OP0112 Therapeutic drug monitoring to optimise switching between biologic agents in rheumatoid arthritis
Authors: M.J. l’Ami, J. Ruwaard, C.L. Krieckaert, M.T. Nurmohamed, T. Rispens, G. Wolbink
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Many patients with rheumatoid arthritis (RA) are treated with tumour necrosis factor inhibitors (TNFi). It is, however, unclear whether to switch to a second TNFi or to another mode of action drug in case of non-response. The detection of anti-drug antibodies (ADAs) have shown to be related to the response rate of a second TNFi.<sup>1</sup> The detection of ADAs is, however, to a large extent dependent of the type of assay used and, moreover, the efficacy of the drug is determined by the pharmacokinetics. Therefore, it more logical to use drug levels in daily clinical practice. <h3>Objectives</h3> To investigate whether serum drug concentration of patient's first TNFi, adalimumab, was related to the effectiveness of a second TNFi, etanercept. <h3>Methods</h3> Consecutive patients with RA treated with etanercept were followed in the Reade Rheumatology Registry, an observational cohort (NTR no.6868). Patients who were treated with adalimumab 40 mg every other week previously (switchers; n=69) were compared to patients starting etanercept without prior biologic agents (biologic-naïve; n=380). Patients received etanercept 50 mg weekly or 25 mg twice a week. Switchers were divided into three groups; respectively low- (&lt;0.5 µg/mL), intermediate- (0.5 and 5.0 µg/mL) and high- (&gt;5.0 µg/mL) adalimumab concentration. The last available serum sample before adalimumab discontinuation was assessed for adalimumab concentrations by enzyme linked immunosorbent assay (ELISA). ADAs were measured using the antigen binding test (ABT). Clinical endpoints were percentage of patients achieving European League Against Rheumatism (EULAR) good or moderate response and the Simplified Disease Activity Index remission criteria (SDAI &lt;3.3) after 52 weeks. <h3>Results</h3> Median (IQR) adalimumab concentration of the switcher-groups with low (n=18), intermediate (n=18) and high concentrations (n=27) were, respectively 0.0 µg/mL (0.0–0.05), 2.5 µg/mL (1.5–4.3) and 7.4 µg/mL (6.0–11.8). ADAs were detected in, respectively 16 patients (89%), 6 patients (33%) and 3 patients (11%). Response rate of switchers with low adalimumab concentrations was comparable to biological-naive patients, whereas switchers with intermediate and high concentrations responded worse regarding EULAR response criteria (respectively 74%, 72%, 50% and 52%; figure 1A) and SDAI remission (respectively 27%, 27%, 6%, 11%; figure 1B). <h3>Conclusions</h3> For the first time, we showed that the response rate of switchers with low adalimumab concentrations was comparable to biological-naive patients, whereas switchers with intermediate and high concentrations responded worse. Therefore, drug concentration assessment may optimise switching, as it helps to identify those patients that may benefit from a second TNFi. <h3>Reference</h3> [1] Jamnitski A, Bartelds GM, Nurmohamed MT, et al. The presence or absence of antibodies to infliximab or adalimumab determines the outcome of switching to etanercept. Ann Rheum Dis2011;70:284–288. <h3>Disclosure of Interest</h3> M. l'Ami: None declared, J. Ruwaard: 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: Genmab, Speakers bureau: Pfizer, AbbVie and Regeneron, G. Wolbink Grant/research support from: Pfizer, Speakers bureau: Pfizer, UCB, AbbVie, Biogen, BMS