P787 Subcutaneous infliximab in IBD patients with previous immunogenic failure of intravenous infliximab
Husman, J.(1)*;Matthes, K.(1);Gilger, M.(1);Arsova, M.(1);Schmidt, A.(1);Hampe, J.(1);Zeißig, S.(1);Schmelz, R.(1);
(1)University Hospital Dresden- Technische Universität TU Dresden, Department of Medicine I, Dresden, Germany;
Background
The immunogenicity of infliximab (IFX) is a major reason for secondary loss of response to intravenous (IV) IFX treatment. A lower incidence of anti-drug antibodies (ADA) with subcutaneous (SC) IFX treatment compared to IFX IV has been described1,2. Furthermore, data on four patients with immunogenic failure or allergic reactions to IFX IV documented safety of exposure to IFX SC3. Here, we analyzed the efficacy and safety of IFX SC in IBD patients with previous immunogenic/allergic failure to IFX IV in a monocentric analysis conducted at the Dresden University Hospital.
Methods
Immunogenic failure was defined as presence of ADA and low/undetectable IFX trough levels during IFX IV therapy. Patients received IFX SC 120 mg every other week (EOW). HBI and partial Mayo, IFX trough levels, free ADA, and fecal calprotectin (FCP) were determined at wk 0 and wk 12. Clinical remission was defined as HBI<5 or partial Mayo≤1. FCP<250ug/g was considered biochemical remission.
Results
Ten patients (7/10 with active IBD and 3/10 in remission) were included. All patients had previously developed ADA during IFX IV treatment. Two patients had suffered an IFX infusion-related allergic reaction. Baseline demographic parameters are shown in table 1. Patients were extensively pretreated (5/10 had previous treatment with ≥3 biologics). 5/10 patients were switched from ongoing IV application to IFX SC, while 5/10 were started on IFX SC without IFX IV induction. During follow up, 6/10 patients did not reach IFX trough levels≥3ug/ml, of whom four patients showed detectable ADA. 2/10 patients developed mild injection site reactions. No severe immediate hypersensitivity reactions were observed. Treatment persistence across wk 12 was 70% (7/10), while 3/10 patients discontinued IFX SC due to lack of efficacy. In the active IBD group, clinical remission at wk 12 was achieved in 1/7 patients. 2/7 patients showed a decrease in FCP from baseline to wk 12. Among the three patients who entered the study in remission, all maintained clinical and biochemical remission until wk 12 (3/3). 
Conclusion
In this cohort, exposure of patients with previous immunogenic/allergic failure of IFX IV was well tolerated and safe. However, only a minority of patients established significant IFX through levels with EOW IFX SC therapy and clinical responses were heterogeneous. Further studies are required to assess the safety and efficacy of IFX SC in patients with previous immunogenic IFX failure and to investigate the value of dose intensification and/or interval shortening of IFX SC in this patient population.
References
1 Smith et al, J Crohn Colitis, 2022
2 Schreiber et al, Gastroenterol, 2021
3 Caron et al, Aliment Pharmacol Ther, 2022