- Email: [email protected]
P511 Epstein-Barr Virus in inflammatory bowel disease – correlation with different therapeutic regimens
Clinical: Therapy and observation P511 Epstein-Barr Virus in inflammatory bowel disease correlation with different therapeutic regimens F. Magro1 *, J. Santos-Antunes1 , A. Albuquerque1 , F. Vilas-Boas1 , G.N. Macedo2 , N. Nazareth2 , S. Lopes1 , J. Sobrinho-Sim˜ oes3 , S. Teixeira3 , C. Camila-Dias4 , J. Cabral5 , A. Sarmento2 , G. Macedo1 . 1 Centro Hospitalar S. Jo˜ ao, Gastroenterology, Porto, Portugal, 2 CEBIMED Biomedicine Research Center, Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal, 3 Centro Hospitalar S. Jo˜ ao, Clinical Pathology Department, Porto, Portugal, 4 Faculty of Medicine, University of Porto, CIDES Department of Health Information and Decision Sciences, Porto, Portugal, 5 Faculty of Medicine, University of Porto, Institute of Pharmacology and Therapeutics, Porto, Portugal Background: Epstein-Barr Virus (EBV) is a ubiquitous virus related to several malignancies, namely lymphoma; its prevalence in IBD patients and its relation with different therapeutic regimens are not well studied. Methods: Patients were consecutively enrolled for participation, and healthy volunteers were recruited as controls. EBVDNA was measured at least one time in each patient. Results: Three hundred and seventy nine individuals were enrolled (93 treated with 5-Aminosalicylates, 91 with Azathioprine, 70 with Infliximab, 43 with combined treatment with Infliximab and Azathioprine, and 82 controls). More than 90% of the patients had previous EBV exposure. EBV-DNA was found in 132 samples (35%); its prevalence was significantly higher in every group of IBD patients, comparing to controls. Among IBD patients, Infliximab (with or without Azathioprine) was related to higher prevalence of EBV comparing to Azathioprine alone or 5-Aminosalicylates (p < 0.05). Age above 60 years was related to EBV-DNA positivity with a specificity of 92%. Concerning treated groups, Ulcerative Colitis was the only risk factor identified for high levels of EBV-DNA (>1000 and 2500 copies/mL). No relation was found between EBV and C-reactive protein. Conclusions: IBD is a risk factor for the presence of EBV-DNA in blood, mainly in older patients and in those taking Infliximab. C-reactive protein was not related to EBV DNA prevalence.
S215 Conclusions: This preliminary report suggests that adding immuno-modulators may re-establish clinical response after immunogenic loss of response to infliximab via ATI elimination and restoration of effective anti-TNF blockade.
Figure 1a. Concentrations (Y-axis) obtained by serial measurements of Infliximab level (solid markers) and anti-infliximab antibodies (ATI) levels (hollow markers) in two exemplary patients before and after the addition of an immunomodulator.
P512 Elimination of detectable anti-infliximab antibodies and reversal of loss of response by the addition of an immuno-modulator S. Ben-Horin1 *, M. Waterman2 , U. Kopylov1 , M. Yavzori1 , O. Picard1 , E. Fudim1 , H. Awadie2 , B. Weiss1 , Y. Chowers2 . 1 Sheba Medical Center, Telhashomer, Israel, 2 Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel Background: Therapeutic options for IBD patients with immunogenic loss of response to infliximab are limited. We investigated if addition of immune-modulators after development of antibodies to infliximab (ATI) can eliminate drug-sensitization and restore the clinical response. Methods: A retrospective study of ATI positive patients who lost response to infliximab and who were treated by the addition of immuno-modulator. Serial serum measurements of infliximab and ATI levels were performed and anti-TNF activity of serum was assessed by ELISA-based competition assays before and after immunomodulators’ addition. Results: Five patients were treated by addition of an immunomodulator (azathioprine/6MP 3, Methotrexate 2). Adding the immunomodulator resulted in gradual elimination of ATI and re-emergence of measurable infliximab trough levels in all five patients (shown for 2 exemplary patients in Figure 1a). Clinical response was also restored in all patients. Competition assays showed that immunomodulator-induced elimination of ATIs was accompanied by restoration of effective serum antiTNF activity (Figure 1b for 2 exemplary patients).
Figure 1b. Anti-TNF activity of sera assessed by measuring TNF content in O.D (optical density) after pre-incubation of exogenous graded concentrations of rTNF with sera of patients obtained either during loss of response (triangles line) or 3 months after the addition of azathioprine (squares line).
S215 Conclusions: This preliminary report suggests that adding immuno-modulators may re-establish clinical response after immunogenic loss of response to infliximab via ATI elimination and restoration of effective anti-TNF blockade.
Figure 1a. Concentrations (Y-axis) obtained by serial measurements of Infliximab level (solid markers) and anti-infliximab antibodies (ATI) levels (hollow markers) in two exemplary patients before and after the addition of an immunomodulator.
P512 Elimination of detectable anti-infliximab antibodies and reversal of loss of response by the addition of an immuno-modulator S. Ben-Horin1 *, M. Waterman2 , U. Kopylov1 , M. Yavzori1 , O. Picard1 , E. Fudim1 , H. Awadie2 , B. Weiss1 , Y. Chowers2 . 1 Sheba Medical Center, Telhashomer, Israel, 2 Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel Background: Therapeutic options for IBD patients with immunogenic loss of response to infliximab are limited. We investigated if addition of immune-modulators after development of antibodies to infliximab (ATI) can eliminate drug-sensitization and restore the clinical response. Methods: A retrospective study of ATI positive patients who lost response to infliximab and who were treated by the addition of immuno-modulator. Serial serum measurements of infliximab and ATI levels were performed and anti-TNF activity of serum was assessed by ELISA-based competition assays before and after immunomodulators’ addition. Results: Five patients were treated by addition of an immunomodulator (azathioprine/6MP 3, Methotrexate 2). Adding the immunomodulator resulted in gradual elimination of ATI and re-emergence of measurable infliximab trough levels in all five patients (shown for 2 exemplary patients in Figure 1a). Clinical response was also restored in all patients. Competition assays showed that immunomodulator-induced elimination of ATIs was accompanied by restoration of effective serum antiTNF activity (Figure 1b for 2 exemplary patients).
Figure 1b. Anti-TNF activity of sera assessed by measuring TNF content in O.D (optical density) after pre-incubation of exogenous graded concentrations of rTNF with sera of patients obtained either during loss of response (triangles line) or 3 months after the addition of azathioprine (squares line).