OP0060 CLINICAL CONSEQUENCES OF INFLIXIMAB IMMUNOGENICITY AND THE IMPACT OF THERAPEUTIC DRUG MONITORING: SECONDARY ANALYSES OF A RANDOMISED CLINICAL TRIAL

Background Neutralising anti-drug antibodies (ADAb) are a problem in treatment with TNF-inhibitors (TNFi). Prospective data needed to better understand how ADAb formation impacts safety and outcomes of TNFi. Proactive therapeutic drug monitoring (TDM) allows for timely detection this strategy may have role reducing the negative clinical consequences ADAb. Objectives To explore temporal relation between anti-infliximab antibody adverse events, assess impact TDM as reduce these consequences. Methods Patients immune mediated inflammatory diseases on infliximab therapy (n=615; 181 spondyloarthritis, 120 rheumatoid arthritis, 72 psoriatic 114 ulcerative colitis, 83 Crohns disease 45 psoriasis) were included Norwegian Drug Monitoring (NOR-DRUM) trials (1, 2) randomised or standard therapy. followed 30 52 weeks NOR-DRUM A (induction therapy) B (maintenance trials, respectively. assessed sensitive automated fluorescence assay at each infusion. In sub-study, we risk of; failure achieve remission (analysis A), worsening during maintenance B), discontinuation C) events D) patients developing compared without using logistic- cox regression Kaplan-Meier survival analyses, stratified by Regression analyses adjusted potential confounders (Table 1). Remission defined specific composite scores 2). Results detected 147/615 (24 %) patients. had higher not achieving after initiating (odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.3-4.2, P<0.01) 1, Figure 1A) having (hazard (HR) 2.1, CI 1.4-3.3, P<0.001) (Figure 1B). was significantly associated general, but infusion reactions highly increased (HR 29, 11-78, P<0.001). The positive 6.5, 4.7-8.9, group lower an reaction than 1B C). discontinued more often control 1D). Conclusion Formation led poorer both induction reactions. Early proactive reduced ADAb, effectiveness safety, highlighting optimising TNFi References [1]Syversen SW et al. Jama. 2021;326(23) [2]Syversen 2021;325(17) Table 1. Treatment related Analysis A) Non-remission OR P 2.4 (1.3-4.2) <0.01 1.0 (0.7-1.5) 0.9 B) Disease HR (CI ) 2.1 (1.4,3.2) 0.4 (0.3-0.6) <0.001 Infusion 29 (11-78) 0.3 (0.1-0.7) 6.5 (4.7-8.9) 1.4 (1.0-1.8) 0.03 from multivariable logistic (A)- (B-D) models including covariates: TDM, age, sex, diagnosis, comedication. shown table non-remission week 30, therapy, patents group. Acknowledgements: NIL. Disclosure Interests Marthe Kirkesæther Brun: None declared, Kristin Hammersbøen Bjørlykke Speakers bureau: Janssen, Grant/research support from: Olympus travel grant, Johanna Elin Gehin: David J Warren: Rolf A. Klaasen: Joseph Sexton: Øystein Sandanger: Tore K. Kvien Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, BMS, Galapagos, Cato Mørk Novartis Norway, LEO Pharma, ACO Hud Norge, Cellgene, Abbvie, Galderma Nordic AB, Jørgen Jahnsen Boerhinger Ingelheim, Giliad, Hikma, Janssen Cilag, Orion Roche, Takeda Nils Bolstad: Kaasen Jørgensen Celltrion Norgine, Espen Haavardsholm Boehringer-Ingelheim, Eli Lilly, Guro Løvik Goll Boehringer Silje Watterdal Syversen: declared.