

Dr. Hoffman added that beyond early detection of cancer, AI systems may hold additional benefits, particularly in regard to assisting decisions for personalized medicine and assisting in real-time surgical interventions. “Using AI with machine learning and deep learning has tremendous potential and I think it sort of is a natural offshoot into what we’re seeing in ... algorithmic approaches to use of big data, so it’s sort of a natural evolution in terms of medical applications,” he explained.

Anuj Patel, MD, a medical oncology specialist at the Dana-Farber Cancer Institute, Boston, who wasn’t involved in the new research, explained that any strategy that helps detect gastric cancer at earlier stages could have a visible global impact. “We have a lower incidence of gastric cancer in the United States, but the training of and clinical volume of early gastric cancers seen by different providers can vary,” Dr. Patel said in an interview. “AI systems could provide a second layer of evaluation during procedures where an endoscopist might otherwise miss the subtle features associated with some early gastric cancers.”

While the findings from the ENDOANGEL study appear promising, Dr. Patel noted that the most important long-term question is whether this reduction of endoscopic blind spots as a result of implementing the system will translate to meaningful improvements in patient outcomes. “More broadly, I think that we will need to see how well these techniques can be applied across different populations,” he added. “Because AI models such as these need to be trained, it will be important to see if they need to be retrained when used in countries where gastric cancer might present differently or with distinctive endoscopic equipment and techniques.”

The study authors, as well as Dr. Patel and Dr. Hoffman, had no conflicts of interest to disclose.

An artificial intelligence (AI) system called “ENDOANGEL” was effective for real-time monitoring of endoscopic “blind spots” and improved detection of early gastric cancer (EGC) during esophagogastroduodenoscopy (EGD), according to research published recently.

Science Photo Library/SCIEPRO/Brand X Pictures

While EGD is widely used to examine lesions found in the upper gastrointestinal tract, there is considerable variability among endoscopists regarding performance, resulting in a substantial miss rate for EGC. But in a study published in the journal Endoscopy, researchers suggest a more objective assessment of lesions with AI technology could improve detection rates in real time, thus improving the chances of establishing an early diagnosis and initiating prompt treatment of gastric cancer.

The researchers updated a developed AI system called WISENSE, which previously demonstrated an ability to monitor gastric areas overlooked during EGD (termed “blind spots”). The investigators integrated a trained real-time EGC detection model into the WISENSE system and changed the name of the updated system to ENDOANGEL.

Researchers from the Renmin Hospital of Wuhan (China) University used deep convolutional neural networks and deep reinforcement learning to develop the ENDOANGEL. A total of 1,050 patients from five hospitals in China who were undergoing EGD were randomized to either an ENDOANGEL-assisted protocol (n = 498) or a control group (n = 504) that did not use the ENDOANGEL system. Examination consisted of white-light imaging observation, magnifying image-enhanced endoscopy observation, and biopsy of suspicious lesions.

The investigators compared the groups in terms of the number of blind spots after the intervention. They assessed the performance of the AI-based ENDOANGEL system in its ability to predict EGC in a real-world clinical setting.

Patients assigned to ENDOANGEL had a significantly fewer mean number of blind spots compared with patients assigned to control (5.38 vs. 9.82, respectively; P < .001). Despite this advantage, patients in the ENDOANGEL group had significantly longer inspection time (5.40 minutes vs. 4.38 minutes; P < .001).

There were 819 lesions reported by endoscopists in the ENDOANGEL group, which included 196 gastric lesions with pathological results. According to the investigators, the ENDOANGEL system correctly predicted all three EGCs, including one mucosal carcinoma and two high grade neoplasias, as well as two advanced gastric cancers. The per-lesion accuracy was 84.7 %, while the sensitivity and specificity rates for detecting gastric cancer were 100% and 84.3%, respectively.

The authors noted limitations of the analysis itself and those stemming from the short follow-up, as well as possible bias introduced by unblinded statisticians. Further research is warranted, they wrote.

“In conclusion, ENDOANGEL, a system for improving endoscopy quality based on deep learning, achieved real-time monitoring of endoscopic blind spots, timing, and EGC detection during EGD,” according to the authors. “ENDOANGEL greatly improved the quality of EGD in this multicenter study, and showed potential for detecting EGC in real clinical settings.”
 

