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P504. Familial aggregation in the response to anti-TNF in inflammatory bowel disease patients

T. Billiet1, I. Cleynen2, V. Ballet2, M. Ferrante2, K. Van Steen3, P. Rutgeerts2, S. Vermeire2, 1KU Leuven, IBD Group, Leuven, Belgium, 2KU Leuven, IBD Group, Belgium, 3ULG, Montefiore Institute / Bioinformatics – Statistical Genetics, Belgium

Background

The introduction of anti-TNF antibodies has greatly improved outcomes for patients with inflammatory bowel disease (IBD). In clinical practice response to anti-TNF is seen in >80% of patients, although 10–15% are non-responders. The latter is believed to be at least partially explained by genetic factors. Through the immunochip project 163 susceptibility loci for IBD have been confirmed and efforts are underway to link these factors to response or adverse events to drugs. At current, nothing is known on response to anti-TNF within families. We therefore investigated if there is a familial aggregation of response to adalimumab (ADA) or infliximab (IFX).

Methods

From our database we identified 74 patients belonging to 34 families that received IFX, ADA or both. This comprised of 28 first degree (parent, child and sibling) and 19 second or higher degree pairs. We studied if the primary response to anti-TNF shows concordance among family members. Clinical response was assessed at week 4 or 10 after a single infusion or induction schedule, respectively. Patients who had clinical improvement with an obvious decrease of the disease were considered as responders. Those who had no benefit after two or three infusions were considered as primary non-responders. We also analyzed the disease location and behavior for each pair.

Results

Overall, 63 (85%) patients showed response and 11 (15%) non-response. No significant difference was observed in response rate between IFX or ADA treated patients. In 87% of pairs we found concordance for response (79%) or non-response (8%). If we considered first degree pairs only, the concordance rate increased to 93% compared to 79% in second and higher degree pairs. Among the 22 first degree pairs with response concordance, 15 or 68% also shared disease location.

Conclusion

A high rate of familial aggregation for response to anti-TNF was observed in this cohort of IBD patients. To our knowledge this has never been investigated in any inflammatory disease before. The fact that the concordance was even higher in first degree relative pairs as compared to second and further degree pairs strengthens the hypothesis that response to anti-TNF therapy could in part be driven by genetic factors. In this respect, the immunochip project could be used to identify underlying genetic factors responsible for response to anti-TNF. This is an ongoing project of the IIBD-GC.