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FRI0185 A systematic review and bivariate meta-analysis of studies that measured adalimumab drug levels by elisa to detect treatment response in rheumatoid arthritis
  1. S Gavan1,2,
  2. K Payne1,
  3. A Barton2,3
  1. 1Manchester Centre for Health Economics, The University of Manchester
  2. 2National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit at Central Manchester University Hospitals NHS Foundation Trust
  3. 3Centre for Musculoskeletal Research, The University of Manchester, Manchester, United Kingdom

Abstract

Background Previous research has demonstrated an association between circulating drug levels and treatment response in patients with rheumatoid arthritis that received the anti-TNF therapy adalimumab. Commercial ELISA assays are now available for use in routine practice to monitor anti-TNF drug levels at regular intervals. However, the ability to detect treatment response by measuring adalimumab drug levels using an ELISA is uncertain.

Objectives The objectives of this research were to identify and synthesise all published studies that investigated the accuracy of measuring adalimumab drug levels by ELISA to detect treatment response in patients with rheumatoid arthritis.

Methods A systematic review identified all published studies that performed a receiver operating characteristic (ROC) analysis to detect treatment response in patients with rheumatoid arthritis by measuring adalimumab drug levels using an ELISA. Medline and Embase were searched electronically from inception to August 2016. Two researchers independently identified studies for the review using a pre-defined inclusion criteria. Assay results were classified as positive if adalimumab drug levels exceeded the cut-point reported in each study. Study design characteristics, sample characteristics, and test outcomes from 2x2 tables (true-positive; false-positive; true-negative; false-negative) were extracted from each study. The quality of each study was assessed using the QUADAS-2. A hierarchical bivariate meta-analysis synthesised the findings of the ROC analyses to account for between-study heterogeneity and correlation between assay sensitivity and specificity.

Results The search strategy identified 4,006 abstracts and four studies met the inclusion criteria of the systematic review. Patients received 40mg adalimumab every two weeks in all studies. Studies varied in their design and sample characteristics, but had low risk of bias and low concern of applicability to the research objective. The hierarchical bivariate meta-analysis estimated that measuring high adalimumab drug levels by ELISA detected treatment response with an average sensitivity of 0.95 (95% CI: 0.85–0.98) and specificity of 0.68 (95% CI: 0.28–0.92).

Conclusions Measuring high adalimumab drug levels by ELISA in patients with rheumatoid arthritis appeared to be predictive of treatment response. However, the measurement of low adalimumab drug levels was less predictive of no response to treatment. In practice, test accuracy may be improved by measuring anti-drug antibodies alongside adalimumab drug levels. Given the imperfect accuracy of ELISA assays, the relative cost-effectiveness of drug level monitoring should be evaluated before being recommended for use in routine practice.

Acknowledgements SG acknowledges support from a National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit Ph.D studentship. We also acknowledge support from MATURA, a stratified medicine initiative funded jointly by the Medical Research Council and Arthritis Research UK (MR/K015346/1).

Disclosure of Interest None declared

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