Spotting the blind spots

An AI-based system such as ENDOANGEL could overcome some of the natural weaknesses to standard diagnostic testing, thereby improving rates of EGC testing, David Hoffman, MD, a gastroenterology oncologist and medical director of Cedars-Sinai Cancer Beverly Hills, said in an interview. “I think that there are ethical questions that we’re going to have to grapple with respect to accessibility and data mining and what that really means,” said Dr. Hoffman, who wasn’t involved in the study. “But I think that in the optimistic view, using AI with machine learning and deep learning has tremendous potential for public health and for cancer medicine in particular.”

Dr. Hoffman added that beyond early detection of cancer, AI systems may hold additional benefits, particularly in regard to assisting decisions for personalized medicine and assisting in real-time surgical interventions. “Using AI with machine learning and deep learning has tremendous potential and I think it sort of is a natural offshoot into what we’re seeing in ... algorithmic approaches to use of big data, so it’s sort of a natural evolution in terms of medical applications,” he explained.

Anuj Patel, MD, a medical oncology specialist at the Dana-Farber Cancer Institute, Boston, who wasn’t involved in the new research, explained that any strategy that helps detect gastric cancer at earlier stages could have a visible global impact. “We have a lower incidence of gastric cancer in the United States, but the training of and clinical volume of early gastric cancers seen by different providers can vary,” Dr. Patel said in an interview. “AI systems could provide a second layer of evaluation during procedures where an endoscopist might otherwise miss the subtle features associated with some early gastric cancers.”

While the findings from the ENDOANGEL study appear promising, Dr. Patel noted that the most important long-term question is whether this reduction of endoscopic blind spots as a result of implementing the system will translate to meaningful improvements in patient outcomes. “More broadly, I think that we will need to see how well these techniques can be applied across different populations,” he added. “Because AI models such as these need to be trained, it will be important to see if they need to be retrained when used in countries where gastric cancer might present differently or with distinctive endoscopic equipment and techniques.”

The study authors, as well as Dr. Patel and Dr. Hoffman, had no conflicts of interest to disclose.

TC-325, a bentonite-derived hemostatic powder, was not inferior to standard therapy for the endoscopic management of acute nonvariceal upper GI bleeding, according to a new study.

The findings from the study, lead investigator and study author James Y.W. Lau, MD, of the Prince of Wales Hospital in Hong Kong, said in an interview, suggest TC-325 could “be considered one of the primary endoscopic treatments to actively stop nonvariceal bleeding,” particularly in cases when other therapies prove unsuccessful. The study findings were published in Annals of Internal Medicine.

The study team noted that, after they first reported the use of TC-325 in active bleeding from gastroduodenal ulcers in 2011, there have been other studies of its use with acute nonvariceal upper GI bleeding, but to date there has been only two randomized controlled trials of it as a sole endoscopic treatment option for acute nonvariceal upper GI bleeding. To close this research gap, Dr. Lau and researchers enrolled 224 adult patients with acute bleeding from a nonvariceal source on upper GI endoscopy and randomly assigned these patients to receive either TC-325 (n = 111) or standard hemostatic treatment (n = 113). Standard endoscopic bleeding management consisted of contact thermocoagulation using a heater probe or bipolar probe, or hemoclipping with or without previously injected diluted epinephrine.

Success of assigned treatment was defined by the cessation of active bleeding as well as flattening of the protuberance or vessel with a heater or bipolar probe. For the primary outcome of the study, the investigators assessed the rate of bleeding control within 30 days following randomization. Additionally, the researchers compared the treatment groups to identify differences in the failure to control bleeding during the initial endoscopy and recurrent bleeding following hemostasis.

Treatment groups were even in regard to the proportions of patients with bleeding gastroduodenal ulcers (61.3% vs. 60.2%). A smaller proportion of patients in the TC-325 arm had a history of alcohol use (3.0% vs. 9.8%) and current use of NSAIDs (8.1% vs. 20.4%). The group assigned to TC-325 had more bleeding tumors (20.7% vs. 8.8%) and fewer Dieulafoy lesions (5.4% vs. 14.2%), compared with the standard treatment arm. Additionally, patients in the TC-325 group had a higher median Glasgow-Blatchford Score at hospital admission than the standard endoscopy management group (12 vs. 11, respectively; P < .05).

