IBD & Intestinal Disorders

Segmental rather than total colectomy may be a safe and effective choice for some patients with colonic Crohn’s disease (cCD), showing significantly lower rates of repeat surgery and reduced need for stoma, according to long-term data.

Gianluca Pellino, MD, with the department of advanced medical and surgical sciences, Università degli Studi della Campania “Luigi Vanvitelli” in Naples, Italy, led the study, which was published in the Journal of Crohn’s and Colitis.

CD of the colon has gotten less attention than the more prevalent small bowel disease, according to the authors, but it can be debilitating and permanently reduce quality of life. Isolated cCD incidence ranges between 14% and 32% of all CD cases from the start of disease. Historically, extensive resection has been linked with longer disease-free intervals, and reduced repeat surgeries compared with segmental resections. However, most of the data have included low-quality evidence and reports typically have not adequately considered the role of biologics or advances in perioperative management of patients with cCD, the authors wrote.

The Segmental Colectomy for Crohn’s disease (SCOTCH) international study included a retrospective analysis of data from six European Inflammatory Bowel Disease referral centers on patients operated on between 2000 and 2019 who had either segmental or total colectomy for cCD.

Among 687 patients (301 male; 386 female), segmental colectomy was performed in 285 (41.5%) of cases and total colectomy in 402 (58.5%). The 15-year surgical recurrence rate was 44% among patients who had TC and 27% for patients with segmental colectomy (P = .006).

The SCOTCH study found that segmental colectomy may be performed safely and effectively and reduce the need for stoma in cCD patients without increasing risk of repeat surgeries compared with total colectomy, which was the primary measure investigators studied.

The findings of this study also suggest that biologics, when used early and correctly, may allow more conservative options for cCD, with a fivefold reduction in surgical recurrence risk in patients who have one to three large bowel locations.

Morbidity and mortality were similar in the SC and TC groups.

Among the limitations of the study are that the total colectomy patients in the study had indications for total colectomy that were also higher risk factors for recurrence – for instance, perianal disease.

The authors wrote, “The differences between patients who underwent SC vs TC might have accounted for the choice of one treatment over the other. It is however difficult to obtain a homogenous population of cCD patients.” They also cite the difficulties in gathering enough patients for randomized trials.

“These findings need to be discussed with the patients, and the choice of operation should be individualised,” they concluded. “Multidisciplinary management of patients with cCD is of critical importance to achieve optimal long-term results of bowel-sparing approaches.”

Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic, who was not part of the study, told this publication the findings should be considered confirmatory rather than suggestive of practice change.

“If a patient has a limited segment of Crohn’s, for example ileocecal Crohn’s – a common phenotype – then the standard of care is a segmental resection and primary anastomosis,” he said. “If the patient has more extensive CD – perianal fistula, colonic-only CD – they’re more likely to undergo a total colectomy. This study confirms that.“

The authors and Dr. Regueiro declared no relevant financial relationships.

Segmental rather than total colectomy may be a safe and effective choice for some patients with colonic Crohn’s disease (cCD), showing significantly lower rates of repeat surgery and reduced need for stoma, according to long-term data.

Gianluca Pellino, MD, with the department of advanced medical and surgical sciences, Università degli Studi della Campania “Luigi Vanvitelli” in Naples, Italy, led the study, which was published in the Journal of Crohn’s and Colitis.

CD of the colon has gotten less attention than the more prevalent small bowel disease, according to the authors, but it can be debilitating and permanently reduce quality of life. Isolated cCD incidence ranges between 14% and 32% of all CD cases from the start of disease. Historically, extensive resection has been linked with longer disease-free intervals, and reduced repeat surgeries compared with segmental resections. However, most of the data have included low-quality evidence and reports typically have not adequately considered the role of biologics or advances in perioperative management of patients with cCD, the authors wrote.

The Segmental Colectomy for Crohn’s disease (SCOTCH) international study included a retrospective analysis of data from six European Inflammatory Bowel Disease referral centers on patients operated on between 2000 and 2019 who had either segmental or total colectomy for cCD.

Among 687 patients (301 male; 386 female), segmental colectomy was performed in 285 (41.5%) of cases and total colectomy in 402 (58.5%). The 15-year surgical recurrence rate was 44% among patients who had TC and 27% for patients with segmental colectomy (P = .006).

The SCOTCH study found that segmental colectomy may be performed safely and effectively and reduce the need for stoma in cCD patients without increasing risk of repeat surgeries compared with total colectomy, which was the primary measure investigators studied.

The findings of this study also suggest that biologics, when used early and correctly, may allow more conservative options for cCD, with a fivefold reduction in surgical recurrence risk in patients who have one to three large bowel locations.

Morbidity and mortality were similar in the SC and TC groups.

Among the limitations of the study are that the total colectomy patients in the study had indications for total colectomy that were also higher risk factors for recurrence – for instance, perianal disease.

The authors wrote, “The differences between patients who underwent SC vs TC might have accounted for the choice of one treatment over the other. It is however difficult to obtain a homogenous population of cCD patients.” They also cite the difficulties in gathering enough patients for randomized trials.

“These findings need to be discussed with the patients, and the choice of operation should be individualised,” they concluded. “Multidisciplinary management of patients with cCD is of critical importance to achieve optimal long-term results of bowel-sparing approaches.”

Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic, who was not part of the study, told this publication the findings should be considered confirmatory rather than suggestive of practice change.

“If a patient has a limited segment of Crohn’s, for example ileocecal Crohn’s – a common phenotype – then the standard of care is a segmental resection and primary anastomosis,” he said. “If the patient has more extensive CD – perianal fistula, colonic-only CD – they’re more likely to undergo a total colectomy. This study confirms that.“

The authors and Dr. Regueiro declared no relevant financial relationships.

Segmental rather than total colectomy may be a safe and effective choice for some patients with colonic Crohn’s disease (cCD), showing significantly lower rates of repeat surgery and reduced need for stoma, according to long-term data.

Gianluca Pellino, MD, with the department of advanced medical and surgical sciences, Università degli Studi della Campania “Luigi Vanvitelli” in Naples, Italy, led the study, which was published in the Journal of Crohn’s and Colitis.

CD of the colon has gotten less attention than the more prevalent small bowel disease, according to the authors, but it can be debilitating and permanently reduce quality of life. Isolated cCD incidence ranges between 14% and 32% of all CD cases from the start of disease. Historically, extensive resection has been linked with longer disease-free intervals, and reduced repeat surgeries compared with segmental resections. However, most of the data have included low-quality evidence and reports typically have not adequately considered the role of biologics or advances in perioperative management of patients with cCD, the authors wrote.

The Segmental Colectomy for Crohn’s disease (SCOTCH) international study included a retrospective analysis of data from six European Inflammatory Bowel Disease referral centers on patients operated on between 2000 and 2019 who had either segmental or total colectomy for cCD.

Among 687 patients (301 male; 386 female), segmental colectomy was performed in 285 (41.5%) of cases and total colectomy in 402 (58.5%). The 15-year surgical recurrence rate was 44% among patients who had TC and 27% for patients with segmental colectomy (P = .006).

The SCOTCH study found that segmental colectomy may be performed safely and effectively and reduce the need for stoma in cCD patients without increasing risk of repeat surgeries compared with total colectomy, which was the primary measure investigators studied.

The findings of this study also suggest that biologics, when used early and correctly, may allow more conservative options for cCD, with a fivefold reduction in surgical recurrence risk in patients who have one to three large bowel locations.

Morbidity and mortality were similar in the SC and TC groups.

Among the limitations of the study are that the total colectomy patients in the study had indications for total colectomy that were also higher risk factors for recurrence – for instance, perianal disease.

The authors wrote, “The differences between patients who underwent SC vs TC might have accounted for the choice of one treatment over the other. It is however difficult to obtain a homogenous population of cCD patients.” They also cite the difficulties in gathering enough patients for randomized trials.

“These findings need to be discussed with the patients, and the choice of operation should be individualised,” they concluded. “Multidisciplinary management of patients with cCD is of critical importance to achieve optimal long-term results of bowel-sparing approaches.”

Miguel Regueiro, MD, chair of the department of gastroenterology, hepatology, and nutrition at the Cleveland Clinic, who was not part of the study, told this publication the findings should be considered confirmatory rather than suggestive of practice change.

“If a patient has a limited segment of Crohn’s, for example ileocecal Crohn’s – a common phenotype – then the standard of care is a segmental resection and primary anastomosis,” he said. “If the patient has more extensive CD – perianal fistula, colonic-only CD – they’re more likely to undergo a total colectomy. This study confirms that.“

The authors and Dr. Regueiro declared no relevant financial relationships.

Endoscopic balloon dilation (EBD) is an effective treatment option for strictures of the small bowel in patients with Crohn’s disease, based on a nationwide Danish cohort study.

Approximately three out of four patients who underwent an EBD were spared subsequent small bowel surgery. Similar outcomes were seen across primary and postsurgical strictures, reported lead author Mads Damsgaard Wewer, BSc, of the University of Copenhagen, and colleagues.

“Retrospective studies investigating EBD are available with variable follow-up periods; however, a nationwide study to demonstrate more precise durability of EBD in unselected patients is lacking,” the investigators wrote in European Journal of Gastroenterology & Hepatology. Their aim was to understand the use of EBD and the need for redilation and surgery. This retrospective study used a cohort of adult patients with Crohn’s disease who had strictures of the small bowel during a 19-year period.

The population comprised 9,737 patients with incident Crohn’s disease, among whom 90 (1%) underwent EBD during a median 8.2-year follow-up period. Of these 90 patients, 49 had primary strictures, while the remaining 41 had postsurgical strictures.

In the primary stricture group, 59% of patients had one EBD procedure and did not require subsequent small bowel surgery, 14% of patients required redilation but no further surgery, and 27% of patients required small bowel surgery after dilation. In this same group, the 1-, 3-, and 5-year cumulative incidence rates of EBD failure were 19%, 21%, and 25%, respectively. Of note, just 8% of patients with primary stricture who were treated with EBD ultimately required enterotomy, compared with 16% of patients with primary stricture who underwent small bowel resection without first attempting EBD.

