P656. Fcgamma Receptor Type IIIa polymorphisms and their correlation with clinical outcome in patients with inflammatory bowel disease during a long term follow up
G. Bodini1, V. Savarino1,2, P. Dulbecco1,3, I. Baldissarro1,2, E. Savarino1,4,5, 1IRCCS San Martino Genova, Dipartimento di medicina interna, Genova, Italy, 2Universita di Genova, Dipartimento di medicina interna, Genova, Italy, 3Università di Genova, Dipartimento di Medicina Interna, Genova, Italy, 4University of Padua, Department of Surgery, Oncology and Gastroenterology, padova, Italy, 5Department of Surgery, Oncology and Gastroenterology, University of Padua, Gastroenterology Unit, Padua, Italy
A total of 20–30% of patients with active Crohn's disease (CD) do not respond to anti-TNFalfa treatments and up to 40% of patients in chronic therapy experience a loss of response. Furthermore about 50% of patients with ulcerative colitis (UC) experience a loss of response to anti-TNFalfa therapy after one year. The cause of this limited efficacy is unclear, but past studies hypothesized that the individual variation of drug metabolism may play an important role. Thus, given the limited data available, the role of FcgammaIIIa receptor (i.e. one of the four receptors involved in the catabolic pathway of anti-TNF-alfa drugs) polymorphisms should be further explored.
Aim: The aim of this prospective, long-term follow up study was to evaluate the correlation between FcgammaIIIa receptor polymorphisms and clinical outcome in IBD patients undergoing biologic therapy.
We enrolled consecutive IBD patients who achieved clinical remission by anti-TNFalfa therapy. Blood samples were collected at the beginning of biological therapy. The assessment of IBD activity was based on the Harvey–Bradshaw Index score (HBI, remission <5, mild disease 5–7, moderate disease 8–16, severe disease >16) for CD patients and on the Mayo score (Mayo <2 remission, mild disease 2–5, moderate/severe disease 6–12) for UC patients. Biochemical evaluation and clinical score were assessed every 8 weeks. For the genotyping analysis we used a Light Snips (Tib-Molbiol, Genova, Italy) and the Real-Time PCR Technique developed by Light Cycler 480 Instrument (Roche, Mannheim, Germany).
We prospectively included 39 patients (12UC/27 CD, 16F/23M) with a median follow-up of 66.8 weeks (10–112). A total of 25 (64.1%) (10UC/15CD) patients kept in remission during the whole follow up period, while 14 (35.9%) (2UC/12CD) experienced disease relapse. As shown in the Table, four out of 14 (28.6%) (1UC/3CD) patients who experienced disease relapse, had FcgammaIIIa-158 V/V receptor polymorphism, while the remaining 10 (71.4%) (9CD/1UC) had Fc gammaIIIa-158 F/V or F/F receptor polymorphisms. Out of 25 patients who kept in remission, 3 (12%) (1CD/2UC) had FcgammaIIIa-158 V/V receptor polymorphism, whereas the remaining 22 (88%) (14CD/8UC) showed FcgammaIIIa-158 F/V or F/F receptor polymorphisms. Patients in remission tended to have more often FcgammaIIIa-158 V/V receptor polymorphism compared to patients who relapsed, but statistical significance was not reached.
The evaluation of FcgammaIIIa-158 V/V receptor polymorphism does not seem useful in identifying patients who are more likely to lose anti TNF-alfa response during a long term period. However, further larger studies are necessary to investigate the role of FcgammaIIIa receptor polymorphisms.