Although a greater proportion of patients assigned TC-325 had bleeding controlled within 30 days of randomization (90.1% vs. 81.4%; risk difference, 8.7 percentage points; 1-sided 95% CI, 0.95 percentage points), the researchers noted that the lower limit of the confidence interval for treatment difference “did not extend beyond the prespecified noninferiority margin of 10 percentage points, indicating that TC-325 is not inferior to standard treatment in the control of bleeding.”

Fewer failures of hemostasis were observed with TC-325 during index endoscopy (2.7% vs. 9.7%; odds ratio, 0.26; 95% CI, 0.07-0.95). After initial endoscopic control, recurrent bleeding was observed in 9 patients in the TC-325 arm and 10 patients in the standard treatment group.

The authors suggested that the low recurrent bleeding rate in the TC-325 arm may reflect enhanced responsiveness in the predominantly Asian study population, a group with lower parietal cell masses and higher rates of Helicobacter pylori infections. In an accompanying editorial published online in Annals of Internal Medicine, Alan N. Barkun, MD, McGill University and McGill University Health Centre in Montreal, and Ali Alali, MB BCh BAO, in the department of medicine at Kuwait University, Kuwait City, noted that “possible additional reasons for the enhanced effectiveness of TC-325 observed in the current trial may be its varied performance in the patients with nonulcer bleeding.”

No difference was found between the treatment strategies in terms of the need for additional interventions within 30 days. The need for further endoscopic treatment was reported in 7.2% of patients in the TC-325 groups versus 8.8% of patients assigned to standard treatment. In addition, further angiography was required in 1.8% and 3.5% of patients, while further surgery was required in 0.9% of patients treated with TC-325 versus none in the standard treatment group. Each group reported 14 deaths.

Dr. Lau noted that the study enrolled Asian patients who were more responsive to proton pump inhibitor therapy, which may limit the generalizability of the findings. “We also included patients with mixed etiologies,” he added. “Studies that focus on specific lesions would further inform our practice, and larger observational studies are required to understand failures with TC-325.”

Based on the study findings, corresponding editorial author Dr. Barkun wrote that “TC-325 can be used alone in nonvariceal upper gastrointestinal bleeding or as rescue therapy but should be reserved for patients with actively bleeding lesions” and suggests the treatment option “is likely one of the most effective modalities in achieving immediate hemostasis.”

The researchers reported no conflicts of interest with the pharmaceutical industry. The editorialists also reported no disclosures of interest.

TC-325, a bentonite-derived hemostatic powder, was not inferior to standard therapy for the endoscopic management of acute nonvariceal upper GI bleeding, according to a new study.

The findings from the study, lead investigator and study author James Y.W. Lau, MD, of the Prince of Wales Hospital in Hong Kong, said in an interview, suggest TC-325 could “be considered one of the primary endoscopic treatments to actively stop nonvariceal bleeding,” particularly in cases when other therapies prove unsuccessful. The study findings were published in Annals of Internal Medicine.

The study team noted that, after they first reported the use of TC-325 in active bleeding from gastroduodenal ulcers in 2011, there have been other studies of its use with acute nonvariceal upper GI bleeding, but to date there has been only two randomized controlled trials of it as a sole endoscopic treatment option for acute nonvariceal upper GI bleeding. To close this research gap, Dr. Lau and researchers enrolled 224 adult patients with acute bleeding from a nonvariceal source on upper GI endoscopy and randomly assigned these patients to receive either TC-325 (n = 111) or standard hemostatic treatment (n = 113). Standard endoscopic bleeding management consisted of contact thermocoagulation using a heater probe or bipolar probe, or hemoclipping with or without previously injected diluted epinephrine.

Success of assigned treatment was defined by the cessation of active bleeding as well as flattening of the protuberance or vessel with a heater or bipolar probe. For the primary outcome of the study, the investigators assessed the rate of bleeding control within 30 days following randomization. Additionally, the researchers compared the treatment groups to identify differences in the failure to control bleeding during the initial endoscopy and recurrent bleeding following hemostasis.

Treatment groups were even in regard to the proportions of patients with bleeding gastroduodenal ulcers (61.3% vs. 60.2%). A smaller proportion of patients in the TC-325 arm had a history of alcohol use (3.0% vs. 9.8%) and current use of NSAIDs (8.1% vs. 20.4%). The group assigned to TC-325 had more bleeding tumors (20.7% vs. 8.8%) and fewer Dieulafoy lesions (5.4% vs. 14.2%), compared with the standard treatment arm. Additionally, patients in the TC-325 group had a higher median Glasgow-Blatchford Score at hospital admission than the standard endoscopy management group (12 vs. 11, respectively; P < .05).

