P403 The role of Organic Cation Transporter (OCTN)-1 in predicting individual response to therapy in Ulcerative Colitis: towards a personalized approach.
Puca, P.(1);Capobianco, I.(1);Petito, V.(1);Masi, L.(1);Fidaleo, M.(2);Del Chierico , F.(3);Palucci, I.(4);Lopetuso, L.R.(1);Laterza, L.(1);Settanni, C.R.(1);Parisio, L.(1);Bibbò, S.(1);Pugliese, D.(1);Armuzzi, A.(1);Pani, G.(5);Gasbarrini, A.(1);Scaldaferri, F.(1);
(1)Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Gastroenterology and Internal Medicine, Rome, Italy;(2)Università La Sapienza, Department of Biology and Biotechnologies "Charles Darwin", Rome, Italy;(3)Children Hospital Bambino Gesù IRCCS, Unit of Human Microbiome, Rome, Italy;(4)Fondazione Policlinico Universitario A. Gemelli IRCCS, Department of Microbiology, Rome, Italy;(5)Catholic University of the Sacred Heart, Department of Translational Medicine, Rome, Italy;
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).