BIOLOGICS AND SMALL MOLECULES USED IN IBD MIMICS: HIGHLIGHTING THE IMPORTANCE OF DIAGNOSIS CONFIRMATION
Authors: Fiske Hannah , Ward Christopher , Shah Samir , Clarke Kofi , Williams Emmanuelle , Farraye Francis , Siegel Corey , Cross Raymond , Hull Tracy , Binion David , Wexner Steven , Goyal Alka , Lazarev Mark , Dueker Jeffrey , Hanson John , Watson Andrew , Al-Bawardy Badr , Barnes Edward , Brand Myron , Melia Joanna , Ginsburg Philip , Herfath Hans , Forster Erin , Engels Mike , Qazi Taha , Bohm Matthew , Cohen Benjamin , Dam Aamir , Fine Sean , Gaidos Jill , Holubar Stefan , Levy L Campbell , Philpott Jessica , Rubin Jonah , Regueiro Miguel 
Published: January 2024

Abstract

INTRODUCTION
Since 2009, inflammatory bowel disease (IBD) specialists have been utilizing “IBD Live,” a weekly live video conference with a global audience of 150-200 participants, to discuss the multidisciplinary management of their commonly seen and most challenging cases. While most cases presented were confirmed as IBD, a substantial number were mimics for which IBD was not the ultimate diagnosis. We previously categorized all IBD Live cases and identified the frequency of “IBD mimics.” Here, we examine the use of biologic medications for these cases which ultimately were determined to be something other than IBD.

METHODS
Cases have been recorded and archived since May 2018. 371 total cases from May 2018 through February 2023 were reviewed spanning 186 hours. 65 of those cases were determined to be IBD mimics, defined as those with features of IBD that ultimately resulted in a non-IBD diagnosis. IBD mimics were analysed and categorized in terms of their biologic usage.

RESULTS
25 of the 65 mimics (38.5%) were treated with biologics for presumed IBD. 14 were treated with one biologic, 5 with two biologics, and 6 with three or more biologics.
The biologics used in the management of these IBD mimics included infliximab (n=21), vedolizumab (n=12), adalimumab (n=11), ustekinumab (n=6), and certolizumab (n=1).
Of the 25 cases of biologic usage without definitive confirmation of IBD, 6 ended up with a diagnosis where biologics were an appropriate treatment for the mimic. These mimics included drug-induced colitis (n=3), Behcet’s disease (n=1), segmental colitis associated with diverticulosis (SCAD; n=1), and CTLA-4 haploinsufficiency with autoimmune infiltrates (CHAI; n=1).
Several of the IBD mimics were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialled on tofacitinib (for Sweet’s syndrome, PIK3cd, and SCAD).
There were 3 patients with confirmed IBD, in remission on a biologic, who subsequently had symptoms concerning for an IBD flare. In each of these cases, IBD was not the cause of their symptoms (e.g., cecal volvulus).
There were 4 patients with confirmed IBD, in remission off biologics, who later developed symptoms suspicious for an IBD flare. Each of these cases was trialled on biologics to treat the supposed flare; however, symptoms were ultimately found to be due to an IBD mimic (e.g., eosinophilic esophagitis).
33 of the 65 IBD mimics were never treated with biologics.

DISCUSSION
In a 5-year period at IBD Live, 17.5% of cases (65 of 371) were found to be IBD mimics. 38.5% (25 of 65) of these were treated with biologics. The diverse presentation of signs and symptoms of IBD and IBD mimics requires reassessment of the biologic therapy in patients without response. Often the biologic needs to be optimized for IBD, but in some cases, the diagnosis of IBD will need to be called into question.

Table 1 IBD mimics and biologics used

Abbreviations
BADAS = bowel-associated dermatosis-arthritis syndrome, BCL = B-cell lymphoma, CD = Crohn’s Disease, CHAI = CTLA-4 haploinsufficiency with autoimmune infiltrates, C-MUSE = cryptogenic multifocal ulcerous stenosing enteritis, CMV = cytomegalovirus, CVID = common variable immunodeficiency, EGPA = eosinophilic granulomatosis with polyangiitis, GABA = gamma-aminobutyric acid, IBD = inflammatory bowel disease, IMHMV = idiopathic myointimal hyperplasia of the mesenteric veins, PIK3cd = phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit delta, PNH = paroxysmal nocturnal hemoglobinuria, SCAD = segmental colitis associated with diverticulosis, STI = sexually transmitted infection, UC = Ulcerative Colitis.

Image 1: Biologic usage in IBD mimics