Although a greater proportion of patients assigned TC-325 had bleeding controlled within 30 days of randomization (90.1% vs. 81.4%; risk difference, 8.7 percentage points; 1-sided 95% CI, 0.95 percentage points), the researchers noted that the lower limit of the confidence interval for treatment difference “did not extend beyond the prespecified noninferiority margin of 10 percentage points, indicating that TC-325 is not inferior to standard treatment in the control of bleeding.”

Fewer failures of hemostasis were observed with TC-325 during index endoscopy (2.7% vs. 9.7%; odds ratio, 0.26; 95% CI, 0.07-0.95). After initial endoscopic control, recurrent bleeding was observed in 9 patients in the TC-325 arm and 10 patients in the standard treatment group.

The authors suggested that the low recurrent bleeding rate in the TC-325 arm may reflect enhanced responsiveness in the predominantly Asian study population, a group with lower parietal cell masses and higher rates of Helicobacter pylori infections. In an accompanying editorial published online in Annals of Internal Medicine, Alan N. Barkun, MD, McGill University and McGill University Health Centre in Montreal, and Ali Alali, MB BCh BAO, in the department of medicine at Kuwait University, Kuwait City, noted that “possible additional reasons for the enhanced effectiveness of TC-325 observed in the current trial may be its varied performance in the patients with nonulcer bleeding.”

No difference was found between the treatment strategies in terms of the need for additional interventions within 30 days. The need for further endoscopic treatment was reported in 7.2% of patients in the TC-325 groups versus 8.8% of patients assigned to standard treatment. In addition, further angiography was required in 1.8% and 3.5% of patients, while further surgery was required in 0.9% of patients treated with TC-325 versus none in the standard treatment group. Each group reported 14 deaths.

Dr. Lau noted that the study enrolled Asian patients who were more responsive to proton pump inhibitor therapy, which may limit the generalizability of the findings. “We also included patients with mixed etiologies,” he added. “Studies that focus on specific lesions would further inform our practice, and larger observational studies are required to understand failures with TC-325.”

Based on the study findings, corresponding editorial author Dr. Barkun wrote that “TC-325 can be used alone in nonvariceal upper gastrointestinal bleeding or as rescue therapy but should be reserved for patients with actively bleeding lesions” and suggests the treatment option “is likely one of the most effective modalities in achieving immediate hemostasis.”

The researchers reported no conflicts of interest with the pharmaceutical industry. The editorialists also reported no disclosures of interest.

TC-325, a bentonite-derived hemostatic powder, was not inferior to standard therapy for the endoscopic management of acute nonvariceal upper GI bleeding, according to a new study.

The findings from the study, lead investigator and study author James Y.W. Lau, MD, of the Prince of Wales Hospital in Hong Kong, said in an interview, suggest TC-325 could “be considered one of the primary endoscopic treatments to actively stop nonvariceal bleeding,” particularly in cases when other therapies prove unsuccessful. The study findings were published in Annals of Internal Medicine.

The study team noted that, after they first reported the use of TC-325 in active bleeding from gastroduodenal ulcers in 2011, there have been other studies of its use with acute nonvariceal upper GI bleeding, but to date there has been only two randomized controlled trials of it as a sole endoscopic treatment option for acute nonvariceal upper GI bleeding. To close this research gap, Dr. Lau and researchers enrolled 224 adult patients with acute bleeding from a nonvariceal source on upper GI endoscopy and randomly assigned these patients to receive either TC-325 (n = 111) or standard hemostatic treatment (n = 113). Standard endoscopic bleeding management consisted of contact thermocoagulation using a heater probe or bipolar probe, or hemoclipping with or without previously injected diluted epinephrine.

Success of assigned treatment was defined by the cessation of active bleeding as well as flattening of the protuberance or vessel with a heater or bipolar probe. For the primary outcome of the study, the investigators assessed the rate of bleeding control within 30 days following randomization. Additionally, the researchers compared the treatment groups to identify differences in the failure to control bleeding during the initial endoscopy and recurrent bleeding following hemostasis.

