Biologics for Extraintestinal Manifestations of IBD

Abstract

Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) occur frequently and may present themselves before or after IBD diagnosis. They most commonly affect the eyes, skin, and joints, but can also involve other organs such as the liver. Some EIM are associated with intestinal disease activity and ameliorate by treatment of the underlying IBD. This is seen in patients with peripheral Type 1 arthritis, oral aphthous ulcers, episcleritis, and erythema nodosum. Other EIM are intestinal disease activity-independent such as uveitis, and ankylosing spondylitis. Finally, some EIM (e.g. pyoderma gangrenosum and primary sclerosing cholangitis) may or may not be associated with the underlying IBD. Successful therapy of EIM is important for improving quality of life of IBD patients. TNF antibody therapy is an important treatment option for EIM in IBD patients whereas no such beneficial effect was reported for alpha 4 beta 7 integrin antibodies such as vedolizumab so far. This article reviews the therapeutic experience with TNF antibodies for the treatment of EIM in IBD patients.

Cutaneous manifestations in inflammatory bowel disease: a single institutional study of non‐neoplastic biopsies over 13 years

“…This genetic overlap among ulcerative colitis and Crohn disease is not surprising, given the clinical similarities and the occurrence of diagnoses changing over time. Many of the implicated genes are receptors, ligands and other proteins with crucial roles at multiple steps in the innate inflammatory cascade, such as NOD2, ATG16L1 and IRGM in Crohn disease, or in the adaptive immune response, such as IL23R, and human leukocyte antigen locus (HLA), in ulcerative colitis; highlighting the role that innate immunity plays in shaping the adaptive immune response . Both alimentary and integumentary systems represent epithelial lined surfaces with their own immune microenvironment, whereby immune cells constantly interact with threatening and non‐threatening microbes in the external environment and choose when to attack and when to tolerate .…”

Systematic Review of Tumor Necrosis Factor Antagonists in Extraintestinal Manifestations in Inflammatory Bowel Disease

“…Several literature reviews have been published in the last few years trying to summarize the evidence available on the use of biologic drugs for the management of EIMs in IBD. [16][17][18] The authors of these studies concluded that anti-TNF therapy should be considered in patients with EIMs because of beneficial effect observed. However, none of these reviews have been conducted through a systematic approach.…”

The current state of the art for biological therapies and new small molecules in inflammatory bowel disease

“…1). This class of biologics, characterized by a relatively quick onset of action, is highly effective in both the gastrointestinal 9,10 and extra-intestinal 11 manifestations of disease, and remains the most widely used biologic class in the treatment of IBD. Initial concerns regarding the safety of these agents have decreased with accumulating data.…”

“…The anti-TNF agents also have the most evidence supporting their use in the treatment of the multitude of extra-intestinal manifestations (including articular, ocular, and dermatologic) of IBD. 11 While there have not been direct comparative trials between the various anti-TNF agents, infliximab with its intravenous route of administration, weight-based dosing, ease in flexibility of dosing, and speed of onset is often the preferred choice in severe disease and hospitalized patients. There is a concern that the subcutaneous anti-TNF agents (adalimumab, certolizumab pegol in CD, and golimumab in UC) that are not weight based may in fact be underdosed in a significant proportion of patients, especially in ulcerative colitis, and there are in fact trials currently underway reexamining the efficacy of higher-dose adalimumab therapy (SERENE UC—NCT02065622 and SERENE CD—NCT02065570).…”

“…83,84 Furthermore, though vedolizumab is approved for use in CD, the trial data are not as impressive as for UC, and as such it is less frequently considered a first-line therapy in this condition, especially small bowel CD. Also, while the gut specificity is promoted with respect to the safety of vedolizumab, this property theoretically limits its efficacy in the treatment of patients with significant extra-intestinal manifestations, 11 though a recent multicenter cohort study suggested vedolizumab may have some benefit with resolution of inflammatory arthritis in close to half of patients. 85 …”