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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, 1Sheba Medical Center, Telhashomer, Israel, 2Rambam 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 anti-TNF activity (Figure 1b for 2 exemplary patients).

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.

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).

Conclusion

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.