Treatment groups were even in regard to the proportions of patients with bleeding gastroduodenal ulcers (61.3% vs. 60.2%). A smaller proportion of patients in the TC-325 arm had a history of alcohol use (3.0% vs. 9.8%) and current use of NSAIDs (8.1% vs. 20.4%). The group assigned to TC-325 had more bleeding tumors (20.7% vs. 8.8%) and fewer Dieulafoy lesions (5.4% vs. 14.2%), compared with the standard treatment arm. Additionally, patients in the TC-325 group had a higher median Glasgow-Blatchford Score at hospital admission than the standard endoscopy management group (12 vs. 11, respectively; P < .05).

Although a greater proportion of patients assigned TC-325 had bleeding controlled within 30 days of randomization (90.1% vs. 81.4%; risk difference, 8.7 percentage points; 1-sided 95% CI, 0.95 percentage points), the researchers noted that the lower limit of the confidence interval for treatment difference “did not extend beyond the prespecified noninferiority margin of 10 percentage points, indicating that TC-325 is not inferior to standard treatment in the control of bleeding.”

Fewer failures of hemostasis were observed with TC-325 during index endoscopy (2.7% vs. 9.7%; odds ratio, 0.26; 95% CI, 0.07-0.95). After initial endoscopic control, recurrent bleeding was observed in 9 patients in the TC-325 arm and 10 patients in the standard treatment group.

The authors suggested that the low recurrent bleeding rate in the TC-325 arm may reflect enhanced responsiveness in the predominantly Asian study population, a group with lower parietal cell masses and higher rates of Helicobacter pylori infections. In an accompanying editorial published online in Annals of Internal Medicine, Alan N. Barkun, MD, McGill University and McGill University Health Centre in Montreal, and Ali Alali, MB BCh BAO, in the department of medicine at Kuwait University, Kuwait City, noted that “possible additional reasons for the enhanced effectiveness of TC-325 observed in the current trial may be its varied performance in the patients with nonulcer bleeding.”

No difference was found between the treatment strategies in terms of the need for additional interventions within 30 days. The need for further endoscopic treatment was reported in 7.2% of patients in the TC-325 groups versus 8.8% of patients assigned to standard treatment. In addition, further angiography was required in 1.8% and 3.5% of patients, while further surgery was required in 0.9% of patients treated with TC-325 versus none in the standard treatment group. Each group reported 14 deaths.

Dr. Lau noted that the study enrolled Asian patients who were more responsive to proton pump inhibitor therapy, which may limit the generalizability of the findings. “We also included patients with mixed etiologies,” he added. “Studies that focus on specific lesions would further inform our practice, and larger observational studies are required to understand failures with TC-325.”

Based on the study findings, corresponding editorial author Dr. Barkun wrote that “TC-325 can be used alone in nonvariceal upper gastrointestinal bleeding or as rescue therapy but should be reserved for patients with actively bleeding lesions” and suggests the treatment option “is likely one of the most effective modalities in achieving immediate hemostasis.”

The researchers reported no conflicts of interest with the pharmaceutical industry. The editorialists also reported no disclosures of interest.

Treatment with endoscopic submucosal dissection (ESD) is associated with higher rates of complete remission of dysplasia at 2 years, compared with cap-assisted endoscopic mucosal resection (cEMR) in patients with Barrett’s esophagus with dysplasia or early-stage intramucosal esophageal adenocarcinoma (EAC), according to study findings.

Despite the seeming advantage of ESD over cEMR, the study found similar rates of complete remission of intestinal metaplasia (CRIM) between the treatment groups at 2 years.

The study authors explained that ESD, a recent development in endoscopic resection, allows for en bloc resection of larger lesions in dysplastic Barrett’s and EAC and features less diagnostic uncertainty, compared with cEMR. Findings from the study highlight the importance of this newer technique but also emphasize the utility of both treatments. “In expert hands both sets of procedures appear to be safe and well tolerated,” wrote study authors Don Codipilly, MD, of the Mayo Clinic in Rochester, Minn., and colleagues in Clinical Gastroenterology and Hepatology.

Given the lack of comparative data on the long-term outcomes of cEMR versus ESD in patients with neoplasia associated with Barrett’s esophagus, Dr. Codipilly and colleagues examined histologic outcomes in a prospectively maintained database of 537 patients who underwent endoscopic eradication therapy for Barrett’s esophagus or EAC at the Mayo Clinic between 2006 and 2020. Only patients who had undergone either cEMR (n = 456) or ESD (n = 81) followed by endoscopic ablation were included in the analysis.

