OP0301 RISK FACTORS FOR ANTI-INFLIXIMAB ANTIBODY FORMATION: RESULTS FROM THE RANDOMISED CONTROLLED NOR-DRUM A TRIAL

Background: Immunogenicity is related to loss of efficacy and safety TNFα inhibitors frequently observed early in the treatment course. The highest rate anti-drug antibody (ADAb) formation has been reported for infliximab (IFX). 1 Knowledge about risk factors immunogenicity might contribute better handling this problem clinical practice. Objectives: To identify ADAb during phase IFX treatment. Methods: 411 patients with immune-mediated inflammatory diseases (84 rheumatoid arthritis (RA), 119 spondyloarthritis (SpA), 45 psoriatic arthritis, 83 ulcerative colitis, 58 Crohn’s disease 22 psoriasis) initiating were included 38-week NOR-DRUM A trial randomised 1:1 therapeutic drug monitoring or standard therapy. 2 primary endpoint was remission at week 30. Serum (s) levels measured each infusion by in-house assays; time-resolved fluorometric assay sIFX inhibition ADAb. In sub-study, possible including demographic variables, diagnosis, comedication, activity, dose, holidays, assessed using logistic regression. Variables a p-value <0.25 univariate analyses further examined multivariate adjusting potential confounders (diagnosis, age gender). Results: 410 had least one measurement present analyses. 76% biologic-naive 45% (18% RA patients) used as monotherapy. Patients received mean dose 3.2-5.9 mg/kg (RA 3.2 mg/kg). detected 78 (19%) patients. Table shows variables significant association development. Analyses revealed an increased development (Odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-3.9), while SpA lower (OR 0.5, CI 0.2-0.9) compared other diagnoses. These findings consistent both univariate- (Table 1). Figure cumulative hazard according diagnosis. Other 1) smoking 1.8, 1.0-3.3) holidays more than 12 weeks 4.7, 1.2-18.3). Additionally, higher activity 1.5, 1.0-2.3) (0.7, 0.6-0.8). co-treated methotrexate 0.4, thiopurines 0.3, 0.1-0.8), having increments 0.3-0.8), reduced immunogenicity. 1. Risk Results from regression Univariate Multivariate (Adjusted gender) OR 2.2** [1.3,3.8] 2.1* [1.1,3.9] 0.4** [0.2,0.8] 0.5* [0.2,0.9] Methotrexate 1.1 [0.7,1.9] 0.4* Thiopurine 0.3* [0.1,0.9] [0.1,0.8] Current former 1.8* [1.0,3.3] Mean 0.7*** [0.6,0.8] >12 between infusions 4.5* [1.3,16.0] 4.7* [1.2,18.3] increment [0.3,0.9] [0.3,0.8] DAS28 PsA) 1.5* [1.0,2.1] [1.0,2.3] ESR 1.1*** [1.0,1.1] CRP 1.1** * p<0.05, ** p<0.01, *** p<0.001 Only <0.05 are shown. Non-significant include dose. Conclusion: This study identified smoking, high monotherapy low Of particular interest, we found that significantly diseases. Whether novel finding reflects different underlying mechanisms fact receive not known needs be explored. References: [1]Thomas SS et al. BioDrugs 2015;29(4):241-58 Syversen SW Trials 2020 6;21(1):13 Disclosure Interests: Marthe Kirksæther Brun: None declared, Guro Løvik Goll Speakers bureau: Pfizer, AbbVie, Boehringer Ingelheim, Roche, Orion pharma, Sandoz Novartis, Kristin Kaasen Jørgensen Celltrion, AOP Orphan Pharmaceuticals Norgine, Joe Sexton: Johanna Elin Gehin Øystein Sandanger: Inge Olsen: Rolf Anton Klaasen: David J Warren: Cato Mørk Novartis Norge AS, LEO Pharma ACO Hud Cellgene Abbvie, Galderma Nordic UCB, Tore K. Kvien TAmgen, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sanofi, Consultant of: Amgen, Biogen, Eli Lilly, Gilead, Mylan, Grant/research support from: Research funding Diakonhjemmet Hospital BMS, MSD, Pfizer Jørgen Jahnsen: Nils Bolstad Roche Janssen, Espen Haavardsholm Celgene, Eli-Lilly Silje Watterdal Thermo Fisher.