THU0243 A Concentration-Effect Curve of Adalimumab in Ankylosing Spondylitis Patients; Does it Exist or Not?
Authors: A. Marsman, E. Kneepkens, J. Ruwaard, J. Cheng-Chung Wei, T. Rispens, M. Nurmohamed, C. van Denderen, I. van der Horst-Bruinsma, G. Wolbink
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> To date, it is not common practice yet to measure drug levels of TNF inhibitors. In rheumatoid arthritis (RA) and psoriatic arthritis (PsA) the relation between adalimumab trough level and clinical response has been investigated [1,2]. In ankylosing spondylitis (AS) there is a lack of knowledge about the pharmacokinetics of adalimumab. Pharmacokinetics might be different in AS as the underlying disease mechanisms and patient characteristics in AS differ from RA and PsA. <h3>Objectives</h3> To determine the concentration-effect curve in AS patients treated with adalimumab 40 mg every other week and to identify a therapeutic range for adalimumab concentrations after 24 weeks of treatment. <h3>Methods</h3> This prospective cohort study included 102 consecutive adalimumab-treated AS patients in the Netherlands and Taiwan. The relation between adalimumab trough level and clinical efficacy after 24 weeks of follow-up was determined in a concentration-effect curve, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Adalimumab concentrations were measured in serum, using an enzyme linked immunosorbent assay (ELISA). All patients were sorted from low to high adalimumab concentration. Each dot represents 12 patients (the last dot represents 6 patients) and corresponding mean adalimumab trough concentration and ΔBASDAI. <h3>Results</h3> Active disease defined as BASDAI ≥4 was present in 79% of patients at baseline. At 24 weeks of treatment 36% of patients showed a decrease of ≥2.0 in ΔBASDAI. A large variation in adalimumab concentration was seen, ranging from 0 to 40.9 mg/l (figure 1). Drug level in patients with elevated CRP at baseline tended to be lower. In the concentration-effect curve, no optimal therapeutic range for adalimumab concentration could be detected. Surprisingly, also patients with low or undetectable adalimumab in serum (n=11) showed response to therapy. <h3>Conclusions</h3> An optimal therapeutic range for adalimumab in AS using serum adalimumab trough level and ΔBASDAI could not be established in this cohort. An explanation for response to therapy despite undetectable adalimumab level at trough in a subset of patients might be due to sample timing. Possibly, some patients have adequate amounts of adalimumab in serum to effectively block the TNF pathway, following administration of the drug. As a consequence of the absence of an evident therapeutic range, future tapering studies can hypothetically be performed based on clinical parameters alone. Measurement of corresponding change in drug level is important for a better understanding of adalimumab pharmacokinetics and the minimum required drug level for maintaining low disease activity. This will also contribute to a better understanding of the potential role of therapeutic drug monitoring in this patient population. <h3>References</h3> Pouw MF et al. ARD 2013. Vogelzang EH et al. ARD 2014. <h3>Disclosure of Interest</h3> A. Marsman: None declared, E. Kneepkens Speakers bureau: Pfizer, J. Ruwaard: None declared, J. Cheng-Chung Wei: None declared, T. Rispens: None declared, M. Nurmohamed Consultant for: Abbott, Roche, Pfizer, MSD, UCB, SOBI and BMS., Speakers bureau: Abbott, Roche and Pfizer., C. van Denderen: None declared, I. van der Horst-Bruinsma: None declared, G. Wolbink Grant/research support from: Pfizer (paid to the institution)., Speakers bureau: Pfizer, Amgen, Abbvie, UCB and BMS.