Su1292 Biomarker Panel for Prediction of Mucosal Healing in Patients With Crohn's Disease Under Infliximab Therapy

Introduction.Infliximab has led to new therapeutic goals in Crohn's disease (CD) such as complete mucosal healing and improvement of quality of life.The current standard for assessing mucosal healing is endoscopy.However, frequent assessments are costly and uncomfortable to the patient.Non-invasive, accurate surrogate serum markers would therefore be welcomed to aid clinicians in predicting mucosal healing.Methods.In a retrospective study, 119 CD patients who started infliximab and who underwent serial endoscopies (before and during infliximab) were included.Serum samples were available at the time of endoscopy and levels of markers were correlated with the degree of healing (not healed, marked improvement or complete healing).Thirty-five biomarkers were measured in 181 serum samples with the use of CEER, a proprietary highly sensitive protein micro-array, or homogenous mobility shift assays (Prometheus Laboratories Inc., San Diego, CA).These markers included growth and repair factors, pro -and anti-inflammatory markers and the IBD SGI serology panel.Infliximab and antibodies to infliximab were also measured.Clinical information regarding age at sampling, gender, age at diagnosis, location of disease, anal involvement and previous surgery was included.For statistical analysis SPSS and R were used.Results.From the 119 CD patients, 64 CD patients showed complete healing with no relapse, whereas 55 CD patients never showed mucosal healing.Univariate analyses indicated that age and 12 serum markers (HGF, BTC, TWEAK, CRP, ICAM, SAA, VCAM, IL-2, IL-8, IFN-γ, IL-6 and IL-10) were significantly associated with mucosal healing (p<0.1).Selection of the best subset of predictors through multiple logistic regression analysis retained age [Odds ratio 0.97 (95% confidence interval 0.94-0.99),p=0.010],HGF [0.86 (0.79-0.94), p=0.001],BTC [1.24 (1.07-1.43),p=0.003],TWEAK [1.04 (1.01-1.07),p=0.014] and VCAM [0.93 (0.87-0.98), p=0.012] as independent predictors based on Bayesian information criterion and the results remained significant after bootstrapping.A cumulative prediction score was developed by combining the 5 prediction factors (Age<29.5 years, HGF<11.42CU/ml, BTC>11.44 CU/ml, TWEAK>20.62CU/ml and VCAM<4200 μg/ml) which resulted in a significant and gradual increased prediction of mucosal healing (Figure 1, linear-by-linear p<0.001). Conclusion.We have identified 1 clinical parameter and 4 serum markers as independent predictors of mucosal healing.All serum markers play a role in the pathogenic mechanisms of CD.HGF has a central role in angiogenesis and tissue regeneration, BTC is a member of the EGF family of growth factors, TWEAK is a cytokine that has overlapping signaling functions with TNF and VCAM is a cell-adhesion molecule.The combined biomarker panel could facilitate prediction of mucosal healing in the future.