Female sex, genetics, smoking status linked to extraintestinal manifestation in IBD

Key takeaways:

• Extraintestinal manifestations were more common in women (OR = 1.2), Crohn’s (OR = 1.7) and among those who required surgery (OR = 1.7).
• Smoking had a “protective” effect in primary sclerosing cholangitis.

Female sex, smoking, Crohn’s disease and a history of surgery to treat inflammatory bowel disease were associated with an increased risk for developing extraintestinal manifestations of disease, according to research in Gastroenterology.

“Extraintestinal manifestations in IBD patients can impact their quality of life and contribute significantly to morbidity,” Talin Haritunians, PhD, senior study author and research associate professor of medicine at Cedars-Sinai, told Healio. “Our goal was to better understand which IBD patients are at increased risk for extraintestinal manifestations and understand what the underlying causes of these manifestations are.”

In the “largest multicenter study to date,” Haritunians and colleagues investigated clinical, serological and genetic factors associated with extraintestinal manifestation complications in patients with IBD. They reviewed data from 12,083 cases from Cedars-Sinai Medical Center IBD Research Repository, SHARE and NIDDK IBD Genetics consortiums and the RISK cohort.

Researchers identified several extraintestinal manifestation phenotypes in the dataset, including peripheral arthritis (17%), skin manifestations (6.5%), primary sclerosing cholangitis (3.8%), ankylosing spondylitis and sacroiliitis (3.3%), psoriasis (3%), erythema nodosum (2.6%), ocular manifestations (2.4%) and pyoderma gangrenosum (1.2%).

Most manifestations were observed among patients with Crohn’s disease vs. ulcerative colitis (OR = 1.7; 95% CI, 1.4-2), as well as in women (OR = 1.2; 95% CI, 1.1-1.4) and among those who required surgery for IBD (OR = 1.7; 95% CI, 1.5-1.9). Smoking increased the risk for several manifestations, with the exception of primary sclerosing cholangitis, for which it was “protective,” researchers noted.

“We observed that female sex, smoking status, IBD subtype, location of the inflammation, a history of surgery to treat IBD, antibody responses to commensal flora and genetic variation are important factors in the development of extraintestinal complications in IBD,” Haritunians said.

Researchers also reported genome-wide genetic associations within the major histocompatibility complex, including ankylosing spondylitis and sacroiliitis (OR = 2.5; 95% CI, 2-3.1), primary sclerosing cholangitis (OR = 2.8; 95% CI, 2-3.8), ocular manifestations (OR = 3.6; 95% CI, 2.3-5.6) and overall extraintestinal manifestations (OR = 2.2; 95% CI, 1.7-2.9), as well associations for the known IBD locus CPEB4 and skin manifestations (OR = 1.5; 95% CI, 1.3-1.8).

These findings suggest that tumor necrosis factor, the Janus kinase signal transducer and activator of transcription pathway and interleukin 6 may be “potential targets” for treating extraintestinal manifestations.

“Up to 40% of people with IBD suffer from inflammatory manifestations outside the gut, including the liver, skin and joints,” Dermot P.B. McGovern, MD, PhD, study author and director of translational research at the Cedars-Sinai F. Widjaja Inflammatory Bowel Disease Institute, told Healio. “Our findings will help identify patients at increased risk of developing these manifestations.”

He continued: “Understanding the underlying mechanisms of these complications gets us closer to developing novel therapeutic options to improve patient care and may inform treatment choices with our existing therapies.”

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Sources/Disclosures

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Disclosures:
Haritunians reports no relevant financial disclosures. McGovern reports consulting for Bridge Biotherapeutics, Merck, Palatin Technologies and Takeda. Please see the study for all other authors’ relevant financial disclosures.

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