The primary endpoint of the study was the rate and time to complete remission of dysplasia (CRD), which was defined by the absence of dysplasia on biopsy from the gastroesophageal junction and tubular esophagus during at least one surveillance endoscopy. Researchers also examined the rates of complications, such as clinically significant intraprocedural or postprocedural bleeding that required hospitalization, perforation, receipt of red blood cells within 30 days of the initial procedure, and stricture formation that required dilation within 120 days of the index procedure.

Patients in the ESD group had a longer mean length of resected specimens (23.9 vs. 10.9 mm; P < .01) as well as higher rates of en bloc (97.5% vs. 41.9%; P < .01) and R0 resection (58% vs. 20.2%; P < .01). Patients were generally balanced on other basic baseline demographics, including age, sex distribution, and smoking status.

Over a median 11.2-year follow-up period, a total of 420 patients in the cEMR group achieved CRD. In the ESD group, 48 patients achieved CRD over a median 1.4-year follow-up period. The 2-year cumulative probability of CRD was lower in patients who received cEMR versus those who received ESD (75.8% vs. 85.6%, respectively). In a univariate analysis, the odds of achieving CRD were lower in cEMR versus ESD (hazard ratio, 0.41; 95% CI, 0.31-0.54; P < .01).

According to multivariate analysis, two independent predictors of CRD included ESD (hazard ratio, 2.38; P <.01) and shorter Barrett’s segment length (HR, 1.11; P < .01).

The investigators also assessed whether advancements made in cEMR technique have contributed to the findings in an analysis of patients who underwent cEMR (n = 48) with ESD (n = 80) from 2015 to 2019. In this analysis, the researchers found that the odds of CRD were lower than that of ESD (HR, 0.67; 95% CI, 0.45-0.99). Additionally, higher odds of achieving CRD in the cEMR group were observed in years between 2013 and 2019 (n = 129), compared with years 2006-2012 (n = 112) (HR, 2.09; 95% CI, 1.59-2.75; P < .01).

Demographic and clinical variables were incorporated into a Cox proportional hazard model to identify factors associated with decreased odds of CRD. This analysis found that decreased odds of CRD were associated with longer Barrett’s esophagus segment length (HR, 0.90; P <.01) and treatment with cEMR versus ESD (HR, 0.42; P < .01).

Over median follow-up periods of 7.8 years in the cEMR group and 1.1 years in the ESD group, approximately 78.5% and 40.7% of patients, respectively, achieved CRIM. While those in the ESD group achieved CRIM earlier, the cumulative probabilities of CRIM were similar by 2 years (59.3% vs. 50.6%; HR, 0.74; 95% CI, 0.52-1.07; P = .11). Shorter Barrett’s esophagus segment was the only independent predictor of CRIM (HR, 1.16; P < .01).

The researchers noted that the study population may have included patients with more severe disease than that in the general population, which may limit the generalizability of the findings. Additionally, the lack of a randomized design was cited as an additional study limitation.

In spite of their findings, the researchers explained that “continued monitoring for additional outcomes such as recurrence are required for further elucidation of the optimal role of these procedures in the management of” neoplasia associated with Barrett’s esophagus.”

The study was funded by the National Cancer Institute and the Freeman Foundation. The researchers reported no conflicts of interest with any pharmaceutical companies.

Treatment with endoscopic submucosal dissection (ESD) is associated with higher rates of complete remission of dysplasia at 2 years, compared with cap-assisted endoscopic mucosal resection (cEMR) in patients with Barrett’s esophagus with dysplasia or early-stage intramucosal esophageal adenocarcinoma (EAC), according to study findings.

Despite the seeming advantage of ESD over cEMR, the study found similar rates of complete remission of intestinal metaplasia (CRIM) between the treatment groups at 2 years.

The study authors explained that ESD, a recent development in endoscopic resection, allows for en bloc resection of larger lesions in dysplastic Barrett’s and EAC and features less diagnostic uncertainty, compared with cEMR. Findings from the study highlight the importance of this newer technique but also emphasize the utility of both treatments. “In expert hands both sets of procedures appear to be safe and well tolerated,” wrote study authors Don Codipilly, MD, of the Mayo Clinic in Rochester, Minn., and colleagues in Clinical Gastroenterology and Hepatology.

