Dynamics of serum concentrations of antibodies to infliximab: a new approach for predicting secondary loss of response in inflammatory bowel diseases

Background: Antibodies to infliximab (ATI) in serum are associated with secondary loss of response (LOR) to infliximab (IFX) therapy in patients with inflammatory bowel disease (IBD). However, feasible ATI-related predictors of therapy success are lacking and knowledge about individual ATI dynamics is limited. Therefore, this study analyzed whether ATI dynamics are able to predict LOR to IFX therapy and compared their predictive power with known predictors of LOR to IFX. Methods: This was a retrospective study of patients with Crohn’s disease (CD) or ulcerative colitis (UC) on IFX maintenance therapy and proactive IFX and immunogenicity monitoring in an outpatient clinic in Germany. Slopes of ATI (S_ATI) and IFX levels (dynamic parameters) and medians of ATI, IFX, C-reactive protein, and fecal calprotectin (static parameters) were calculated over a defined period of time after ATI emergence. Dynamic and static parameters were analyzed for associations with end points infliximab discontinuation due to secondary LOR and total IFX discontinuation. Results: In all, 500 visits from 38 IBD patients (28 CD, 10 UC) with a median IFX maintenance duration of 68.2 weeks were evaluated. Grouping by S_ATI (ATI-N = ATI nondetectable, ATI-↓ = negative S_ATI, ATI-↑ = positive S_ATI) yielded significant differences for outcomes LOR (p = 0.004) and total IFX discontinuation (p = 0.01). Patients in the ATI-↓ group survived significantly longer LOR-free compared with the ATI-↑ group (p = 0.02). Cox regression confirmed S_ATI to be a significant risk factor for LOR (p = 0.002). An S_ATI cut-off of approximately 2.0 AU mL⁻¹ week⁻¹ was determined to predict LOR with 83.3% sensitivity and 93.8% specificity. Conclusion: The ATI slope-based index S_ATI is a new feasible diagnostic predictor of LOR in IBD patients. S_ATI may facilitate quick therapeutic decisions after ATI emerge.