Anti-Inflammatory Biologics and Anti-Tumoral Immune Therapies-Associated Colitis: A Focused Review of Literature

Abstract

An increasing number of drugs including monoclonal antibodies and small molecules, either anti-inflammatory or immunity-enhancing, have been developed to treat human diseases and the number of medications in these classes is likely to expand in the future. The two most commonly used categories of such therapies are the anti-inflammatory group (anti- tumor necrosis factor (TNF) α, anti-interleukins/interleukin receptors, and anti-integrin bodies) and the anti-tumoral agents (immune checkpoint inhibitors, anti-CD20, and anti-endothelial growth factor). Although the anti-inflammatory biologics have brought about a revolutionary effect in the management of a variety of autoimmune disorders including rheumatologic diseases, inflammatory bowel disease, and inflammatory dermatological diseases, their ability to induce colitis in patients without a prior history of colitis or exacerbate quiescent colitis has been increasingly and unexpectedly recognized. While the use of immune-augmenting monoclonal antibody therapies results in a significant survival benefit in a subset of patients with malignancies, these monoclonal antibodies also have the ability to cause colitis through an apparent autoimmune mechanism. Colitis associated with these medications may demonstrate multiple histologic patterns including increased apoptosis (graft versus host disease (GVHD)-like), autoimmune enteropathy pattern, acute colitis pattern, ischemic colitis, inflammatory bowel disease pattern, either ulcerative colitis-like, Crohn’s disease-like, or fulminant colitis-like. In addition, anti-inflammatory biologics are known to cause or reactivate latent infections such as tuberculosis and increase the risk for malignancies including high-grade lymphomas as well as indolent lymphoproliferative disorders. Thus, the differential diagnosis for colitis in patients receiving therapeutic anti-inflammatory biologics or anti-tumoral agents can be broad. Optimal diagnosis and treatment requires a multidisciplinary approach. This review aims to provide an overview of the literature on the clinical features, histology, and treatment of these newly recognized anti-inflammatory biologic and anti-tumoral immune therapy-induced colitises and hopes this outlines will raise the vigilance of all clinicians of these entities.

Healthcare resource utilization and costs associated with inflammatory bowel disease among patients with chronic inflammatory diseases: a retrospective cohort study

“…Similarly, a large realworld retrospective longitudinal cohort study of the incidence of IBD among patients with CIDs treated with IL-17 blockers or PDE4 inhibitors found that treatment with IL-17 antagonists was associated with more than 3fold higher odds of having IBD relative to patients naïve to biologics and patients treated with biologics not indicated for the treatment of IBD [38]. Finally, a number of studies also found that etanercept was associated with exacerbation of existing IBD or new onset IBD [21,22].…”

“…However, there is evidence suggesting that some of these treatments may increase the risk of developing new onset IBD or exacerbating existing IBD in patients with CIDs [12,14,15]. The use of certain biologic therapies such as etanercept (a tumor necrosis factor inhibitor) and interleukin-17 antagonists in patients with CIDs is cautioned due to possible increased risk of IBD [16][17][18][19][20][21][22].…”

Granulomatous colitis in a patient with metastatic melanoma under immunotherapy: a case report and literature review

“…Another histological pattern is "lymphocytic colitis" similar to the one observed in ipilimumab-related injury, while recurrent anti-PD1 colitis can result in IBDlike chronic active colitis [23,25]. Few cases of ICPIsinduced collagenous colitis have also been reported [26][27][28]. Concerning lymphocytic subsets, T cell population prevails in ICPIs-associated colitis.…”

Severe erosive gingivostomatitis in a patient treated by vedolizumab

“…Vedolizumab is a humanized monoclonal antibody that binds to the human α4β7 integrin, approved for use in inflammatory bowel diseases (IBD), [1]. Our patient presented with refractory erosive gingivostomatitis, a few days after the initial dose of vedolizumab.…”