Given the lack of comparative data on the long-term outcomes of cEMR versus ESD in patients with neoplasia associated with Barrett’s esophagus, Dr. Codipilly and colleagues examined histologic outcomes in a prospectively maintained database of 537 patients who underwent endoscopic eradication therapy for Barrett’s esophagus or EAC at the Mayo Clinic between 2006 and 2020. Only patients who had undergone either cEMR (n = 456) or ESD (n = 81) followed by endoscopic ablation were included in the analysis.

The primary endpoint of the study was the rate and time to complete remission of dysplasia (CRD), which was defined by the absence of dysplasia on biopsy from the gastroesophageal junction and tubular esophagus during at least one surveillance endoscopy. Researchers also examined the rates of complications, such as clinically significant intraprocedural or postprocedural bleeding that required hospitalization, perforation, receipt of red blood cells within 30 days of the initial procedure, and stricture formation that required dilation within 120 days of the index procedure.

Patients in the ESD group had a longer mean length of resected specimens (23.9 vs. 10.9 mm; P < .01) as well as higher rates of en bloc (97.5% vs. 41.9%; P < .01) and R0 resection (58% vs. 20.2%; P < .01). Patients were generally balanced on other basic baseline demographics, including age, sex distribution, and smoking status.

Over a median 11.2-year follow-up period, a total of 420 patients in the cEMR group achieved CRD. In the ESD group, 48 patients achieved CRD over a median 1.4-year follow-up period. The 2-year cumulative probability of CRD was lower in patients who received cEMR versus those who received ESD (75.8% vs. 85.6%, respectively). In a univariate analysis, the odds of achieving CRD were lower in cEMR versus ESD (hazard ratio, 0.41; 95% CI, 0.31-0.54; P < .01).

According to multivariate analysis, two independent predictors of CRD included ESD (hazard ratio, 2.38; P <.01) and shorter Barrett’s segment length (HR, 1.11; P < .01).

The investigators also assessed whether advancements made in cEMR technique have contributed to the findings in an analysis of patients who underwent cEMR (n = 48) with ESD (n = 80) from 2015 to 2019. In this analysis, the researchers found that the odds of CRD were lower than that of ESD (HR, 0.67; 95% CI, 0.45-0.99). Additionally, higher odds of achieving CRD in the cEMR group were observed in years between 2013 and 2019 (n = 129), compared with years 2006-2012 (n = 112) (HR, 2.09; 95% CI, 1.59-2.75; P < .01).

Demographic and clinical variables were incorporated into a Cox proportional hazard model to identify factors associated with decreased odds of CRD. This analysis found that decreased odds of CRD were associated with longer Barrett’s esophagus segment length (HR, 0.90; P <.01) and treatment with cEMR versus ESD (HR, 0.42; P < .01).

Over median follow-up periods of 7.8 years in the cEMR group and 1.1 years in the ESD group, approximately 78.5% and 40.7% of patients, respectively, achieved CRIM. While those in the ESD group achieved CRIM earlier, the cumulative probabilities of CRIM were similar by 2 years (59.3% vs. 50.6%; HR, 0.74; 95% CI, 0.52-1.07; P = .11). Shorter Barrett’s esophagus segment was the only independent predictor of CRIM (HR, 1.16; P < .01).

The researchers noted that the study population may have included patients with more severe disease than that in the general population, which may limit the generalizability of the findings. Additionally, the lack of a randomized design was cited as an additional study limitation.

In spite of their findings, the researchers explained that “continued monitoring for additional outcomes such as recurrence are required for further elucidation of the optimal role of these procedures in the management of” neoplasia associated with Barrett’s esophagus.”

The study was funded by the National Cancer Institute and the Freeman Foundation. The researchers reported no conflicts of interest with any pharmaceutical companies.

Treatment with endoscopic submucosal dissection (ESD) is associated with higher rates of complete remission of dysplasia at 2 years, compared with cap-assisted endoscopic mucosal resection (cEMR) in patients with Barrett’s esophagus with dysplasia or early-stage intramucosal esophageal adenocarcinoma (EAC), according to study findings.

Despite the seeming advantage of ESD over cEMR, the study found similar rates of complete remission of intestinal metaplasia (CRIM) between the treatment groups at 2 years.

