Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients

Ilana Reinhold; Sena Blümel; Jens Schreiner; Onur Boyman; Jan Bögeholz; Marcus Cheetham; Gerhard Rogler; Luc Biedermann; Michael Scharl

doi:10.1159/000511296

Clinical Relevance of Anti-TNF Antibody Trough Levels and Anti-Drug Antibodies in Treating Inflammatory Bowel Disease Patients

Inflamm Intest Dis. 2021 Feb;6(1):38-47. doi: 10.1159/000511296. Epub 2020 Nov 20.

Authors

Ilana Reinhold^{1

2}, Sena Blümel¹, Jens Schreiner³, Onur Boyman^{3

4}, Jan Bögeholz^{1

2}, Marcus Cheetham², Gerhard Rogler^{1

4}, Luc Biedermann¹, Michael Scharl¹

Affiliations

¹ Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
² Department of Internal Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³ Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
⁴ Faculty of Medicine, University of Zurich, Zurich, Switzerland.

Abstract

Background and aims: The majority of patients treated with anti-tumor necrosis factor (TNF) therapy develop anti-drug antibodies (ADAs), which might result in loss of treatment efficacy. Strict guidelines on measuring trough levels (TLs) and ADA in clinical routine do not exist. To provide real-world data, we took advantage of our tertiary inflammatory bowel disease (IBD) center patient cohort and determined indicators for therapeutic drug monitoring (TDM) and actual consequences in patient care.

Methods: We retrospectively collected clinical data of 104 IBD patients treated with infliximab or adalimumab in our IBD clinic. Patients with TL and ADA measurements between June 2015 and February 2018 were included.

Results: The main reason for determining TL was increased clinical disease. Subtherapeutic TLs were found in 33 patients, therapeutic TLs in 33 patients, and supratherapeutic TLs in 38 patients. Adjustments in anti-TNF therapy occurred more frequently (p = 0.01) in patients with subtherapeutic TL (24 of 33 patients; 73%) as compared to patients with therapeutic and supratherapeutic TLs (26 of 71 patients; 37%). No correlation could be found between TL and disease activity (p = 0.16). Presence of ADA was found in 16 patients, correlated with the development of infusion reactions (OR: 10.6, RR: 5.4, CI: 2.9-38.6), and was associated with subtherapeutic TL in 15 patients (93.8%). Treatment adaptations were based on TL and/or ADA presence in 36 of 63 patients.

Conclusions: TDM showed significant treatment adaptations in patients with subtherapeutic TL. Conversely, in patients with therapeutic and supratherapeutic TLs, reasons for adaptations were based on considerations other than TL, such as clinical disease activity. Further studies should focus on decision-making in patients presenting with supratherapeutic TL in remission.

Keywords: Adalimumab; Anti-drug antibodies; Anti-tumor necrosis factor; Crohn's disease; Inflammatory bowel disease; Infliximab; Trough level measurement; Ulcerative colitis.