Anti-drug antibodies against anti-TNF in patients with inflammatory bowel disease: an evaluation of possible strategies.

Immunogenicity against anti-TNF antibodies usually leads to loss of response. We aimed to evaluate the efficacy of clinical strategies to improve clinical remission and pharmacokinetics upon detection of anti-drug antibodies (ADA). Inflammatory bowel disease (IBD) patients with ADA against infliximab or adalimumab were identified through a single centre database search covering 2004-2022. Criteria for successful intervention upon ADA detection (baseline) were clinical remission after 1 year without further change in strategy. Two-hundred-and-fifty-five IBD patients (206 Crohn's disease) were identified. At baseline, median ADA level was 77 AU/ml; 50.2% of patients were in clinical remission. Implemented strategies were: (1) 81/255 (32%) conservative management, (2) 102/255 (40%) anti-TNF optimisation, (3) 72/255 (28%) switch within or out of class. Switching was the most successful strategy for clinical remission (from 19% at baseline to 69% at 1 year, Switching therapy, within or out of class, is the most successful strategy to regain and maintain clinical remission upon immunogenicity. When switching to another anti-TNF, concomitant immunomodulatory therapy should be started or continued to prevent repeated immunogenic loss of response. Anti-TNF dose escalation with concomitant immunomodulator optimisation is the fastest and most effective strategy to suppress ADA. Immunogenicity against anti-TNF antibodies is associated with loss of response in patients with inflammatory bowel diseases and remains a clinical challenge. We investigated potential therapeutic strategies in a retrospective patient cohort focusing on clinical efficacy and pharmacokinetics.