In the postsurgical stricture group, 49% of patients underwent one EBD procedure without need for another small bowel surgery, 27% needed redilation but avoided surgery, and 24% required surgery after dilation. One-, three-, and five-year cumulative incidence rates of EBD failure in this group trended slightly higher than the primary stricture group over time, at 19%, 25%, and 29%, respectively.

The researchers noted that 25% of patients required small bowel surgery after EBD, which falls below rates of 29% to 33% reported by recent studies. They explained that this edge may be “partly explained by the careful selection of patients (with few and short strictures) receiving EBD,” as well as exclusion of patients with strictures outside the small intestine. They concluded that, “... small bowel-related EBD is an effective treatment option, and one that could be offered to more patients with Crohn’s disease in the future.”
 

‘Reassuring study’

David H. Bruining, MD, associate professor of medicine and section head of the inflammatory bowel disease interest group at Mayo Clinic, Rochester, Minn., called it a “reassuring study that confirms previous data regarding the efficacy of endoscopic balloon dilation of Crohn’s disease strictures.”

Dr. Bruining suggested in an interview that the findings, while drawn from Denmark, can be applied to a U.S. population; he also noted the “impressive” size of the study, as well the duration of follow-up, which extended up to 19 years.

EBD is “gaining more traction,” Dr. Bruining said, “as far as the belief among both referring physicians, and gastroenterologists, that it is effective, and it is safe. I think that body of literature is growing, and it’s more widely established at this point.”

Dr. Bruining noted that EBD should be reserved for patients who have short strictures no longer than 4-5 mm “without associated internal penetrating disease.”

In the future, such patients may have even more treatment options, Dr. Bruining predicted. New antifibrotic medications are “on the horizon,” which could one day be used with or without EBD to address fibrotic strictures in Crohn’s disease. Dr. Bruining is a part of the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium, a group that aims to develop this emerging approach. He and his colleagues recently published a review of research into antifibrotic therapy to date.


 

Limiting factors

“This is an important study that really adds something to the literature,” noted Joseph Carmichael, MD, chief medical officer and chief of colon and rectal surgery at the University of California, Irvine. “The cohort is a little unusual in this area in that it encompasses a whole country. Yet this is exactly what makes the data stand apart from previous studies, since the patient population was unselected. That’s how you get a true incidence of the intervention.”

Beyond the generally favorable outcomes associated with EBD, Dr. Carmichael highlighted similar rates of success across both primary and postsurgical strictures. “Some of the previous data suggest postsurgical strictures don’t do as well with endoscopic dilation, and this [study] seems to go against that,” he said. “Which really deserves a closer look.”

Reflecting on the researchers’ call for more frequent use of EBD in patients with Crohn’s disease, Dr. Carmichael speculated that several factors may be limiting current utilization in Europe and the U.S. For one, there may not be enough interventional gastroenterologists. Also, the procedure “generally requires a high-volume provider who’s got surgical backup because these [procedures] have a 2% to 4% incidence of technical failure – including perforation or bleeding. These risks may deter patients from undergoing the procedure.

“Patients with Crohn’s disease can be pretty remarkable in their ability to endure obstruction,” he added. “If someone’s feeling their symptoms aren’t altering their quality of life, they may choose not to proceed with it.”

With all candidate patients, Dr. Carmichael recommended discussing the risks of EBD compared with the risks of declining the intervention, such as complete bowel obstruction, bowel perforation, or fistula. “That’s a question that needs to be included with every conversation when we discuss procedures,” he explained.

The researchers report that, among others, they have relationships with Janssen-Cilag, AbbVie A/S, and Celgene. Dr. Bruining and Dr. Carmichael reports no relevant conflicts of interest.

This article was updated 7/29/22.

Endoscopic balloon dilation (EBD) is an effective treatment option for strictures of the small bowel in patients with Crohn’s disease, based on a nationwide Danish cohort study.

Approximately three out of four patients who underwent an EBD were spared subsequent small bowel surgery. Similar outcomes were seen across primary and postsurgical strictures, reported lead author Mads Damsgaard Wewer, BSc, of the University of Copenhagen, and colleagues.

“Retrospective studies investigating EBD are available with variable follow-up periods; however, a nationwide study to demonstrate more precise durability of EBD in unselected patients is lacking,” the investigators wrote in European Journal of Gastroenterology & Hepatology. Their aim was to understand the use of EBD and the need for redilation and surgery. This retrospective study used a cohort of adult patients with Crohn’s disease who had strictures of the small bowel during a 19-year period.

The population comprised 9,737 patients with incident Crohn’s disease, among whom 90 (1%) underwent EBD during a median 8.2-year follow-up period. Of these 90 patients, 49 had primary strictures, while the remaining 41 had postsurgical strictures.

In the primary stricture group, 59% of patients had one EBD procedure and did not require subsequent small bowel surgery, 14% of patients required redilation but no further surgery, and 27% of patients required small bowel surgery after dilation. In this same group, the 1-, 3-, and 5-year cumulative incidence rates of EBD failure were 19%, 21%, and 25%, respectively. Of note, just 8% of patients with primary stricture who were treated with EBD ultimately required enterotomy, compared with 16% of patients with primary stricture who underwent small bowel resection without first attempting EBD.

In the postsurgical stricture group, 49% of patients underwent one EBD procedure without need for another small bowel surgery, 27% needed redilation but avoided surgery, and 24% required surgery after dilation. One-, three-, and five-year cumulative incidence rates of EBD failure in this group trended slightly higher than the primary stricture group over time, at 19%, 25%, and 29%, respectively.

The researchers noted that 25% of patients required small bowel surgery after EBD, which falls below rates of 29% to 33% reported by recent studies. They explained that this edge may be “partly explained by the careful selection of patients (with few and short strictures) receiving EBD,” as well as exclusion of patients with strictures outside the small intestine. They concluded that, “... small bowel-related EBD is an effective treatment option, and one that could be offered to more patients with Crohn’s disease in the future.”
 

‘Reassuring study’

David H. Bruining, MD, associate professor of medicine and section head of the inflammatory bowel disease interest group at Mayo Clinic, Rochester, Minn., called it a “reassuring study that confirms previous data regarding the efficacy of endoscopic balloon dilation of Crohn’s disease strictures.”

Dr. Bruining suggested in an interview that the findings, while drawn from Denmark, can be applied to a U.S. population; he also noted the “impressive” size of the study, as well the duration of follow-up, which extended up to 19 years.

EBD is “gaining more traction,” Dr. Bruining said, “as far as the belief among both referring physicians, and gastroenterologists, that it is effective, and it is safe. I think that body of literature is growing, and it’s more widely established at this point.”

Dr. Bruining noted that EBD should be reserved for patients who have short strictures no longer than 4-5 mm “without associated internal penetrating disease.”

In the future, such patients may have even more treatment options, Dr. Bruining predicted. New antifibrotic medications are “on the horizon,” which could one day be used with or without EBD to address fibrotic strictures in Crohn’s disease. Dr. Bruining is a part of the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium, a group that aims to develop this emerging approach. He and his colleagues recently published a review of research into antifibrotic therapy to date.


 

Limiting factors

“This is an important study that really adds something to the literature,” noted Joseph Carmichael, MD, chief medical officer and chief of colon and rectal surgery at the University of California, Irvine. “The cohort is a little unusual in this area in that it encompasses a whole country. Yet this is exactly what makes the data stand apart from previous studies, since the patient population was unselected. That’s how you get a true incidence of the intervention.”

Beyond the generally favorable outcomes associated with EBD, Dr. Carmichael highlighted similar rates of success across both primary and postsurgical strictures. “Some of the previous data suggest postsurgical strictures don’t do as well with endoscopic dilation, and this [study] seems to go against that,” he said. “Which really deserves a closer look.”

Reflecting on the researchers’ call for more frequent use of EBD in patients with Crohn’s disease, Dr. Carmichael speculated that several factors may be limiting current utilization in Europe and the U.S. For one, there may not be enough interventional gastroenterologists. Also, the procedure “generally requires a high-volume provider who’s got surgical backup because these [procedures] have a 2% to 4% incidence of technical failure – including perforation or bleeding. These risks may deter patients from undergoing the procedure.

“Patients with Crohn’s disease can be pretty remarkable in their ability to endure obstruction,” he added. “If someone’s feeling their symptoms aren’t altering their quality of life, they may choose not to proceed with it.”

With all candidate patients, Dr. Carmichael recommended discussing the risks of EBD compared with the risks of declining the intervention, such as complete bowel obstruction, bowel perforation, or fistula. “That’s a question that needs to be included with every conversation when we discuss procedures,” he explained.

The researchers report that, among others, they have relationships with Janssen-Cilag, AbbVie A/S, and Celgene. Dr. Bruining and Dr. Carmichael reports no relevant conflicts of interest.

This article was updated 7/29/22.

Endoscopic balloon dilation (EBD) is an effective treatment option for strictures of the small bowel in patients with Crohn’s disease, based on a nationwide Danish cohort study.

Approximately three out of four patients who underwent an EBD were spared subsequent small bowel surgery. Similar outcomes were seen across primary and postsurgical strictures, reported lead author Mads Damsgaard Wewer, BSc, of the University of Copenhagen, and colleagues.

“Retrospective studies investigating EBD are available with variable follow-up periods; however, a nationwide study to demonstrate more precise durability of EBD in unselected patients is lacking,” the investigators wrote in European Journal of Gastroenterology & Hepatology. Their aim was to understand the use of EBD and the need for redilation and surgery. This retrospective study used a cohort of adult patients with Crohn’s disease who had strictures of the small bowel during a 19-year period.

The population comprised 9,737 patients with incident Crohn’s disease, among whom 90 (1%) underwent EBD during a median 8.2-year follow-up period. Of these 90 patients, 49 had primary strictures, while the remaining 41 had postsurgical strictures.

