P506 Increased risk of anti-drug antibodies to a second anti-TNF in patients who developed antibodies to the first anti-TNF

Abstract Background Evidence regarding predisposition to develop anti-drug antibodies to a second anti-TNF in patients with inflammatory bowel diseases (IBD) who previously developed antibodies to a first anti-TNF (either infliximab or adalimumab) is conflicting. We aimed to assess the rates of such consecutive immunogenicity. Methods The medical records of all patients with IBD followed at the Rabin and Schneider Medical Centers (all ages) from 2014 to 2019, who were treated with an anti-TNF agent were reviewed. Clinical data including age at diagnosis, gender, disease type, concomitant use of immunomodulators, as well as drug trough levels (TLs) and anti-drug antibodies (ADAs) for both agents were registered. Patients who switched from one anti-TNF to another and had comprehensive clinical and pharmacokinetic data were assessed for consecutive immunogenicity. Results Overall, 1570 patients were tested for TLs and ADAs (infliximab, n = 702, 45%). Rates of positive infliximab ADAs were 31%, and positive adalimumab ADAs were 13%. We identified 55 eligible patients (Crohn’s disease = 52, ulcerative colitis = 2, IBD unclassified = 1; females = 26 [47%]; mean age at diagnosis 26.5 ± 13 years). Of 29 patients with infliximab as the first anti-TNF, 25 (86%) had positive ADAs. None of the 4 patients without ADAs against infliximab developed ADAs against consequent adalimumab, whereas 7/25 (28%) of patients with positive ADAs against infliximab developed ADAs against adalimumab, significantly higher than the overall immunogenicity rate of adalimumab (28% vs. 13%, p = 0.03). Of the 26 patients who were switched from adalimumab to infliximab, 10 (38%) had positive ADAs. Out of 16 patients with negative ADAs against adalimumab, 5 (31%) developed ADAs against consequent infliximab whereas 7/10 (70%) of patients with positive ADAs against adalimumab developed ADAs against infliximab, significantly higher than the overall immunogenicity rate of infliximab (70% vs. 31%, p = 0.008). The overall rate of immunogenicity against the second anti TNF following a switch due to immunogenic failure was 39%. Only 33% of patients were treated with concomitant immunomodulators after an immunogenicity driven switch. Clinical data, as well as TLs and ADA, were comparable in children and adults. Conclusion The rate of consecutive immunogenicity in anti-TNF treated patients is significantly higher than the overall immunogenicity against the first anti-TNF. This higher rate of consecutive immunogenicity may be associated with a predisposition to developing anti-drug antibodies to anti-TNF agents. It may also be a consequence of the relatively low rates of combination therapy following an immunogenic failure.