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Clinical utility of random anti-TNF drug level testing and measurement of anti-drug antibodies on long-term treatment response in rheumatoid arthritis

Significance Statement

Clinicians at University of Manchester examined 311 patients with rheumatoid arthritis. By measuring anti-TNF  level in the blood and anti-drug antibodies levels they concluded that it may be possible to predict early which rheumatoid arthritis (RA) patients will fail to respond to adalimumab given to treat them. These findings could help better manage patients’ symptoms. Although these tests are can be easily performed in a hospital setting, next step would be to explore whether such test is cost-effective in clinical practice.

Clinical utility of random anti-TNF drug level testing and measurement of anti-drug antibodies

 

Journal Reference

Jani M, Chinoy H, Warren RB, Em Griffiths C, Plant D, Fu B, Morgan AW, Wilson AG, Isaacs JD, Hyrich KL, Barton A;BRAGGSS. Arthritis Rheumatol. 2015 Jun 24. doi: 10.1002/art.39169.

Show Affiliations

Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom

Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester. National Institute of Health Research Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester Academic Health Science, Manchester, United Kingdom

The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom

The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom

Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester. National Institute of Health Research Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester Academic Health Science, Manchester, United Kingdom

Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, National Institute of Health Research Leeds Musculoskeletal Biomedical Research Unit, Leeds, United Kingdom

Academic Unit of Rheumatology, Department of Infection and Immunity, University of Sheffield Medical School, Sheffield, United Kingdom

Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University and National Institute of Health Research Newcastle Biomedical Research Centre, Newcastle upon Tyne, United Kingdom

10 Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester, United Kingdom

11 Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester. National Institute of Health Research Manchester Musculoskeletal Biomedical Research Unit, University of Manchester, Manchester Academic Health Science, Manchester, United Kingdom

Abstract

Objective (1) To investigate whether anti-drug antibodies (ADAb) and/or non-trough drug levels predict long term treatment response in a large rheumatoid arthritis (RA) cohort treated with adalimumab or etanercept; (2) To identify factors influencing ADAbs and drug levels to optimise future treatment decisions. Methods 331 patients were selected from an observational prospective cohort (n=160 adalimumab; n=171 etanercept). ADAb levels were measured using radioimmunoassay and drug levels measured using ELISA in 835 serial serum samples 3/6/12 months post-therapy initiation. The association and predictive value of ADAb and/or non-trough drug levels on treatment response (ΔDAS28 score), was evaluated. Results ADAbs were detected in 24.8% (31/125) patients on adalimumab and no patients on etanercept completing 12-month follow up. At 3 months, ADAb formation and low adalimumab levels were significant predictors of 12 month no EULAR response (area under curve 0.71, 95% confidence intervals [CI] 0.57-0.85). ADAb-positive patients received lower median methotrexate doses (15 vs. 20mg/wk, p=0.01) and had longer disease duration (14.0 vs. 7 years, p=0.03). Adalimumab levels best predicted ΔDAS28 at 12 months after adjustment (regression coefficient 0.060 [CI: 0.015-0.10] p=0.009). Etanercept levels were associated with 12 month EULAR response (regression coefficient 0.088 [CI 0.019 -0.16] p=0.012), however this was not significant after adjustment. BMI ≥ 30 and poor adherence were associated with lower drug levels. Conclusion Pharmacological testing in anti-TNF initiated patients is clinically useful even in the absence of trough levels. At 3 months, ADAbs and low adalimumab drug levels are significant predictors of lack of 12 month EULAR response. This article is protected by copyright. All rights reserved.

© 2015, American College of Rheumatology.

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