In the primary stricture group, 59% of patients had one EBD procedure and did not require subsequent small bowel surgery, 14% of patients required redilation but no further surgery, and 27% of patients required small bowel surgery after dilation. In this same group, the 1-, 3-, and 5-year cumulative incidence rates of EBD failure were 19%, 21%, and 25%, respectively. Of note, just 8% of patients with primary stricture who were treated with EBD ultimately required enterotomy, compared with 16% of patients with primary stricture who underwent small bowel resection without first attempting EBD.

In the postsurgical stricture group, 49% of patients underwent one EBD procedure without need for another small bowel surgery, 27% needed redilation but avoided surgery, and 24% required surgery after dilation. One-, three-, and five-year cumulative incidence rates of EBD failure in this group trended slightly higher than the primary stricture group over time, at 19%, 25%, and 29%, respectively.

The researchers noted that 25% of patients required small bowel surgery after EBD, which falls below rates of 29% to 33% reported by recent studies. They explained that this edge may be “partly explained by the careful selection of patients (with few and short strictures) receiving EBD,” as well as exclusion of patients with strictures outside the small intestine. They concluded that, “... small bowel-related EBD is an effective treatment option, and one that could be offered to more patients with Crohn’s disease in the future.”
 

‘Reassuring study’

David H. Bruining, MD, associate professor of medicine and section head of the inflammatory bowel disease interest group at Mayo Clinic, Rochester, Minn., called it a “reassuring study that confirms previous data regarding the efficacy of endoscopic balloon dilation of Crohn’s disease strictures.”

Dr. Bruining suggested in an interview that the findings, while drawn from Denmark, can be applied to a U.S. population; he also noted the “impressive” size of the study, as well the duration of follow-up, which extended up to 19 years.

EBD is “gaining more traction,” Dr. Bruining said, “as far as the belief among both referring physicians, and gastroenterologists, that it is effective, and it is safe. I think that body of literature is growing, and it’s more widely established at this point.”

Dr. Bruining noted that EBD should be reserved for patients who have short strictures no longer than 4-5 mm “without associated internal penetrating disease.”

In the future, such patients may have even more treatment options, Dr. Bruining predicted. New antifibrotic medications are “on the horizon,” which could one day be used with or without EBD to address fibrotic strictures in Crohn’s disease. Dr. Bruining is a part of the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium, a group that aims to develop this emerging approach. He and his colleagues recently published a review of research into antifibrotic therapy to date.


 

Limiting factors

“This is an important study that really adds something to the literature,” noted Joseph Carmichael, MD, chief medical officer and chief of colon and rectal surgery at the University of California, Irvine. “The cohort is a little unusual in this area in that it encompasses a whole country. Yet this is exactly what makes the data stand apart from previous studies, since the patient population was unselected. That’s how you get a true incidence of the intervention.”

Beyond the generally favorable outcomes associated with EBD, Dr. Carmichael highlighted similar rates of success across both primary and postsurgical strictures. “Some of the previous data suggest postsurgical strictures don’t do as well with endoscopic dilation, and this [study] seems to go against that,” he said. “Which really deserves a closer look.”

Reflecting on the researchers’ call for more frequent use of EBD in patients with Crohn’s disease, Dr. Carmichael speculated that several factors may be limiting current utilization in Europe and the U.S. For one, there may not be enough interventional gastroenterologists. Also, the procedure “generally requires a high-volume provider who’s got surgical backup because these [procedures] have a 2% to 4% incidence of technical failure – including perforation or bleeding. These risks may deter patients from undergoing the procedure.

“Patients with Crohn’s disease can be pretty remarkable in their ability to endure obstruction,” he added. “If someone’s feeling their symptoms aren’t altering their quality of life, they may choose not to proceed with it.”

With all candidate patients, Dr. Carmichael recommended discussing the risks of EBD compared with the risks of declining the intervention, such as complete bowel obstruction, bowel perforation, or fistula. “That’s a question that needs to be included with every conversation when we discuss procedures,” he explained.

The researchers report that, among others, they have relationships with Janssen-Cilag, AbbVie A/S, and Celgene. Dr. Bruining and Dr. Carmichael reports no relevant conflicts of interest.

This article was updated 7/29/22.

Choice of biologic therapy in the first line and later may impact long-term outcomes in patients with perianal Crohn’s disease (pCD), according to a retrospective study.

John Gubatan, MD, of Stanford (Calif.) University, and colleagues reported that, compared with no biologic therapy, first-line treatment with an anti–tumor necrosis factor (TNF) agent or ustekinumab significantly reduced risk of perianal abscess recurrence at 5 years, whereas vedolizumab offered no such benefit. After failure of the initial anti-TNF, switching to another anti-TNF agent is the most effective option.

“Although pCD is recognized to be an aggressive phenotype, data on whether escalating to a biologic at the time of perianal disease diagnosis may alter the natural history and long-term clinical outcomes of pCD is limited,” the researchers wrote in Journal of Clinical Gastroenterology. “This is the first study to explore how the type of biologic therapy at the time of perianal disease diagnosis and change in biologic therapy after first anti-TNF failure are associated with rates of long-term clinical outcomes.”

The study included 311 patients with pCD treated at Stanford University from 1998 to 2020. At the time of diagnosis, 168 of these patients started a biologic, most often an anti-TNF agent (n = 138), followed distantly by ustekinumab (n = 16) or vedolizumab (n = 14). Efficacy of these first-line biologics was compared with no biologic therapy in terms of five clinical outcomes at 5 years: surgical intervention, colectomy, permanent diversion, fistula closure, and perianal abscess recurrence.

Although both reduced risk of perianal abscess recurrence, it was still higher with anti-TNF therapy (hazard ratio, 0.48; 95% confidence interval, 0.32-0.74) than with ustekinumab (HR, 0.20; 95% CI, 0.07-0.56). Ustekinumab also increased the rate of perianal fistula closure by more than threefold (HR, 3.58; 95% CI, 1.04-12.35).

Vedolizumab, on the other hand, offered no significant benefit across any of the five outcomes.

None of the biologics had an impact on rates of surgical intervention, colectomy, or permanent diversion.

Further analyses explored the long-term effects of second-line biologic choice after initial failure with anti-TNF therapy. Switching to another anti-TNF agent was more effective than switching to ustekinumab at reducing risks of colectomy (HR, 0.20; 95% CI, 0.04-0.90) and permanent diversion (HR, 0.16; 95% CI, 0.03-0.94); switching to ustekinumab was more effective than switching to vedolizumab for perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96).

Switching to another anti-TNF biologic or ustekinumab may be associated with better 5-year outcomes, compared with switching to vedolizumab in patients with pCD, according to Dr. Gubatan. Other guidelines or data that might steer this sequencing decision are scant. However, the findings should be validated with prospective data, ideally from head-to-head trials.

Jordan E. Axelrad, MD, of NYU Langone Health, New York, said the present study is noteworthy for addressing a “very-difficult-to-treat condition that has limited data as well as very limited long-term outcome data for our currently available interventions.”

Dr. Axelrad appreciated how the study focused on the distribution of clinical manifestations of pCD, including ulcers (10%), fissures (23.2%), abscesses (76.1%), and fistulas (84.2%). According to Dr. Axelrad, the efficacy data provide really important insights for clinicians who choose biologic therapies. He noted that, in the absence of head-to-head clinical trials, “it’s absolutely important that we use these results to help us guide therapy” for patients with pCD.

While the biologics included in the study were efficacious to varying degrees, Dr. Axelrad pointed out that no choice was associated with a reduced risk of surgical intervention. “That really underscored for me how complex this patient population is,” he said. “Despite good medical therapies … we’re still not necessarily making a huge dent in the risk of surgical intervention requirements for this complex patient group.”

Dr. Gubatan disclosed support from a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a National Institutes of Health NIDDK LRP Award, and a Doris Duke Physician Scientist Fellowship Award; his colleagues reported no conflicts of interest. Dr. Axelrad reports relationships with Janssen, AbbVie, Pfizer, and others.

Choice of biologic therapy in the first line and later may impact long-term outcomes in patients with perianal Crohn’s disease (pCD), according to a retrospective study.

John Gubatan, MD, of Stanford (Calif.) University, and colleagues reported that, compared with no biologic therapy, first-line treatment with an anti–tumor necrosis factor (TNF) agent or ustekinumab significantly reduced risk of perianal abscess recurrence at 5 years, whereas vedolizumab offered no such benefit. After failure of the initial anti-TNF, switching to another anti-TNF agent is the most effective option.

“Although pCD is recognized to be an aggressive phenotype, data on whether escalating to a biologic at the time of perianal disease diagnosis may alter the natural history and long-term clinical outcomes of pCD is limited,” the researchers wrote in Journal of Clinical Gastroenterology. “This is the first study to explore how the type of biologic therapy at the time of perianal disease diagnosis and change in biologic therapy after first anti-TNF failure are associated with rates of long-term clinical outcomes.”

The study included 311 patients with pCD treated at Stanford University from 1998 to 2020. At the time of diagnosis, 168 of these patients started a biologic, most often an anti-TNF agent (n = 138), followed distantly by ustekinumab (n = 16) or vedolizumab (n = 14). Efficacy of these first-line biologics was compared with no biologic therapy in terms of five clinical outcomes at 5 years: surgical intervention, colectomy, permanent diversion, fistula closure, and perianal abscess recurrence.

Although both reduced risk of perianal abscess recurrence, it was still higher with anti-TNF therapy (hazard ratio, 0.48; 95% confidence interval, 0.32-0.74) than with ustekinumab (HR, 0.20; 95% CI, 0.07-0.56). Ustekinumab also increased the rate of perianal fistula closure by more than threefold (HR, 3.58; 95% CI, 1.04-12.35).

Vedolizumab, on the other hand, offered no significant benefit across any of the five outcomes.

None of the biologics had an impact on rates of surgical intervention, colectomy, or permanent diversion.

