P0673Higher serum IL-23 levels associated with development of dermatological complications of anti-TNF therapy in Crohn’s Disease

Background Observational data has reported anti-TNF related dermatological complications in patients with IBD at 20-22%1,2. Previous histological assessment of some of these lesions have identified skin infiltrates rich in IL-12, IL-17 and IL-233. Underlying aetiology is currently unclear. We aimed to characterise the clinical and inflammatory cytokine profile of patients with IBD who develop dermatological complications of anti-TNF treatment. Methods Patients who were receiving anti-TNF therapy and developed dermatological complications were prospectively recruited from IBD outpatient clinics in a tertiary referral centre. Age and disease matched controls were identified. All patients were reviewed by dermatology to confirm diagnosis. Serum samples and disease phenotype were collected at time of recruitment. Serum cytokine concentrations were quantified using cytometric bead array (IL-8, IL-1, IL-6, IL-10, TNF, IL-12p70)(BD Biosciences) and enzyme linked immunosorbent assays (IL-17 and IL-23) (DuoSet R&D Systems). Results Thirty-three patients were recruited. 51.5% (n = 17) were diagnosed as having a dermatological complication of anti-TNF therapy. The majority developed psoriasiform dermatitis (47%). The mean time to diagnosis was 18 months (IQR 2- 48). Seventeen (55%) patients had CD. Twenty-five (76%) patients had serum samples for cytokine analysis. Pancolitis (n = 8; 72.7%) and small bowel disease (n = 3; 50%) were the most frequent distribution of disease in patients who developed dermatological complications with UC and CD respectively. A trend toward lower mean concentrations of TNF and higher mean concentrations of IL-8, IL-17 & IL-23 was noted in those who developed cutaneous complication compared to controls. However, in those who developed skin complications, patients with CD had significantly higher IL-23 serum levels in comparison to those patients with UC (Mann-Whitney p = 0.026). Although not statistically significant, patients who developed dermatological complications had higher mean anti-TNF trough levels (15.1mcg/ml vs.6.6mcg/ml p = 0.051). No statistical correlation between anti-TNF antibodies or disease response and development of skin complications was identified. Conclusion Patients with CD who develop skin complications secondary to anti-TNF therapy have higher serum levels of IL-23. Lower serum TNF and higher serum IL-17 and IL-23 concentrations is consistent with previous hypothesis related to paradoxical psoriasis4. However, our data suggests that this may be a mechanism more prominent in patients with CD. These findings support further investigation in larger, more representative samples. References: 1. Cleynen I, Vermeire S. Paradoxical inflammation induced by anti-TNF agents in patients with IBD. Nat Rev Gastroenterol Hepatol. Sep 2012;9(9):496-503. doi:10.1038/nrgastro.2012.125 2. Freling E, Baumann C, Cuny JF, et al. Cumulative incidence of, risk factors for, and outcome of dermatological complications of anti-TNF therapy in inflammatory bowel disease: a 14-year experience. Am J Gastroenterol. Aug 2015;110(8):1186-96. doi:10.1038/ajg.2015.205 3. Tillack C, Ehmann LM, Friedrich M, et al. Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-gamma-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment. Gut. Apr 2014;63(4):567-77. doi:10.1136/gutjnl-2012-302853 4. Toussirot E, Aubin F. Paradoxical reactions under TNF-alpha blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview. RMD Open. 2016;2(2):e000239. doi:10.1136/rmdopen-2015-000239 Conflict of interest: Dr. Mchale, Ciarán: No conflict of interest Mc Gettigan, Neasa: No conflict of interest Beatty, Paula: No conflict of interest O’Sullivan, David: No conflict of interest McKenna-Barry, Matthew: No conflict of interest Schilling, Carole: No conflict of interest Dowling, Jennifer: No conflict of interest Roche, Muireann: No conflict of interest Boland, Karen: No conflict of interest