AB0382 TROUGH VERSUS NON-TROUGH ADALIMUMAB DRUG LEVEL MEASUREMENTS

Abstract

Background Over the last years there has been an increasing interest for measuring drug levels to guide decision-making. Serum samples used for these measurements are often obtained prior to the next injection, at trough level. However, Jani et al. (2015) analyzed drug levels of randomly acquired serum samples from patients with rheumatoid arthritis (RA) treated with either etanercept or adalimumab and found a significant relationship with clinical disease activity. This indicates that random drug level measurements might also be useful (1). However, more aspects should be considered before deciding to use non-trough measurements. Objectives To assess the effect of non-trough measurements, compared to trough measurements, on serum drug level. Methods Patients with RA starting adalimumab treatment were included in this prospective observational cohort study, named the Reade Rheumatology Registry. Serum samples were obtained during every visit and these were analyzed for drug levels using a regular enzyme-linked immunosorbent assay (Sanquin, Amsterdam). The date of a patients’ last injection with adalimumab was documented. Samples were included in the analyses if the interval between the last injection and serum sampling did not exceed 28 days, as in general patients do not have such long dosing-intervals. The analysis was performed using Spearman correlation. Results In total, 121 RA patients were included in this study. The median follow-up period of these patients was 156 (interquartile range (IQR) 78-247) weeks. Drug level measurements were performed in all serum samples that were obtained. In total, 310 measurements were included in the analyses, as from this subset the date of the previous injection with adalimumab was documented. The median drug level during adalimumab treatment was 6.6 (IQR 4.2-9.8) µg/ml, and the median number of days between the previous injection of adalimumab and serum sampling was 8 (5-13). The latter was divided into quartiles and plotted against drug level (Figure 1). The first quartile (median 2 (IQR 1-3) days) had a median drug level of 8.0 (4.7-11.0) µg/ml, the second quartile (7 (6-8) days) of 6.9 (5.4-10.0) µg/ml, the third quartile (11 (10-12) days) of 6.1 (3.4-9.5) µg/ml, and the fourth quartile (14 (13-14) days) of 5.7 (3.1-8.5) µg/ml. A weak association was found between the number of days between the previous injection of adalimumab and serum sampling and adalimumab drug level (Spearman’s ρ: -0.182, p=0.001). Conclusion The growing interest to apply therapeutic drug monitoring (TDM) within the field of rheumatology forces us to discuss which measurements, trough or non-trough, are most informative. We found a correlation between the number of days between the previous injection of adalimumab and serum sampling, and adalimumab drug level. This might suggest that the timing of serum sampling affects the measured drug level, which could have consequences for treatment decisions based on these drug levels.