Further analyses explored the long-term effects of second-line biologic choice after initial failure with anti-TNF therapy. Switching to another anti-TNF agent was more effective than switching to ustekinumab at reducing risks of colectomy (HR, 0.20; 95% CI, 0.04-0.90) and permanent diversion (HR, 0.16; 95% CI, 0.03-0.94); switching to ustekinumab was more effective than switching to vedolizumab for perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96).

Switching to another anti-TNF biologic or ustekinumab may be associated with better 5-year outcomes, compared with switching to vedolizumab in patients with pCD, according to Dr. Gubatan. Other guidelines or data that might steer this sequencing decision are scant. However, the findings should be validated with prospective data, ideally from head-to-head trials.

Jordan E. Axelrad, MD, of NYU Langone Health, New York, said the present study is noteworthy for addressing a “very-difficult-to-treat condition that has limited data as well as very limited long-term outcome data for our currently available interventions.”

Dr. Axelrad appreciated how the study focused on the distribution of clinical manifestations of pCD, including ulcers (10%), fissures (23.2%), abscesses (76.1%), and fistulas (84.2%). According to Dr. Axelrad, the efficacy data provide really important insights for clinicians who choose biologic therapies. He noted that, in the absence of head-to-head clinical trials, “it’s absolutely important that we use these results to help us guide therapy” for patients with pCD.

While the biologics included in the study were efficacious to varying degrees, Dr. Axelrad pointed out that no choice was associated with a reduced risk of surgical intervention. “That really underscored for me how complex this patient population is,” he said. “Despite good medical therapies … we’re still not necessarily making a huge dent in the risk of surgical intervention requirements for this complex patient group.”

Dr. Gubatan disclosed support from a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a National Institutes of Health NIDDK LRP Award, and a Doris Duke Physician Scientist Fellowship Award; his colleagues reported no conflicts of interest. Dr. Axelrad reports relationships with Janssen, AbbVie, Pfizer, and others.

Choice of biologic therapy in the first line and later may impact long-term outcomes in patients with perianal Crohn’s disease (pCD), according to a retrospective study.

John Gubatan, MD, of Stanford (Calif.) University, and colleagues reported that, compared with no biologic therapy, first-line treatment with an anti–tumor necrosis factor (TNF) agent or ustekinumab significantly reduced risk of perianal abscess recurrence at 5 years, whereas vedolizumab offered no such benefit. After failure of the initial anti-TNF, switching to another anti-TNF agent is the most effective option.

“Although pCD is recognized to be an aggressive phenotype, data on whether escalating to a biologic at the time of perianal disease diagnosis may alter the natural history and long-term clinical outcomes of pCD is limited,” the researchers wrote in Journal of Clinical Gastroenterology. “This is the first study to explore how the type of biologic therapy at the time of perianal disease diagnosis and change in biologic therapy after first anti-TNF failure are associated with rates of long-term clinical outcomes.”

The study included 311 patients with pCD treated at Stanford University from 1998 to 2020. At the time of diagnosis, 168 of these patients started a biologic, most often an anti-TNF agent (n = 138), followed distantly by ustekinumab (n = 16) or vedolizumab (n = 14). Efficacy of these first-line biologics was compared with no biologic therapy in terms of five clinical outcomes at 5 years: surgical intervention, colectomy, permanent diversion, fistula closure, and perianal abscess recurrence.

Although both reduced risk of perianal abscess recurrence, it was still higher with anti-TNF therapy (hazard ratio, 0.48; 95% confidence interval, 0.32-0.74) than with ustekinumab (HR, 0.20; 95% CI, 0.07-0.56). Ustekinumab also increased the rate of perianal fistula closure by more than threefold (HR, 3.58; 95% CI, 1.04-12.35).

Vedolizumab, on the other hand, offered no significant benefit across any of the five outcomes.

None of the biologics had an impact on rates of surgical intervention, colectomy, or permanent diversion.

Further analyses explored the long-term effects of second-line biologic choice after initial failure with anti-TNF therapy. Switching to another anti-TNF agent was more effective than switching to ustekinumab at reducing risks of colectomy (HR, 0.20; 95% CI, 0.04-0.90) and permanent diversion (HR, 0.16; 95% CI, 0.03-0.94); switching to ustekinumab was more effective than switching to vedolizumab for perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96).

Switching to another anti-TNF biologic or ustekinumab may be associated with better 5-year outcomes, compared with switching to vedolizumab in patients with pCD, according to Dr. Gubatan. Other guidelines or data that might steer this sequencing decision are scant. However, the findings should be validated with prospective data, ideally from head-to-head trials.

Jordan E. Axelrad, MD, of NYU Langone Health, New York, said the present study is noteworthy for addressing a “very-difficult-to-treat condition that has limited data as well as very limited long-term outcome data for our currently available interventions.”

Dr. Axelrad appreciated how the study focused on the distribution of clinical manifestations of pCD, including ulcers (10%), fissures (23.2%), abscesses (76.1%), and fistulas (84.2%). According to Dr. Axelrad, the efficacy data provide really important insights for clinicians who choose biologic therapies. He noted that, in the absence of head-to-head clinical trials, “it’s absolutely important that we use these results to help us guide therapy” for patients with pCD.

While the biologics included in the study were efficacious to varying degrees, Dr. Axelrad pointed out that no choice was associated with a reduced risk of surgical intervention. “That really underscored for me how complex this patient population is,” he said. “Despite good medical therapies … we’re still not necessarily making a huge dent in the risk of surgical intervention requirements for this complex patient group.”

Dr. Gubatan disclosed support from a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a National Institutes of Health NIDDK LRP Award, and a Doris Duke Physician Scientist Fellowship Award; his colleagues reported no conflicts of interest. Dr. Axelrad reports relationships with Janssen, AbbVie, Pfizer, and others.

Use of new biologics such as ustekinumab and vedolizumab during pregnancy appears to be safe, with favorable pregnancy and postnatal infant outcomes, according to a study published in the Journal of Crohn’s and Colitis.

The results, which come from the Czech IBD Working Group, point to the need for safe options to treat inflammatory bowel disease (IBD) during pregnancy, wrote the researchers led by Katarina Mitrova, MD, PhD, of the Clinical and Research Centre for Inflammatory Bowel Disease at Charles University, Prague.

digitalskillet/Thinkstock

“As the long-term therapy can affect pregnancy and neonatal outcomes, strong evidence is needed to reassure patients about safety,” they wrote. “Recent years have seen significant progress in research around anti-TNF treatment in pregnancy, confirming its safe use, but the data on the new biologics are still limited.”

In a prospective, multicenter observational study of women with IBD, the researchers included 54 pregnancies in 49 women exposed to ustekinumab and 39 pregnancies in 37 women exposed to vedolizumab 2 months prior to conception or during pregnancy between January 2017 and December 2021 in 15 centers across the Czech Republic.

The control group of 90 pregnancies in 81 women was collected retrospectively and included pregnant women with IBD exposed to anti–tumor necrosis factor (TNF) therapy – 29% to adalimumab and 71% to infliximab – in two centers in the Czech Republic between 2013 and 2021. Only singleton pregnancies were included in the analyses because of the increased risk of complications in multiple pregnancies, the investigators noted.

About 94% of patients treated with ustekinumab had Crohn’s disease, while the disease distribution was nearly equal in patients treated with vedolizumab. Active disease any time during pregnancy was reported in 17% of women on ustekinumab and 23% of those on vedolizumab, as well as 10% of those on anti-TNF therapy.

Pregnancies resulted in live births in 79.9% of the ustekinumab group, 89.7% of the vedolizumab group, and 87.8% of the anti-TNF group; however, these differences were not statistically significant.

Overall, there were no significant differences in pregnancy outcomes between either the vedolizumab or ustekinumab groups or the controls. Similarly, there were no negative safety signals in the postnatal outcomes of children up to 1 year of life, including measures such as growth, psychomotor development, and the risk of allergy, atopy, or infectious complications.

Blue Planet Studio/Getty Images

Ustekinumab was administered for the last time during pregnancy at median gestational week 33, ranging from 18 to 38 weeks. Five women stopped the treatment during the second trimester, and 37 continued to use it during the third trimester. An intensified regimen, shortening the interval to 4-6 weeks, was given to 13 patients. There were no disease flares after stopping the treatment.

Vedolizumab was administered for the last time during pregnancy at median gestational week 32, ranging from 18 to 38 weeks. Seven women discontinued the treatment during the second trimester, and 27 continued to use it in the third trimester. An intensified regimen was used in six pregnancies. No disease relapse was observed after treatment discontinuation.

Of the pregnancies that resulted in live births, maternal pregnancy-related complications occurred in six women (14%) treated with ustekinumab and seven women (20%) treated with vedolizumab. The most frequent complication was gestational diabetes mellitus, followed by arterial hypertension, preeclampsia, and intrapartum hemorrhage. The rate of complications was not significantly different from the control population for either biologic.

On the day of delivery, maternal venous blood and umbilical cord blood were collected to determine the levels of ustekinumab and vedolizumab.

Additional studies are needed because of the overall small study population, the researchers suggested.

“According to recent guidelines, continuing with biologic therapy, including new biologics, is recommended throughout pregnancy to prevent disease relapse, which is a strong risk factor of adverse pregnancy outcomes,” the researchers wrote.

“Data on the safety of non-anti-TNF biologics in pregnancy are limited by small numbers and, in many cases, retrospective design,” said Eugenia Shmidt, MD, an assistant professor in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota and founder of the university's IBD Preconception and Pregnancy Planning Clinic. “This study’s prospective nature and larger size make it a particularly valuable contribution to the field. Hopefully IBD clinicians will be reassured that ustekinumab and vedolizumab are safe for both mother and baby and can be continued throughout the entire duration of pregnancy.”

No specific funding was received for the study. The authors listed financial disclosures and conflict of interest statements for AbbVie, Takeda, Janssen, Pfizer, Biogen, Tillotts, Ferring, Alfasigma, Celltrion, and PRO.MED.CS. Dr. Shmidt declared no relevant disclosures.

