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P484. Identification of clinical and genetic predictors of response to therapy in patients with ulcerative colitis (UC)

P. Ferreira1, P. Sousa2, P. Moura Santos2, P. Ministro3, J. de Deus4, L. Tavares2, P. Peixe5, J. Velosa2, M. Brito1, M. Cravo6, 1Escola Superior de Tecnologia da Saúde de Lisboa, Lisboa, Portugal, 2Hospital Santa Maria, Lisboa, Portugal, 3Hospital S. Teotónio, Viseu, Portugal, 4Hospital Fernando Fonseca, Lisboa, Portugal, 5Hospital Egas Moniz, Lisboa, Portugal, 6Hospital Beatriz Ângelo, Loures, Portugal

Background

A third of UC patients are refractory to 5ASA compounds will need immunossupression (IS) and/or biologics. We aimed to identify clinical and genetic predictors of response to therapy in patients with UC.

Methods

We included 159 UC patients, 90 female and 69 males, with a mean age of 47±16.2 yrs and a disease duration of 11±9.4 yrs. Patients were classified as responders based on long term sustained remission lasting at least one year, not needing steroids, surgery or escalation of therapy. Patients' response to therapies is shown in the table.

Clinical and demographic variables were recorded. A total of ten Single Nucleotide Polymorphisms (SNPs) were studied: MDR1C3435T and G2677T/A, IL23RG1142A, C2370A, G43045A and G9T, CASP9C93T, FASG670A, FASLGC844T and ATG16L1A898G. Genotyping was performed by real time PCR, with Taqman Probes.

Results

Individuals with the mutant allele for MDR1G2677T/A were more often diagnosed after 16 yrs (OR6.61 95% CI (1.18–37.01), p = 0.03) and individuals with the mutant allele for MDR1C3435T had the disease for less than 5 years (OR0.34 95% CI (0.15–0.76), p = 0.01). Carriers of the mutant allele for IL23RG43045A had a significantly higher probability of developing extra intestinal manifestations (EIM) (OR3.52 95% CI (1.40–8.84), p = 0.01). Regarding response to therapy we observed that older patients were more prone to respond to 5ASA (0R6.71 95% CI (1.04–43.21), p = 0.05), while those with an extensive disease (E2 and E3) were less likely to respond to 5ASA (OR0.11 95% CI (0.01–0.96), p = 0.05 and OR0.03 95% CI (0.01–0.27), p = 0.001, respectively). Individuals with EIM were more often refractory to 5ASA (OR0.20 95% CI (0.08–0.50), p = 0.001), to azathioprine (OR0.20 95% CI (0.05–0.86), p = 0.03) and corticodependent (OR0.23 95% CI (0.07–0.79), p = 0.02). In respect to genetic predictors of response we found that homozygotes AA for IL23RC2370A were more often corticodependent (OR0.16 95% CI (0.03–0.76), p = 0.02).

 5ASACorticosteroidsAzathioprineBiologics
Responders107492818
Non-responders426196

Conclusion

Besides extension of disease, which has been associated with increased need of IS, the presence of EIM is a marker of refractoriness to 5ASA and azathioprine as well as of corticodependency. IL23R SNPs are not only associated with EIM as well as with corticodependency.

Study supported with grant GEDII 2009–2012.