Mo1203 Clinical Risk Factors for Complications After Laparoscopic Ileal-Pouch-Anal Anastomosis in Patients With Ulcerative Colitis

Abstract

Background: The advent of biologic agents that bind to tumor necrosis factor (TNF) has revolutionized therapy of inflammatory bowel disease (IBD). However, these agents carry a unique set of adverse effects, including development of a lupus-like syndrome termed antiTNF induced lupus (ATIL). This adverse effect often leads to cessation of the anti-TNF agent. The clinical manifestations and criteria for ATIL are incompletely defined in patients with IBD. We explored aspects of ATIL in a series of IBD patients. Methods: Patients from the University of Calgary IBD clinic in whom ATIL was diagnosed by the treating physician were included (N=10). Ethics approval was obtained from the Conjoint Health Research Ethics Board at the University of Calgary. Charts were reviewed for pertinent clinical data. Blood was drawn and sent for serology including anti-nuclear antibody (ANA) and extractable nuclear antigens (ENA), by the Mitogen Advanced Diagnostics Laboratory (mitogen.ca, Calgary, AB). DNA was sent to the Sanger Institute (Cambridge, UK) for whole-exome sequencing (analysis pending). Results: The cohort consisted of largely females (8/10) with Crohn's disease (CD) (7/10). In CD patients, disease location was mainly ileocolonic (6/7), while all UC patients had left-sided disease (3/3). Median age at diagnosis was 39 (range 19-62). Seven patients developed ATIL on infliximab, and 3 on adalibumab. Reported manifestations included rash (70%), and arthritis (50%) or arthralgias (40%). Antinuclear antibody (ANA) was positive in 9 patients. The most common pattern was speckled (7/9) and homogenous (5/9), with a median titer of 1:320. No patients were ENA positive. All patients had thiopurine exposure, and 50% had a previous adverse reaction to thiopurines (2 hepatotoxicity, 2 leukopenia, and 1 pancreatitis). Of patients who developed ATIL on adalibumab, 2/3 had a history of infusion reaction to infliximab. Six patients who developed ATIL on infliximab subsequently received adalibumab, 3/6 developing recurrent ATIL symptoms. Conclusions: In the present study we sought to characterize ATIL in a series of IBD patients. There was a predominance of ileocolonic CD patients treated with infliximab; this may purely reflect historical predominance of infliximab use. However, a putative mechanism of ATIL is via anti-cellular immunity against cells expressing membrane-bound anti-TNF, and it is possible that the chimeric infliximab induces more avid epitope spreading, and thus predisposes to ATIL. There was a high prevalence of previous adverse reaction to thiopurines, suggesting a possible association with development of ATIL. Introduction of another anti-TNF agent was possible in some without recurrent ATIL. Understanding characteristics of ATIL may help in early recognition and development of predictive markers of this important adverse effect.