This article was updated July 18, 2022.

Use of new biologics such as ustekinumab and vedolizumab during pregnancy appears to be safe, with favorable pregnancy and postnatal infant outcomes, according to a study published in the Journal of Crohn’s and Colitis.

The results, which come from the Czech IBD Working Group, point to the need for safe options to treat inflammatory bowel disease (IBD) during pregnancy, wrote the researchers led by Katarina Mitrova, MD, PhD, of the Clinical and Research Centre for Inflammatory Bowel Disease at Charles University, Prague.

digitalskillet/Thinkstock

“As the long-term therapy can affect pregnancy and neonatal outcomes, strong evidence is needed to reassure patients about safety,” they wrote. “Recent years have seen significant progress in research around anti-TNF treatment in pregnancy, confirming its safe use, but the data on the new biologics are still limited.”

In a prospective, multicenter observational study of women with IBD, the researchers included 54 pregnancies in 49 women exposed to ustekinumab and 39 pregnancies in 37 women exposed to vedolizumab 2 months prior to conception or during pregnancy between January 2017 and December 2021 in 15 centers across the Czech Republic.

The control group of 90 pregnancies in 81 women was collected retrospectively and included pregnant women with IBD exposed to anti–tumor necrosis factor (TNF) therapy – 29% to adalimumab and 71% to infliximab – in two centers in the Czech Republic between 2013 and 2021. Only singleton pregnancies were included in the analyses because of the increased risk of complications in multiple pregnancies, the investigators noted.

About 94% of patients treated with ustekinumab had Crohn’s disease, while the disease distribution was nearly equal in patients treated with vedolizumab. Active disease any time during pregnancy was reported in 17% of women on ustekinumab and 23% of those on vedolizumab, as well as 10% of those on anti-TNF therapy.

Pregnancies resulted in live births in 79.9% of the ustekinumab group, 89.7% of the vedolizumab group, and 87.8% of the anti-TNF group; however, these differences were not statistically significant.

Overall, there were no significant differences in pregnancy outcomes between either the vedolizumab or ustekinumab groups or the controls. Similarly, there were no negative safety signals in the postnatal outcomes of children up to 1 year of life, including measures such as growth, psychomotor development, and the risk of allergy, atopy, or infectious complications.

Blue Planet Studio/Getty Images

Ustekinumab was administered for the last time during pregnancy at median gestational week 33, ranging from 18 to 38 weeks. Five women stopped the treatment during the second trimester, and 37 continued to use it during the third trimester. An intensified regimen, shortening the interval to 4-6 weeks, was given to 13 patients. There were no disease flares after stopping the treatment.

Vedolizumab was administered for the last time during pregnancy at median gestational week 32, ranging from 18 to 38 weeks. Seven women discontinued the treatment during the second trimester, and 27 continued to use it in the third trimester. An intensified regimen was used in six pregnancies. No disease relapse was observed after treatment discontinuation.

Of the pregnancies that resulted in live births, maternal pregnancy-related complications occurred in six women (14%) treated with ustekinumab and seven women (20%) treated with vedolizumab. The most frequent complication was gestational diabetes mellitus, followed by arterial hypertension, preeclampsia, and intrapartum hemorrhage. The rate of complications was not significantly different from the control population for either biologic.

On the day of delivery, maternal venous blood and umbilical cord blood were collected to determine the levels of ustekinumab and vedolizumab.

Additional studies are needed because of the overall small study population, the researchers suggested.

“According to recent guidelines, continuing with biologic therapy, including new biologics, is recommended throughout pregnancy to prevent disease relapse, which is a strong risk factor of adverse pregnancy outcomes,” the researchers wrote.

“Data on the safety of non-anti-TNF biologics in pregnancy are limited by small numbers and, in many cases, retrospective design,” said Eugenia Shmidt, MD, an assistant professor in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota and founder of the university's IBD Preconception and Pregnancy Planning Clinic. “This study’s prospective nature and larger size make it a particularly valuable contribution to the field. Hopefully IBD clinicians will be reassured that ustekinumab and vedolizumab are safe for both mother and baby and can be continued throughout the entire duration of pregnancy.”

No specific funding was received for the study. The authors listed financial disclosures and conflict of interest statements for AbbVie, Takeda, Janssen, Pfizer, Biogen, Tillotts, Ferring, Alfasigma, Celltrion, and PRO.MED.CS. Dr. Shmidt declared no relevant disclosures.

This article was updated July 18, 2022.

Use of new biologics such as ustekinumab and vedolizumab during pregnancy appears to be safe, with favorable pregnancy and postnatal infant outcomes, according to a study published in the Journal of Crohn’s and Colitis.

The results, which come from the Czech IBD Working Group, point to the need for safe options to treat inflammatory bowel disease (IBD) during pregnancy, wrote the researchers led by Katarina Mitrova, MD, PhD, of the Clinical and Research Centre for Inflammatory Bowel Disease at Charles University, Prague.

digitalskillet/Thinkstock

“As the long-term therapy can affect pregnancy and neonatal outcomes, strong evidence is needed to reassure patients about safety,” they wrote. “Recent years have seen significant progress in research around anti-TNF treatment in pregnancy, confirming its safe use, but the data on the new biologics are still limited.”

In a prospective, multicenter observational study of women with IBD, the researchers included 54 pregnancies in 49 women exposed to ustekinumab and 39 pregnancies in 37 women exposed to vedolizumab 2 months prior to conception or during pregnancy between January 2017 and December 2021 in 15 centers across the Czech Republic.

The control group of 90 pregnancies in 81 women was collected retrospectively and included pregnant women with IBD exposed to anti–tumor necrosis factor (TNF) therapy – 29% to adalimumab and 71% to infliximab – in two centers in the Czech Republic between 2013 and 2021. Only singleton pregnancies were included in the analyses because of the increased risk of complications in multiple pregnancies, the investigators noted.

About 94% of patients treated with ustekinumab had Crohn’s disease, while the disease distribution was nearly equal in patients treated with vedolizumab. Active disease any time during pregnancy was reported in 17% of women on ustekinumab and 23% of those on vedolizumab, as well as 10% of those on anti-TNF therapy.

Pregnancies resulted in live births in 79.9% of the ustekinumab group, 89.7% of the vedolizumab group, and 87.8% of the anti-TNF group; however, these differences were not statistically significant.

Overall, there were no significant differences in pregnancy outcomes between either the vedolizumab or ustekinumab groups or the controls. Similarly, there were no negative safety signals in the postnatal outcomes of children up to 1 year of life, including measures such as growth, psychomotor development, and the risk of allergy, atopy, or infectious complications.

Blue Planet Studio/Getty Images

Ustekinumab was administered for the last time during pregnancy at median gestational week 33, ranging from 18 to 38 weeks. Five women stopped the treatment during the second trimester, and 37 continued to use it during the third trimester. An intensified regimen, shortening the interval to 4-6 weeks, was given to 13 patients. There were no disease flares after stopping the treatment.

Vedolizumab was administered for the last time during pregnancy at median gestational week 32, ranging from 18 to 38 weeks. Seven women discontinued the treatment during the second trimester, and 27 continued to use it in the third trimester. An intensified regimen was used in six pregnancies. No disease relapse was observed after treatment discontinuation.

Of the pregnancies that resulted in live births, maternal pregnancy-related complications occurred in six women (14%) treated with ustekinumab and seven women (20%) treated with vedolizumab. The most frequent complication was gestational diabetes mellitus, followed by arterial hypertension, preeclampsia, and intrapartum hemorrhage. The rate of complications was not significantly different from the control population for either biologic.

On the day of delivery, maternal venous blood and umbilical cord blood were collected to determine the levels of ustekinumab and vedolizumab.

Additional studies are needed because of the overall small study population, the researchers suggested.

“According to recent guidelines, continuing with biologic therapy, including new biologics, is recommended throughout pregnancy to prevent disease relapse, which is a strong risk factor of adverse pregnancy outcomes,” the researchers wrote.

“Data on the safety of non-anti-TNF biologics in pregnancy are limited by small numbers and, in many cases, retrospective design,” said Eugenia Shmidt, MD, an assistant professor in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota and founder of the university's IBD Preconception and Pregnancy Planning Clinic. “This study’s prospective nature and larger size make it a particularly valuable contribution to the field. Hopefully IBD clinicians will be reassured that ustekinumab and vedolizumab are safe for both mother and baby and can be continued throughout the entire duration of pregnancy.”

No specific funding was received for the study. The authors listed financial disclosures and conflict of interest statements for AbbVie, Takeda, Janssen, Pfizer, Biogen, Tillotts, Ferring, Alfasigma, Celltrion, and PRO.MED.CS. Dr. Shmidt declared no relevant disclosures.

This article was updated July 18, 2022.

When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.

Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.

However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.

“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.

The research was published online by Clinical Gastroenterology and Hepatology.
 

Real-world evidence

“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.

They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”

“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”

The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.

While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”

To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.

They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.

Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.

There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
 

Early difference fades

Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.

Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.

Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.

The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.

Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.

The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.

But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.

“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
 

‘Interesting’ efficacy data

Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.

“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.

While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.

“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”

The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”

Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.

“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.

Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.

The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.

A version of this article first appeared on Medscape.com.

When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.

Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.

However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.

“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.

The research was published online by Clinical Gastroenterology and Hepatology.
 

Real-world evidence

“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.

They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”

“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”

The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.

While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”

To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.

They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.

Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.

There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
 

Early difference fades

Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.

Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.

Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.

The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.

Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.

The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.

But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.

“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
 

‘Interesting’ efficacy data

Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.

“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.

While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.

“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”

The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”

Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.

“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.

Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.

The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.

A version of this article first appeared on Medscape.com.

When anti–tumor necrosis factor-alpha (anti-TNF) treatment fails to achieve remission for patients with ulcerative colitis (UC), tofacitinib (Xeljanz) appears more effect sooner than vedolizumab (Entyvio), suggests a Dutch registry study.