The study authors explained that ESD, a recent development in endoscopic resection, allows for en bloc resection of larger lesions in dysplastic Barrett’s and EAC and features less diagnostic uncertainty, compared with cEMR. Findings from the study highlight the importance of this newer technique but also emphasize the utility of both treatments. “In expert hands both sets of procedures appear to be safe and well tolerated,” wrote study authors Don Codipilly, MD, of the Mayo Clinic in Rochester, Minn., and colleagues in Clinical Gastroenterology and Hepatology.

Given the lack of comparative data on the long-term outcomes of cEMR versus ESD in patients with neoplasia associated with Barrett’s esophagus, Dr. Codipilly and colleagues examined histologic outcomes in a prospectively maintained database of 537 patients who underwent endoscopic eradication therapy for Barrett’s esophagus or EAC at the Mayo Clinic between 2006 and 2020. Only patients who had undergone either cEMR (n = 456) or ESD (n = 81) followed by endoscopic ablation were included in the analysis.

The primary endpoint of the study was the rate and time to complete remission of dysplasia (CRD), which was defined by the absence of dysplasia on biopsy from the gastroesophageal junction and tubular esophagus during at least one surveillance endoscopy. Researchers also examined the rates of complications, such as clinically significant intraprocedural or postprocedural bleeding that required hospitalization, perforation, receipt of red blood cells within 30 days of the initial procedure, and stricture formation that required dilation within 120 days of the index procedure.

Patients in the ESD group had a longer mean length of resected specimens (23.9 vs. 10.9 mm; P < .01) as well as higher rates of en bloc (97.5% vs. 41.9%; P < .01) and R0 resection (58% vs. 20.2%; P < .01). Patients were generally balanced on other basic baseline demographics, including age, sex distribution, and smoking status.

Over a median 11.2-year follow-up period, a total of 420 patients in the cEMR group achieved CRD. In the ESD group, 48 patients achieved CRD over a median 1.4-year follow-up period. The 2-year cumulative probability of CRD was lower in patients who received cEMR versus those who received ESD (75.8% vs. 85.6%, respectively). In a univariate analysis, the odds of achieving CRD were lower in cEMR versus ESD (hazard ratio, 0.41; 95% CI, 0.31-0.54; P < .01).

According to multivariate analysis, two independent predictors of CRD included ESD (hazard ratio, 2.38; P <.01) and shorter Barrett’s segment length (HR, 1.11; P < .01).

The investigators also assessed whether advancements made in cEMR technique have contributed to the findings in an analysis of patients who underwent cEMR (n = 48) with ESD (n = 80) from 2015 to 2019. In this analysis, the researchers found that the odds of CRD were lower than that of ESD (HR, 0.67; 95% CI, 0.45-0.99). Additionally, higher odds of achieving CRD in the cEMR group were observed in years between 2013 and 2019 (n = 129), compared with years 2006-2012 (n = 112) (HR, 2.09; 95% CI, 1.59-2.75; P < .01).

Demographic and clinical variables were incorporated into a Cox proportional hazard model to identify factors associated with decreased odds of CRD. This analysis found that decreased odds of CRD were associated with longer Barrett’s esophagus segment length (HR, 0.90; P <.01) and treatment with cEMR versus ESD (HR, 0.42; P < .01).

Over median follow-up periods of 7.8 years in the cEMR group and 1.1 years in the ESD group, approximately 78.5% and 40.7% of patients, respectively, achieved CRIM. While those in the ESD group achieved CRIM earlier, the cumulative probabilities of CRIM were similar by 2 years (59.3% vs. 50.6%; HR, 0.74; 95% CI, 0.52-1.07; P = .11). Shorter Barrett’s esophagus segment was the only independent predictor of CRIM (HR, 1.16; P < .01).

The researchers noted that the study population may have included patients with more severe disease than that in the general population, which may limit the generalizability of the findings. Additionally, the lack of a randomized design was cited as an additional study limitation.

In spite of their findings, the researchers explained that “continued monitoring for additional outcomes such as recurrence are required for further elucidation of the optimal role of these procedures in the management of” neoplasia associated with Barrett’s esophagus.”

The study was funded by the National Cancer Institute and the Freeman Foundation. The researchers reported no conflicts of interest with any pharmaceutical companies.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a two-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.