Toggle Main Menu Toggle Search

Open Access padlockePrints

Clinical Utility of Random Anti-Tumor Necrosis Factor Drug-Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Lookup NU author(s): Professor John IsaacsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Objective. To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.Methods. A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.Results. Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody-positive patients received lower median dosages of methotrexate compared with antidrug antibody-negative patients (15 mg/week versus 20 mg/week; P = 0.01)and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of >= 30 kg/m(2) and poor adherence were associated with lower drug levels.Conclusion. Pharmacologic testing in anti-tumor necrosis factor-treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months.

Publication metadata

Author(s): Jani M, Chinoy H, Warren RB, Griffiths CEM, Plant D, Fu B, Morgan AW, Wilson AG, Isaacs JD, Hyrich KL, Barton A, Biology Rheumatoid Arthrit Genetic

Publication type: Article

Publication status: Published

Journal: Arthritis & Rheumatology

Year: 2015

Volume: 67

Issue: 8

Pages: 2011-2019

Print publication date: 01/08/2015

Online publication date: 28/07/2015

Acceptance date: 21/04/2015

Date deposited: 23/06/2016

ISSN (print): 2326-5191

ISSN (electronic): 2326-5205

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/art.39169


Altmetrics provided by Altmetric


Funder referenceFunder name
NIHR Biomedical Research Unit Funding Scheme
NIHR Manchester Musculoskeletal Biomedical Research Unit
Medical Evaluation Unit
North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics
20380Arthritis Research UK
20385Arthritis Research UK
G1000417/94909Medical Research Council