Data on nearly 150 patients with UC who had already undergone treatment with anti-TNF drugs showed that combined clinical and biochemical remission was about five times more likely with tofacitinib versus vedolizumab within 12 weeks of starting therapy.

However, the differences tailed off over subsequent weeks, such that there was no significant difference in combined remission rates at 52 weeks. There were also no notable differences in safety between the two drugs.

“These results may help in guiding clinical decisionmaking after anti-TNF failure in patients with UC,” the authors write.

The research was published online by Clinical Gastroenterology and Hepatology.
 

Real-world evidence

“This study offers more real-world evidence than a standard randomized controlled trial, since there was no randomization between the two study groups and no strict inclusion and exclusion criteria,” co–senior authors Tessa Straatmijer, MD, PhD candidate, and Marjolijn Duijvestein, MD, Amsterdam University Medical Center, the Netherlands, told this news organization.

They continued: “It is known that tofacitinib is more rapid of action compared to vedolizumab. We therefore expected that the odds ratio of remission rates between the two groups would be higher at weeks 12 and 24, compared to week 52.”

“We will continue with collecting data in our prospective cohort up to 10 years after initiating tofacitinib or vedolizumab,” Dr. Straatmijer and Dr. Duijvestein added. “Hopefully we can provide long-term outcomes after a couple of years.”

The authors highlight that for a “considerable proportion” of patients with UC, their condition does not respond to anti-TNF drugs, they experience adverse effects, or the response diminishes over time. Alternatives, such as vedolizumab and tofacitinib, are typically “prescribed after failure of the anti-TNF,” owing to their price and clinician experience.

While vedolizumab (an α4β7 integrin blocker) and tofacitinib (a Janus kinase inhibitor) have different mechanisms of action, head-to-head randomized controlled trials comparing their efficacy among patients with UC whose condition is refractory to anti-TNF are “lacking,” they add. “However, to guide physician decisionmaking on the most suitable drug choice after anti-TNF failure, effectiveness data comparing tofacitinib with vedolizumab is pivotal.”

To assess the comparative effectiveness and safety of the next therapeutic options, the team examined data from the Dutch Initiative on Crohn and Colitis registry.

They identified nearly 300 adult patients with clinical or biochemical disease activity who had initiated treatment with vedolizumab or tofacitinib. They excluded patients without prior anti-TNF treatment, those who had previously been treated with vedolizumab or tofacitinib, and those who did not have clinical and biochemical or endoscopic disease activity at baseline. The final analysis included 83 patients given vedolizumab and 65 treated with tofacitinib.

Patients given tofacitinib received 10 mg twice daily for the first 8 weeks, followed by maintenance treatment of 5 mg twice daily, with optional dose optimization in case of insufficient response. Vedolizumab was administered intravenously in line with the label; 300 mg was administered at weeks 0, 2, and 6, followed by 300 mg every 8 weeks, with a shortened infusion interval in cases of inadequate response.

There were few differences between the two groups at baseline, although patients given vedolizumab had been treated longer than those in the tofacitinib group (12 years vs. 7 years). Vedolizumab patients were also more likely to be receiving concomitant oral prednisone at baseline (50.6% vs. 30.8%).
 

Early difference fades

Corticosteroid-free clinical remission at week 12 was observed in 27.7% of patients in the vedolizumab group, rising to 38.6% at week 24 and 37.3% at week 52. Among those given tofacitinib, the rates of clinical remission were 56.9% at week 12, 60.0% at week 24, and 55.4% at week 52.

Propensity score-weight analysis revealed that tofacitinib patients were more likely to achieve corticosteroid-free clinical remission at weeks 12, 24, and 52, compared with those given vedolizumab, at odds ratio of 6.33, 3.02, and 1.86, respectively.

Biochemical remission rates among patients treated with vedolizumab were 25.3% at week 12, 28.9% at week 24, and 22.9% at week 52. For the tofacitinib group, the rates were 40.0%, 36.9%, and 27.7%, respectively. Biochemical remission was defined by C-reactive protein or fecal calprotectin levels.

The likelihood of biochemical remission was again greater with tofacitinib than with vedolizumab, at an odds ratio of 3.27 at week 12, 1.87 at week 24, and 1.81 at week 52.

Combined clinical and biochemical remission was more likely among patients given tofacitinib versus vedolizumab at week 12, at an odds ratio of 5.05, and at week 24, at an odds ratio of 2.11. However, at week 52, the difference was no longer significant, at an odds ratio of 1.17.

The authors note that there was no difference in the rate of infection between the two treatment groups, and the rate of severe adverse events was similar. However, three patients receiving tofacitinib experienced herpes simplex infections, compared with none of those given vedolizumab.

But, compared with the tofacitinib group, patients taking vedolizumab were more likely to discontinue treatment before 52 weeks, primarily because of a lack of response to treatment.

“The present study underlines that both vedolizumab and tofacitinib are relatively safe treatment options in patients with UC in a 12-month period,” the team writes.
 

‘Interesting’ efficacy data

Approached for comment, Alan C. Moss, MD, a professor of gastroenterology at Boston University School of Medicine, said that the findings are “interesting” for clinicians.

“We have so many treatment options right now, picking one over the other, particularly in patients like this who fail anti-TNF, is very important,” he told this news organization.

While he noted that registry data such as these are usually powered for “one outcome” (either efficacy or safety), “the immediate conclusions that come to mind are that certainly the efficacy of the two drugs in this patient population looks impressive.

“What we do note, though, is over time, as you get longer into the study, they start to become closer in terms of overall remission,” which Dr. Moss said fits with the current understanding that vedolizumab “takes longer to work.”

The take-away lesson from the study is that the short-term efficacy of tofacitinib is “superior,” Dr. Moss said, but, over the medium to long term, vedolizumab “may turn out to be more equivalent.”

Dr. Moss also pointed out that approximately 40% of patients given tofacitinib in the study began with the higher 10-mg twice-daily dose, “which is not the FDA-approved maintenance dose,” and over time about a quarter stayed on the higher dose.

“What that tells us is that, yes, it works faster if you’re using the higher dose, and over time, a certain proportion of these patients needed a higher dose to get these results,” he said.

Consequently, Dr. Moss said that the two treatment groups were not “equivalent” in terms of the doses given relative to normal maintenance dose.

The Initiative on Crohn and Colitis Fellowship is sponsored by AbbVie, Pfizer, Takeda, Celgene, Janssen Pharmaceutica, Teva Pharmaceutical Industries, Cablon Medical, Ferring Pharmaceuticals, Mundipharma, Dr. Falk Pharma, Sandoz, and Tramedico. Dr. Duijvestein has relationships with Echo Pharma, Robarts Clinical Trials, Janssen, Merck, Pfizer, Takeda, Tillotts Pharma, and Dr. Falk Pharma. Other authors have numerous relationships with industry. Dr. Moss has relationships with Pfizer and Janssen.

A version of this article first appeared on Medscape.com.

A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.

Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.

Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.

The study was published online in Gastroenterology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.

Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.

One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.

To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.

The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.

The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.

In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.

There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.

The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.

The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.

The researchers have no relevant financial disclosures.

A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.

Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.

Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.

The study was published online in Gastroenterology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.

Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.

One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.

To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.

The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.

The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.

In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.

There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.

The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.

The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.

The researchers have no relevant financial disclosures.

A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.

Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.

Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.

The study was published online in Gastroenterology.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.

Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.

One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.

To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.

The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.

The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.

In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.

There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.

The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.

The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.

The researchers have no relevant financial disclosures.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Fecal microbiota transplantation (FMT) resulted in sustained high response rates in patients with irritable bowel syndrome (IBS) and resulted in only mild side effects after 3 years, new data show.

Nearly three out of four people in a clinical trial experienced fewer symptoms and fatigue and a greater quality of life at both 2 years and 3 years after FMT in Norway. Those FMT-treated patients who relapsed subsequently responded to FMT upon retransplantation, reported the authors, who also correlated individual microbial profiles with clinical outcomes.

The study, led by Magdy El-Salhy, MD, PhD, department of medicine, Stord (Norway) Hospital, was published online in Gastroenterology.

An expert not involved with the study, Brian Lacy, MD, PhD, a gastroenterologist with the Mayo Clinic in Jacksonville, Fla., said that the results of the study are important, but he cautions against treating IBS with FMT outside clinical trials, at least until the protocol is validated, given demonstrated risks.

The new study included 125 patients (104 women, 21 men) in three groups: 38 received a placebo, 42 received 30 g of donor feces, and 45 received 60 g of donor feces. The feces – all from one male donor – was administered to the duodenum.

The response rates for those who received FMT were significantly higher than for those who received placebo. Those receiving 30 g of feces had a response rate of 69.1%, and those in the 60-g group had a response rate of 77.8%, whereas the response rate in the placebo group was 26.3%.

Patients provided a fecal sample and completed five questionnaires at the beginning of the study and at 2 and 3 years after FMT.

Patients in both treatment groups had significantly fewer IBS symptoms – such as abdominal pain, abdominal bloating, dissatisfaction with bowel habits, and quality-of-life interruption – and less fatigue compared with the placebo group, as well as higher quality of life scores at 2 and 3 years.

No long-term adverse effects were reported.

The dysbiosis index decreased only in the treatment group at years 2 and 3.
 

Microbial modifications correlate with IBS symptoms

In addition, the fluorescent signals of 10 bacteria that had changed after FMT were significantly correlated with improved IBS symptoms and fatigue in both treatment groups.

“Of the bacteria markers whose fluorescence signals changed in the 30-g and 60-g groups, but not in the placebo group, at both 2 and 3 years after FMT, nine were significantly correlated with the total IBS-SSS [IBS–Severity Scoring System] scores,” the authors wrote. One more bacterium with a changed fluorescence signal in the active treatment group also correlated with total fatigue.

Dr. El-Salhy told this news organization that those findings open the door for the select bacteria to be used, for example, in capsule form to treat IBS and fatigue.

The most surprising finding for the team was that the “majority of IBS patients [who] responded to FMT maintained response up to 3 years” or more, said Dr. El-Salhy, alluding to unpublished data up to 5 years.

