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Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center
Dr. Dermot McGovern

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

 

 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

Dr. David T. Rubin


“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”

In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.

“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”

The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.

A version of this article appeared on Medscape.com.

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Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center
Dr. Dermot McGovern

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

 

 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

Dr. David T. Rubin


“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”

In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.

“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”

The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center
Dr. Dermot McGovern

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

 

 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

Dr. David T. Rubin


“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”

In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.

“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”

The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.

A version of this article appeared on Medscape.com.

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