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PHC-017 PHARMACOGENETIC STUDY ABOUT INFLUENCE OF A POLYMORPHISM IN GENE TRAILR1 IN RESPONSE TO INLFIXIMAB IN PATIENTS WITH CROHN’s DISEASE (CD)
  1. M de Andrés Bautista1,
  2. D Lacruz Guzmán1,
  3. V Dominguez Leñero2,
  4. P Pérez Cañadas1,
  5. M Martinez Penella1,
  6. H Garcia Lagunar1,
  7. E Ferris Villanueva1,
  8. R Guerrero Bautista1
  1. 1Hospital Universitario Santa Lucia, Farmacia, Murcia, Spain
  2. 2Hospital Perpetuo Socorro, Farmacia, Murcia, Spain

Abstract

Background Anti-TNF drugs show high inter-individual variability in efficacy and toxicity.

Currently there are no genetic, biochemical or environmental markers to predict response to treatment.

Purpose To assess the influence of gene polymorphism rs2230229 TRAILR1 as a genetic marker in response to treatment with infliximab in patients diagnosed with Crohn’s disease (CD). Will it enable us to predict response and improve the effectiveness of the drug?

Materials and Methods Prospective observational study of all patients diagnosed with CD treated with infliximab at our hospital. The assessment of response to infliximab was performed using as criteria of clinical response a decreased questionnaire score CDAI (Crohn Disease Activity Index) at the 4th dose. Subsequently patients were considered to have responded if their CDAI decreased by 70 points or more with respect the baseline and at least 25% on the total score and clinical remission was achieved by a CDAI of less than 150 points. Biological response criteria were defined such as patient responders, partial responders or non-responders according to variation in levels of C-reactive protein (CRP) with regard to baseline at 3, 6 and 12 months. To detect polymorphism KASPAR probes were used in a PCR-based allele-specific competitive FRET technology using a computer and a real time PCR of Aplied Biosystems 7500F in 96-well plate. All patients included in the study received a starting dose of infliximab 5 mg/kg at 0, 2 and 6 weeks after the start and then a maintenance dose every 8 weeks. Statistical analyses were performed with Epidat 3.1 and the level of significance was indicated by a p value of less than 0.05.

Results The study included a total of 40 patients. The mean age of the patients was 38.66 ± 13.98 years and 61.1% were female. The distribution for genotypes was 81.6% AA, 15.8% GA and 2.6% GG. Significant correlation wasn’t found between genotypes or alleles of this polymorphism and clinical response to infliximab. Instead, statistically significant differences were shown for approximately 6 months of treatment when comparing patients with genotypes GG and GA/AA and a positive response (p = 0.047) when considering the biological response. Similarly patients with a G allele had a more frequent negative response than those with the A allele (p = 0.043). On the other hand, significant correlation was found between patients carrying the A allele and the positive response, at 3, 6 and 12 months based on biological response distribution.

Conclusions The results of our study show an association of this polymorphism with response to infliximab. Worst response rates are observed in patients carrying allele G diagnosed with CD. We need more studies on this polymorphism and with a larger sample size to confirm these findings.

No conflict of interest.

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