“Furthermore, 80% of those who relapsed after 3 years responded to a new FMT,” he said.

Women had higher response rates than men at years 2 and 3 after FMT, but there were no differences between complete remission rates of women and men at years 2 and 3.
 

‘Impressive’ results, but caution warranted

“The results are impressive,” Dr. Lacy said. “I believe that this will help researchers around the world refine their techniques, as we learn more about FMT for the treatment of IBS. It also clearly plays up the importance of the gut microbiome in symptom generation in IBS patients.”

However, he said, until the results are replicated, and the protocol validated, FMT should not be used routinely to treat IBS because there are risks with the procedure.

Dr. Lacy pointed out there have been mixed results in the literature regarding FMT and IBS.

He cited a meta-analysis of four studies (n = 254) in 2019 that did not show a benefit for FMT in patients with IBS. However, a second meta-analysis of five studies (n = 267) did show some benefit, possibly owing to the type of donor and small-bowel infusion.

The authors added that, in the seven randomized, controlled trials investigating FMT for IBS, four concluded that FMT eased symptoms and improved quality of life in patients with IBS, whereas treatment was not effective in the other three.

The authors pointed to differences in protocols, donors, the cohort treated, FMT dose, and route of administration.

The longest response time previously studied in the randomized, controlled trials was 1 year, the authors pointed out. The new study was a 3-year follow-up of these authors’ previous randomly assigned placebo-controlled trial participants.
 

The ‘super-donor’ concept

The authors of the current study described the single chosen donor as “a healthy male aged 36 years with a normal BMI [body mass index] who was born via vaginal delivery, breastfed, a nonsmoker, was not taking any medication, was treated only a few times with antibiotics, exercised regularly, and consumed a sport-specific diet that was richer in protein, fiber, minerals, and vitamins than the average diet.”

The donor had high microbial diversity, and his fecal bacteria makeup was different from that of 254 healthy subjects for 14 of the 48 bacterial markers investigators tested.

Dr. Lacy said that the “super-donor” concept is noteworthy and an apparent key to success.

“Other studies have not done this,” Dr. Lacy noted.

Among the strengths of the study are that it included a relatively large cohort of patients with IBS, with three IBS subtypes and a single well-defined donor. However, it did not include the fourth IBS subtype, unsubtyped IBS, and it only investigated a part of the intestinal bacterial content, the authors acknowledged.

Most interesting, Dr. Lacy said, is that the IBS subtype did not seem to matter to FMT outcomes at 3 years and that all three subtypes responded better than placebo.

“That’s encouraging,” Dr. Lacy said.

The investigators received a grant from Helse Fonna. The study authors and Dr. Lacy reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Fecal microbiota transplantation (FMT) resulted in sustained high response rates in patients with irritable bowel syndrome (IBS) and resulted in only mild side effects after 3 years, new data show.

Nearly three out of four people in a clinical trial experienced fewer symptoms and fatigue and a greater quality of life at both 2 years and 3 years after FMT in Norway. Those FMT-treated patients who relapsed subsequently responded to FMT upon retransplantation, reported the authors, who also correlated individual microbial profiles with clinical outcomes.

The study, led by Magdy El-Salhy, MD, PhD, department of medicine, Stord (Norway) Hospital, was published online in Gastroenterology.

An expert not involved with the study, Brian Lacy, MD, PhD, a gastroenterologist with the Mayo Clinic in Jacksonville, Fla., said that the results of the study are important, but he cautions against treating IBS with FMT outside clinical trials, at least until the protocol is validated, given demonstrated risks.

The new study included 125 patients (104 women, 21 men) in three groups: 38 received a placebo, 42 received 30 g of donor feces, and 45 received 60 g of donor feces. The feces – all from one male donor – was administered to the duodenum.

The response rates for those who received FMT were significantly higher than for those who received placebo. Those receiving 30 g of feces had a response rate of 69.1%, and those in the 60-g group had a response rate of 77.8%, whereas the response rate in the placebo group was 26.3%.

Patients provided a fecal sample and completed five questionnaires at the beginning of the study and at 2 and 3 years after FMT.

Patients in both treatment groups had significantly fewer IBS symptoms – such as abdominal pain, abdominal bloating, dissatisfaction with bowel habits, and quality-of-life interruption – and less fatigue compared with the placebo group, as well as higher quality of life scores at 2 and 3 years.

No long-term adverse effects were reported.

The dysbiosis index decreased only in the treatment group at years 2 and 3.
 

Microbial modifications correlate with IBS symptoms

In addition, the fluorescent signals of 10 bacteria that had changed after FMT were significantly correlated with improved IBS symptoms and fatigue in both treatment groups.

“Of the bacteria markers whose fluorescence signals changed in the 30-g and 60-g groups, but not in the placebo group, at both 2 and 3 years after FMT, nine were significantly correlated with the total IBS-SSS [IBS–Severity Scoring System] scores,” the authors wrote. One more bacterium with a changed fluorescence signal in the active treatment group also correlated with total fatigue.

Dr. El-Salhy told this news organization that those findings open the door for the select bacteria to be used, for example, in capsule form to treat IBS and fatigue.

The most surprising finding for the team was that the “majority of IBS patients [who] responded to FMT maintained response up to 3 years” or more, said Dr. El-Salhy, alluding to unpublished data up to 5 years.

“Furthermore, 80% of those who relapsed after 3 years responded to a new FMT,” he said.

Women had higher response rates than men at years 2 and 3 after FMT, but there were no differences between complete remission rates of women and men at years 2 and 3.
 

‘Impressive’ results, but caution warranted

“The results are impressive,” Dr. Lacy said. “I believe that this will help researchers around the world refine their techniques, as we learn more about FMT for the treatment of IBS. It also clearly plays up the importance of the gut microbiome in symptom generation in IBS patients.”

However, he said, until the results are replicated, and the protocol validated, FMT should not be used routinely to treat IBS because there are risks with the procedure.

Dr. Lacy pointed out there have been mixed results in the literature regarding FMT and IBS.

He cited a meta-analysis of four studies (n = 254) in 2019 that did not show a benefit for FMT in patients with IBS. However, a second meta-analysis of five studies (n = 267) did show some benefit, possibly owing to the type of donor and small-bowel infusion.

The authors added that, in the seven randomized, controlled trials investigating FMT for IBS, four concluded that FMT eased symptoms and improved quality of life in patients with IBS, whereas treatment was not effective in the other three.

The authors pointed to differences in protocols, donors, the cohort treated, FMT dose, and route of administration.

The longest response time previously studied in the randomized, controlled trials was 1 year, the authors pointed out. The new study was a 3-year follow-up of these authors’ previous randomly assigned placebo-controlled trial participants.
 

The ‘super-donor’ concept

The authors of the current study described the single chosen donor as “a healthy male aged 36 years with a normal BMI [body mass index] who was born via vaginal delivery, breastfed, a nonsmoker, was not taking any medication, was treated only a few times with antibiotics, exercised regularly, and consumed a sport-specific diet that was richer in protein, fiber, minerals, and vitamins than the average diet.”

The donor had high microbial diversity, and his fecal bacteria makeup was different from that of 254 healthy subjects for 14 of the 48 bacterial markers investigators tested.

Dr. Lacy said that the “super-donor” concept is noteworthy and an apparent key to success.

“Other studies have not done this,” Dr. Lacy noted.

Among the strengths of the study are that it included a relatively large cohort of patients with IBS, with three IBS subtypes and a single well-defined donor. However, it did not include the fourth IBS subtype, unsubtyped IBS, and it only investigated a part of the intestinal bacterial content, the authors acknowledged.

Most interesting, Dr. Lacy said, is that the IBS subtype did not seem to matter to FMT outcomes at 3 years and that all three subtypes responded better than placebo.

“That’s encouraging,” Dr. Lacy said.

The investigators received a grant from Helse Fonna. The study authors and Dr. Lacy reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Fecal microbiota transplantation (FMT) resulted in sustained high response rates in patients with irritable bowel syndrome (IBS) and resulted in only mild side effects after 3 years, new data show.

Nearly three out of four people in a clinical trial experienced fewer symptoms and fatigue and a greater quality of life at both 2 years and 3 years after FMT in Norway. Those FMT-treated patients who relapsed subsequently responded to FMT upon retransplantation, reported the authors, who also correlated individual microbial profiles with clinical outcomes.

The study, led by Magdy El-Salhy, MD, PhD, department of medicine, Stord (Norway) Hospital, was published online in Gastroenterology.

An expert not involved with the study, Brian Lacy, MD, PhD, a gastroenterologist with the Mayo Clinic in Jacksonville, Fla., said that the results of the study are important, but he cautions against treating IBS with FMT outside clinical trials, at least until the protocol is validated, given demonstrated risks.

The new study included 125 patients (104 women, 21 men) in three groups: 38 received a placebo, 42 received 30 g of donor feces, and 45 received 60 g of donor feces. The feces – all from one male donor – was administered to the duodenum.

The response rates for those who received FMT were significantly higher than for those who received placebo. Those receiving 30 g of feces had a response rate of 69.1%, and those in the 60-g group had a response rate of 77.8%, whereas the response rate in the placebo group was 26.3%.

Patients provided a fecal sample and completed five questionnaires at the beginning of the study and at 2 and 3 years after FMT.

Patients in both treatment groups had significantly fewer IBS symptoms – such as abdominal pain, abdominal bloating, dissatisfaction with bowel habits, and quality-of-life interruption – and less fatigue compared with the placebo group, as well as higher quality of life scores at 2 and 3 years.

No long-term adverse effects were reported.

The dysbiosis index decreased only in the treatment group at years 2 and 3.
 

Microbial modifications correlate with IBS symptoms

In addition, the fluorescent signals of 10 bacteria that had changed after FMT were significantly correlated with improved IBS symptoms and fatigue in both treatment groups.

