P115 SPECIFIC CYTOKINE PROFILES TO IDENTIFY RESPONSE TO ANTI TUMOR NECROSIS FACTOR α BIOLOGICAL THERAPY IN INFLAMMATORY BOWEL DISEASE. (7th February 2019)

• Record Type: Journal Article
• Authors: Mateos, Beatriz; Saez, Esteban; Moret, Inés; Tortosa, Luis; Cerrillo, Elena; Iborra, Marisa; Nos, Pilar; Beltrán, Belén
• Is Part Of: Inflammatory bowel diseases. Volume 25(2019)Supplement 1
• Page Start: S55
• Page End: S56
• Publication Date: 2019-02-07
• Subjects: Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1093/ibd/izy393.124
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract: Introduction: biological therapies such as anti tumor necrosis factor α (TNFα) drug infliximab (IFX), have led to substantial improvements in the treatment of Crohn's disease (CD) patients. However, approximately a third of them do not have a response during induction period (primary non-response). This fact highlights the clinical need to identify biomarkers that predict response, providing the bases for personalized medicine. Aim: to analyze plasmatic cytokine profiles of active CD patients and their changes after IFX induction therapy. To identify pre-induction cytokine profiles to predict response to IFX. Material and methods: 22 active CD patients were included in the study (45% L1, 68% M), which received an induction therapy of IFX (5mg/kg week 0, 2, 6). Peripherally blood samples (for cytokine analysis) and fecal samples (for fecal calprotectin analysis, FC) were collected on weeks 0 and 14. Plasma interleukins (IL- 1β, -2, -6, -7, -8, -10, -12p70, -13, -17, -21, -22, -23), IFγ, TNFα and OSM concentrations were measured by Luminex technology. CF concentration was measured by ELISA analysis. Response to the treatment was determined by clinical parameter (Harvey-Bradshaw index, HBI) and by the drop of FC based on its logarithm values (Ln [FC] week 0 – Ln [FC] week 14). R statistical software and random forest predictive model were used for data analysis. Results: CF mean and HBI values were 880 ng/g and 6.91; and 440 ng/g and 3.4 (pre and post- treatment respectively). No cytokine was individually correlated to a response to the therapy in week 14. Cytokine correlation analysis (Rho Sperman (R 2 ), correlation from R 2 >0.4) showed R 2 =0.92 between IL-1β and IL-2, R 2 =0.68 between IL-8 and TNFα, R 2 = 0.67 between IL22 and OSM; and R 2 = 0.5 between HBI and IL-8. CF showed no correlation with any cytokine. Random forest model suggests elevated pre-treatment [IL-13], moderate levels of [TNFα] and the presence of [OSM] are significantly associated to a better response to IFX therapy. Conclusions: cytokines are part of high correlated networks, These associations suggest cytokines must be analyzed all together instead of individually. IL-13 and OSM seem optimal cytokines to predict response to the IFX therapy, along with moderate TNF-α. The drop of CF after IFX induction therapy is a useful tool to identify responders better than quantitative value of CF.