Current Treatments for Patients With Inflammatory Bowel Diseases Experiencing Extraintestinal Manifestations

Researchers summarized the current knowledge on treatment options for extraintestinal manifestations in patients with IBD, while calling attention to gaps in the research.

Randomized clinical trials are still needed to expand treatment options for extraintestinal manifestations (EIMs) among patients with inflammatory bowel diseases (IBDs). These perspectives were stated in a review of recent advances in IBD treatments published in Gut.

EIMs most commonly involve joints, skin, eyes, liver, and/or the biliary tract and are reported by as many as 47% of patients with IBDs. The frequency of EIMs increases with disease duration and the presence of an EIM predisposes patients to develop additional EIMs. These conditions should be targeted for therapy, as their presence has been associated with increased morbidity and mortality.

Anti-tumor necrosis factor (TNF), biologics, and small molecule therapies have dramatically altered the treatment landscape for patients with EIMs. However, there has been little available data on the treatment efficacy of these newer therapies.

The conventional treatments for EIMs have included short-term, non-steroidal anti-inflammatory drugs (NSAIDs), steroids, sulfasalazine methotrexate, and calcineurin inhibitors.

There are 2 opposing hypotheses justifying the development of therapeutic options for the treatment of EIMs: 1) these conditions are an extension of the immune response in the gut, or 2) they are an independent inflammatory event. Although there are a lack of specific animal models in which to test these hypotheses, newer single-cell technologies may allow for more precise studies of the specific inflammatory mechanisms of EIMs.

Anti-TNF has been recommended for the treatment of uveitis episcleritis, resistant peripheral arthritis cases, early use among patients with axial spondyloarthropathy or pyoderma gangrenosum, and for severe or refractory erythema nodosum.

Anti-integrins have been found to successfully treat up to 50% of patients with peripheral arthritis and patients with erythema nodosum who do not have mucosal vascular addressin cell adhesion molecule 1 (MAdCAM1) skin expression.

Janus kinase (JAK) inhibitors and anti-interleukin (IL)-12/23 have been approved for the treatment of other arthritis and psoriasis disease states, which may indicate they could also be effective for the treatment of EIMs involving joints or skin. JAK inhibitors were efficacious in a trial of patients with axial spondyloarthropathy, though they have not yet been approved for this use. Additionally, JAK inhibitors successfully treated 2 patients with uveitis episcleritis. IL-12/23 was successful in the treatment of a single patient with uveitis episcleritis.

In recent years the development of these new pharmaceuticals has given patients with EIMs more treatment options. However, randomized controlled trials are needed in order to address pressing questions, such as: Are combinatorial therapies effective for EIM treatment? At what point in the disease course should patients with IBD and EIMs be given biologics?

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Greuter T, Rieder F, Kucharzik T, et al. Emerging treatment options for extraintestinal manifestations in IBD. Gut. 2021;70(4):796-802. doi: 10.1136/gutjnl-2020-322129