“Of the bacteria markers whose fluorescence signals changed in the 30-g and 60-g groups, but not in the placebo group, at both 2 and 3 years after FMT, nine were significantly correlated with the total IBS-SSS [IBS–Severity Scoring System] scores,” the authors wrote. One more bacterium with a changed fluorescence signal in the active treatment group also correlated with total fatigue.

Dr. El-Salhy told this news organization that those findings open the door for the select bacteria to be used, for example, in capsule form to treat IBS and fatigue.

The most surprising finding for the team was that the “majority of IBS patients [who] responded to FMT maintained response up to 3 years” or more, said Dr. El-Salhy, alluding to unpublished data up to 5 years.

“Furthermore, 80% of those who relapsed after 3 years responded to a new FMT,” he said.

Women had higher response rates than men at years 2 and 3 after FMT, but there were no differences between complete remission rates of women and men at years 2 and 3.
 

‘Impressive’ results, but caution warranted

“The results are impressive,” Dr. Lacy said. “I believe that this will help researchers around the world refine their techniques, as we learn more about FMT for the treatment of IBS. It also clearly plays up the importance of the gut microbiome in symptom generation in IBS patients.”

However, he said, until the results are replicated, and the protocol validated, FMT should not be used routinely to treat IBS because there are risks with the procedure.

Dr. Lacy pointed out there have been mixed results in the literature regarding FMT and IBS.

He cited a meta-analysis of four studies (n = 254) in 2019 that did not show a benefit for FMT in patients with IBS. However, a second meta-analysis of five studies (n = 267) did show some benefit, possibly owing to the type of donor and small-bowel infusion.

The authors added that, in the seven randomized, controlled trials investigating FMT for IBS, four concluded that FMT eased symptoms and improved quality of life in patients with IBS, whereas treatment was not effective in the other three.

The authors pointed to differences in protocols, donors, the cohort treated, FMT dose, and route of administration.

The longest response time previously studied in the randomized, controlled trials was 1 year, the authors pointed out. The new study was a 3-year follow-up of these authors’ previous randomly assigned placebo-controlled trial participants.
 

The ‘super-donor’ concept

The authors of the current study described the single chosen donor as “a healthy male aged 36 years with a normal BMI [body mass index] who was born via vaginal delivery, breastfed, a nonsmoker, was not taking any medication, was treated only a few times with antibiotics, exercised regularly, and consumed a sport-specific diet that was richer in protein, fiber, minerals, and vitamins than the average diet.”

The donor had high microbial diversity, and his fecal bacteria makeup was different from that of 254 healthy subjects for 14 of the 48 bacterial markers investigators tested.

Dr. Lacy said that the “super-donor” concept is noteworthy and an apparent key to success.

“Other studies have not done this,” Dr. Lacy noted.

Among the strengths of the study are that it included a relatively large cohort of patients with IBS, with three IBS subtypes and a single well-defined donor. However, it did not include the fourth IBS subtype, unsubtyped IBS, and it only investigated a part of the intestinal bacterial content, the authors acknowledged.

Most interesting, Dr. Lacy said, is that the IBS subtype did not seem to matter to FMT outcomes at 3 years and that all three subtypes responded better than placebo.

“That’s encouraging,” Dr. Lacy said.

The investigators received a grant from Helse Fonna. The study authors and Dr. Lacy reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Zelnorm (tegaserod), an oral short-term treatment of irritable bowel syndrome and constipation (IBS-C), is being removed from the U.S. market effective June 30, according to the manufacturer, Alfasigma.

The Italian pharmaceutical company said the drug is being removed for business purposes, not because of any concern involving its safety or efficacy, nor has it been recalled.

The drug has been through a teeter totter of regulations since its inception.

When it was first introduced in 2002, Zelnorm was a first-of-its-kind drug and was intended to treat all women with IBS-C in the short term. But it was removed from the market 5 years later following concerns about cardiovascular side effects. Clinical data showed an increased incidence of stroke and angina in women taking Zelnorm.

Despite these concerns, the U.S. Food and Drug Administration voted to reintroduce the drug into the market in 2019, but only for women without a history of heart health problems.

Though Alfasigma will stop making the drug, a company news release said current users can continue use for a while.

“Patients will continue to have access to Zelnorm (tegaserod) for as long as the existing supply of product remains in the trade channel,” Alfasigma said in a news release about the drug removal. The company urged its customers to discuss alternative IBS medications with their doctor.

Zelnorm is a serotonin agonist, meaning it binds to receptors and stops the release of serotonin into the system. These sorts of drugs can decrease the pain associated with IBS and help increase gut motility in order to pass stool. Other drugs besides Zelnorm that use this mechanism include alosetron and cilansetron.

A version of this article first appeared on Medscape.com.

Zelnorm (tegaserod), an oral short-term treatment of irritable bowel syndrome and constipation (IBS-C), is being removed from the U.S. market effective June 30, according to the manufacturer, Alfasigma.

The Italian pharmaceutical company said the drug is being removed for business purposes, not because of any concern involving its safety or efficacy, nor has it been recalled.

The drug has been through a teeter totter of regulations since its inception.

When it was first introduced in 2002, Zelnorm was a first-of-its-kind drug and was intended to treat all women with IBS-C in the short term. But it was removed from the market 5 years later following concerns about cardiovascular side effects. Clinical data showed an increased incidence of stroke and angina in women taking Zelnorm.

Despite these concerns, the U.S. Food and Drug Administration voted to reintroduce the drug into the market in 2019, but only for women without a history of heart health problems.

Though Alfasigma will stop making the drug, a company news release said current users can continue use for a while.

“Patients will continue to have access to Zelnorm (tegaserod) for as long as the existing supply of product remains in the trade channel,” Alfasigma said in a news release about the drug removal. The company urged its customers to discuss alternative IBS medications with their doctor.

Zelnorm is a serotonin agonist, meaning it binds to receptors and stops the release of serotonin into the system. These sorts of drugs can decrease the pain associated with IBS and help increase gut motility in order to pass stool. Other drugs besides Zelnorm that use this mechanism include alosetron and cilansetron.

A version of this article first appeared on Medscape.com.

Zelnorm (tegaserod), an oral short-term treatment of irritable bowel syndrome and constipation (IBS-C), is being removed from the U.S. market effective June 30, according to the manufacturer, Alfasigma.

The Italian pharmaceutical company said the drug is being removed for business purposes, not because of any concern involving its safety or efficacy, nor has it been recalled.

The drug has been through a teeter totter of regulations since its inception.

When it was first introduced in 2002, Zelnorm was a first-of-its-kind drug and was intended to treat all women with IBS-C in the short term. But it was removed from the market 5 years later following concerns about cardiovascular side effects. Clinical data showed an increased incidence of stroke and angina in women taking Zelnorm.

Despite these concerns, the U.S. Food and Drug Administration voted to reintroduce the drug into the market in 2019, but only for women without a history of heart health problems.

Though Alfasigma will stop making the drug, a company news release said current users can continue use for a while.

“Patients will continue to have access to Zelnorm (tegaserod) for as long as the existing supply of product remains in the trade channel,” Alfasigma said in a news release about the drug removal. The company urged its customers to discuss alternative IBS medications with their doctor.

Zelnorm is a serotonin agonist, meaning it binds to receptors and stops the release of serotonin into the system. These sorts of drugs can decrease the pain associated with IBS and help increase gut motility in order to pass stool. Other drugs besides Zelnorm that use this mechanism include alosetron and cilansetron.

A version of this article first appeared on Medscape.com.

 The study by D'Amico and colleagues underscores the importance of using biologic therapies early in the postoperative course to prevent endoscopic recurrence. Patients who require surgery should initiate biologic therapy as soon as they have completed postoperative healing. This will help prevent a recurrence of their Crohn's disease and limit the need for subsequent surgery in the future. Proactive monitoring for postoperative recurrence and prompt management of any inflammation identified is vital in improving long-term outcomes.

 Meanwhile, Rosiou and colleagues highlight the importance of communication with the entire care team regarding the management of IBD flares. Proactive patient education about notifying the primary gastroenterology provider if they experience flare symptoms can help prevent inappropriate or excess steroid exposure. Steroid-sparing strategies for the induction and maintenance of IBD remission are pivotal in preventing side effects and long-term complications of steroid exposure. Steroids should be used as a short-term therapy while bridging to a safe and appropriate maintenance regimen.

 The study by D'Amico and colleagues underscores the importance of using biologic therapies early in the postoperative course to prevent endoscopic recurrence. Patients who require surgery should initiate biologic therapy as soon as they have completed postoperative healing. This will help prevent a recurrence of their Crohn's disease and limit the need for subsequent surgery in the future. Proactive monitoring for postoperative recurrence and prompt management of any inflammation identified is vital in improving long-term outcomes.

 Meanwhile, Rosiou and colleagues highlight the importance of communication with the entire care team regarding the management of IBD flares. Proactive patient education about notifying the primary gastroenterology provider if they experience flare symptoms can help prevent inappropriate or excess steroid exposure. Steroid-sparing strategies for the induction and maintenance of IBD remission are pivotal in preventing side effects and long-term complications of steroid exposure. Steroids should be used as a short-term therapy while bridging to a safe and appropriate maintenance regimen.

 The study by D'Amico and colleagues underscores the importance of using biologic therapies early in the postoperative course to prevent endoscopic recurrence. Patients who require surgery should initiate biologic therapy as soon as they have completed postoperative healing. This will help prevent a recurrence of their Crohn's disease and limit the need for subsequent surgery in the future. Proactive monitoring for postoperative recurrence and prompt management of any inflammation identified is vital in improving long-term outcomes.

 Meanwhile, Rosiou and colleagues highlight the importance of communication with the entire care team regarding the management of IBD flares. Proactive patient education about notifying the primary gastroenterology provider if they experience flare symptoms can help prevent inappropriate or excess steroid exposure. Steroid-sparing strategies for the induction and maintenance of IBD remission are pivotal in preventing side effects and long-term complications of steroid exposure. Steroids should be used as a short-term therapy while bridging to a safe and appropriate maintenance regimen.