The Impact of Intermediate Antidrug Antibodies to Infliximab and Adalimumab on Clinical Outcomes in Patients with Crohn’s Disease or Ulcerative Colitis

Abstract

Background: The anti-TNF drugs adalimumab (ADA) and infliximab (IFX) are effective treatments for inflammatory bowel disease (IBD). However, 40% of patients lose response, often due to the development of antibodies-to-ADA (ATA) and antibodies-to-IFX (ATI). While low ATA/ATI titres (less than 200 ng/mL) are associated with better outcomes and high ATA/ATI titres (>1,000 ng/mL) are associated with poorer outcomes, the significance of intermediate ATA/ATI titres (200–999 ng/mL) is not well understood. This study aims to investigate the impact of intermediate ATA/ATI titres on outcomes in patients with IBD. Methods: A retrospective chart review of 376 patients with IBD was conducted. The primary clinical outcome was persistence on anti-TNF therapy for 1 year after the measurement of ATA/ATI titres. The participants consisted of patients with IBD treated with IFX or ADA at the University of Maryland Medical Center’s Inflammatory Bowel Disease Program between October 2016 and October 2019. Results: Out of 322 patients with low titres, 271 persisted on their original anti-TNF, compared with nine out the 15 patients with intermediate titres (p=0.026) and one out the 10 patients with high titres (p less than 0.0001). The odds ratio of persistence when comparing intermediate titres to low titres was 0.26 (0.09–0.80), and when comparing high titres to low titres was 0.02 (0.00–0.14). Conclusion: Patients with intermediate titres were more likely to lose response to anti-TNF drugs and require a change in anti-TNF therapy than patients with low titres. Although the sample size of patients with intermediate titres was small, providers should consider dose optimisation of anti-TNF drugs, with or without the addition of an immunosuppressant, when intermediate titres are present.