SAT0211 Is there a potential for therapeutic drug monitoring of subcutaneous tocilizumab in patients with rheumatoid arthritis in daily practice?
Authors: Z. Layegh, M. J. L `Ami, C. Bastida, A. D. Huitema, C. Krieckaert, M. T. Nurmohamed, T. Rispens, G. Wolbink
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Tocilizumab (TCZ), is a humanized antibody that competitively inhibits membrane-bound and soluble IL-6 receptors. Subcutaneous (sc) TCZ might be a potential candidate for therapeutic drug monitoring (TDM) since a high variability in serum concentrations has been reported. Considering that TCZ concentrations above 1 µg/mL have been claimed to be sufficient for normalizing CRP production (1), there might be an overexposure in a substantial proportion of patients. We expect that patients can at least reduce to a dose aiming for a trough concentration of 5 µg/mL. Insights in serum concentrations of sc TCZ with clinical efficacy are lacking, but are necessary to reduce overexposure, potential dose-dependent adverse effects and at the same time reduce costs. <h3>Objectives:</h3> To describe TCZ trough serum concentrations in patients with rheumatoid arthritis (RA) treated with sc TCZ. <h3>Methods:</h3> Prospective study with consecutive RA patients starting treatment with sc TCZ between June 2015 to October 2017 who had previously failed treatment with at least two DMARDs, including MTX. TCZ was administered at a dose of 162 mg every week and patients were followed for 28 weeks. The study was conducted at the Amsterdam Rheumatology and Immunology Center | Reade. Serum trough samples were collected at baseline and at 4, 16, 28 weeks thereafter. An enzyme-linked immunosorbent assay (ELISA) was used for TCZ measurement. To analyze the concentration variability among patients at 28 weeks, a last observation carried forward approach was used. <h3>Results:</h3> In total, 26 patients were included in the study and 94 TCZ serum concentrations were measured. Median and interquartile range (IQR) of the follow-up period was 28 (16-28) weeks and 54% of the patients accomplished week 28. Drug concentrations ranged from 0.2 to 63 µg/mL, with an overall median (IQR) of 26,0 (10,5-42,0) µg/mL. In the majority of patients, TCZ concentrations stabilized after 4 weeks of treatment. Variability in drug concentrations at 28 weeks is shown in figure 1. Median (IQR) TCZ serum concentrations at 28 weeks was 24,0 (6.4-43,0) µg/mL, 92% of the patients achieved a concentration above 1 µg/mL and 88% had a concentration &gt; 5 µg/mL. <h3>Conclusions:</h3> The Interindividual variability among patients on sc TCZ is remarkably high. The majority of the patients achieved serum concentrations far above 5 µg/mL, suggesting overexposure in those patients. Therefore, TDM might be useful to optimize treatment, reduce (potential) side effects and achieve cost-effectiveness. <h3>Reference</h3> [1]Br J. Clin Phamacol2017May;83(5):962–975. <h3>Disclosure of Interest:</h3> Z. Layegh: None declared, M. L `Ami: None declared, C. Bastida: None declared, A. Huitema: None declared, C. Krieckaert Speakers bureau: Pfizer, M. Nurmohamed Grant/research support from: Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Eli Lilly, Sanofi, and Celgene, Speakers bureau: Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Eli Lilly, Sanofi, and Celgene, T. Rispens Grant/research support from: Pfizer, Speakers bureau: Pfizer, UCB, AbbVie, Biogen, BMS, G. Wolbink Grant/research support from: Pfizer, Speakers bureau: Abbvie, UCB, BMS, Pfizer, Biogen