Drug Levels Associated with Optimal Discrimination Between Remission and Non-Remission and Comparison of Antibody Assays During First Year of Stable Infliximab Maintenance Therapy in Inflammatory Bowel Disease.

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Ther Drug Monit. 2021 Aug 11; doi: 10.1097/FTD.0000000000000913. Epub 2021 Aug 11.

Drug Levels Associated with Optimal Discrimination Between Remission and Non-Remission and Comparison of Antibody Assays During First Year of Stable Infliximab Maintenance Therapy in Inflammatory Bowel Disease.

Therapeutic drug monitoring

Maria Dorn-Rasmussen, Sine Buhl, Jørn Brynskov, Jakob T Bay, Nils Bolstad, Tobias W Klausen, David J Warren, Mark A Ainsworth, Casper Steenholdt

Affiliations

Department of Gastroenterology, Copenhagen University Hospital Herlev, Denmark (DK) Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, DK Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway Department of Hematology, Copenhagen University Hospital Herlev, DK Department of Gastroenterology, Odense University Hospital, DK.

PMID: 34387220 DOI: 10.1097/FTD.0000000000000913

Abstract

BACKGROUND: In order to implement therapeutic drug monitoring (TDM)-based strategies for infliximab (IFX) in inflammatory bowel disease (IBD), the authors assessed IFX levels for optimal discrimination between remission and non-remission and compared assays for anti-IFX antibodies (Abs).

METHODS: The retrospective cohort comprised 163 bionaïve patients with IBD who received stable IFX maintenance therapy (5 mg/kg every 8 weeks [q8w]) for one year. The clinical and biochemical remission status was assessed at all infusions (weeks 14-22-30-38-46-54), and IFX and anti-IFX Abs were estimated using a time-resolved fluorometric assay (n=690; 88% of infusions). Samples positive for anti-IFX Abs or IFX levels

RESULTS: At all assessed time points, IFX levels were more than double in patients presenting clinical or biochemical remission. An IFX concentration of 4.5 µg/mL was associated with clinical remission during the entire first year of therapy (sensitivity 54% [49-59], specificity 73% [67-78], AUCROC 0.65 [0.60-0.69], p<0.0001); these values were comparable with biochemical remission. Exploratory assessments for endoscopic remission (n=131) were performed at the discretion of the treating physician. Anti-IFX Abs were associated with undetectable IFX and treatment failure (OR 2.9 [1.4-6.0], p<0.01), irrespective of persistency or transiency. All performed assays detected anti-IFX Abs in [SWUNG DASH]2/3 of samples. Binding assays demonstrated a higher sensitivity to anti-IFX Abs.

CONCLUSION: IFX at [SWUNG DASH]5 µg/mL was associated with clinical and biochemical remission during the first year of maintenance therapy. During this phase of therapy, standard binding assays are appropriate for TDM.

Conflict of interest statement

Conflicts of Interests: Within the last two years, S Buhl has served as a speaker for Janssen and Takeda Pharmaceutical Company and as a consultant for Takeda Pharmaceutical Company. J Brynskov has se

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