Anti‐infliximab antibody concentrations can guide treatment intensification in patients with Crohn's disease who lose clinical response

Summary Background The presence of antibodies towards infliximab ( ATI ) is associated with lower infliximab ( IFX ) trough concentrations and loss of response. IFX treatment intensification is effective for restoring response in most, but not all patients with Crohn's disease ( CD ). Aim To compare outcome, pharmacokinetics and immunogenicity of treatment intensification strategies in patients with CD who lost clinical response to IFX . Methods A retrospective cohort study was conducted, including 103 patients with CD who lost clinical response during IFX maintenance therapy and therefore received a double dose IFX (10 mg/kg) and/or a next infusion after a shortened interval. IFX and ATI concentrations were measured in consecutive trough samples, just before (T0) and after (T+1) treatment intensification. Results Clinical response (physicians' global assessment) and biological response and remission ( CRP ) were restored in 63%, 42% and 24% of patients (evaluated at T+1). Treatment intensification increased IFX trough concentrations from 1.2 μg/ mL [0.3‐3.6] at T0 to 3.6 μg/ mL [0.5‐10.2] at T+1 ( P < .0001). Using a drug tolerant assay, ATI were detected in the T0 sample of 47% of patients. ATI negatively impacted the achieved IFX trough concentration (Spearman r −0.57, P < .0001) and the probability of clinical response ( P = 0.034) at T+1. When ATI were quantifiable but <282 ng/ mL eq. at T0, combined interval shortening and dose doubling was more effective for restoring therapeutic IFX trough concentrations (≥3 μg/ mL at T+1) than dose doubling alone, which in turn was more effective than interval shortening alone ( P < .001). Conclusion Antibodies towards infliximab can guide clinical decision‐making on treatment intensification.