Background and Importance Loss of response to infliximab and adalimumab therapy may occur due to development of neutralising anti-drug antibodies (ADA), leading to treatment failure in inflammatory bowel disease (IBD).

Aim and Objectives To assess the immunogenicity of infliximab and adalimumab in adults and paediatric IBD patients, along with therapeutic approach and potential factors contributing ADA development.

Material and Methods Retrospective observational study in adult and paediatric IBD patients treated with infliximab and adalimumab, between January 2019 to June 2023.

Adalimumab, infliximab and ADA concentrations were determined by enzyme immunoassays. Concretely, ADA if patients had infliximab ≤3 mcg/ml and adalimumab ≤5mcg/ml concentrations (drug-sensitive assay). Standard dosage regimen (SD): adalimumab 40 mg/14 days, Infliximab 5 mg/kg/8 weeks; intensified dosage involved either shortening the interval or increasing dose.

Results 659 patients were included. Specifically, 399 (60.5%) received adalimumab: 24 (6.0%) paediatrics and 375 (94.0%) adults; and 260 (39.5%) received infliximab: 36 (13.8%) paediatrics and 224 (86.2%) adults.

Adalimumab antibodies (AAA) were evaluated in 412 samples from 195 (48.9%) patients [10 (5.1%) paediatrics and 185 (94.9%) adults] and infliximab antibodies (ATI) were evaluated in 377 samples from 150 (57.7%) patients [19 (12.7%) paediatrics and 131 (97.3%) adults].

Thirteen (3.3%) patients developed AAA: all were adults with Crohn’s disease and mean age of 40.6 (12.9) years, including 7 (53.8%) females. Seven (53.8%) patients had been on adalimumab for <1 year. At the time of AAA detection, five (38.5%) patients had adalimumab SD, and six (46.2%) receiving immunosuppressants. Eleven (84.6%) patients discontinued adalimumab, while two (15.4%) with AAA of 133ng/ml and 107.9ng/ml underwent adalimumab intensification achieved AAA negativisation. Poor adherence was suspected in five (38.5%) patients.

Twenty-two (8.5%) patients developed ATI: 20 (90.9%) adults with 45.2 (12.8) years, including 8 (40%) females; and 2 (9.9%) paediatrics with 15.0 (5.7) years comprising one (50%) female. IBD diagnosed: Crohn’s disease in 14 (63.6%) and ulcerative colitis in eight (36.4%) patients. Eleven (50%) patients had been on infliximab for <1year. At the time of ATI detection, 12 (54.5%) patients had infliximab SD, and 12 (54.5%) receiving immunosuppressants. Thirteen (59.1%) patients discontinued infliximab, while seven (31.8%) with ATI <30ng/ml and two (9.1%) with 100.6ng/ml and 171.7ng/ml underwent infliximab intensification achieved ATI negativisation. Poor adherence was confirmed in six (27.3%) patients.

Adalimumab and infliximab concentrations were <1mg/ml in all patients with ADA.

Conclusion and Relevance A proportion of IBD patients developed ADA, with a higher incidence observed in those receiving infliximab. Enhancing adherence could reduce the risk of ADA development, and intensifying treatment may be effective in achieving ADA negativisation.

Conflict of Interest No conflict of interest.