P403 The role of Organic Cation Transporter (OCTN)-1 in predicting individual response to therapy in Ulcerative Colitis: towards a personalized approach

Abstract

Abstract Background Ulcerative colitis is a chronic invalidating disease, whose therapeutic strategies include amino-salicylates, steroids, probiotics, immune-modulators, biologics, fecal microbiota transplantation and surgery. In clinical practice, there is little evidence available about elements that could predict response to each of the above-mentioned therapies. Our study suggests that OCTN1, an organic cation transporter directly involved in innate immunity, with its variants (C503L homozygous, heterozygous or T503F), could have a role in predicting individual response to biologic therapies (antiTNFa and vedolizumab). Methods In this prospective study, we enrolled a cohort of, 80 patients with active ulcerative colitis (51 in treatment with anti-TNF alpha agents and, 29 with vedolizumab), determining their OCTN1 genotype and evaluating their clinical response to therapy, calculated with clinical Mayo score, after six weeks (T1), six months (T2) and after three years (T3). Results Left colitis at diagnosis was more frequent in C503L patients (60% left colitis vs, 40% pancolitis) than patients with T503F (42.8% left colitis vs, 57.2 pancolitis). In the same way, the average age at diagnosis was sensibly lower in patients with T503F genotype (34.7 years C503L vs, 25 years T503F). We used clinical response at T2 (6 months) as a primary outcome of our study. Among patients under anti-TNF alpha therapies, patients with C503L genotype were divided into, 8 no responders and, 6 responders (43% responders vs, 57% no responders); patients with T503F genotype were divided into, 10 responders and, 2 no responder (80% responders vs, 20% no responders). On the contrary, patients under vedolizumab therapy showed different trends: patients with C503L genotype were divided into, 12 responders and, 3 no responders (83% responders vs, 17% no responders); patients with T503F genotype were, 1 responder and, 1 no responder (50% responders vs, 50% no responders). After, 3 years, patients responders to anti-TNF alpha therapies at T2, with T503F genotype, still maintain the response to the same drug. Conclusion Patients with the T503F genotype present an overall worse course of the disease, with a higher rate of pancolitis and younger age at diagnosis. Patients with the C503L genotype showed a better response to vedolizumab, whilst patients with the T503F genotype showed a better response to anti-TNF alpha. We can therefore conclude that the presence of the mutation (allele T) increases the response rate to anti-TNF alpha, especially for the homozygous mutated genotype (OR=371.82, p=0.009), but for the heterozygous genotype as well (OR=10.95, p=0.088).