Patients with severe rheumatoid arthritis (RA) disease may be treated with tumor necrosis factor (TNF)-α inhibitors. However, their efficacy is reduced by the presence of anti-drug antibodies. The objective of this HTA was to conduct a systematic review to investigate the effectiveness of using enzyme-linked immunosorbent assay (ELISA) tests (Promonitor, IDKmonitor, LISA-TRACKER, RIDASCREEN, MabTrack, and Sanquin Diagnostic Services) to measure levels of the drug and anti-drug antibodies for monitoring response to TNF-α inhibitors in patients with RA.

A range of bibliographic databases including MEDLINE, EMBASE and CENTRAL were searched from inception to November 2018. Studies were eligible for inclusion if they investigated ELISA tests in RA patients receiving treatment with a TNF-α inhibitor who had achieved the treatment target (remission or low disease activity [LDA]) or experienced a primary or a secondary non-response. The tests must compare with standard care where treatment decisions are based on clinical judgements and monitoring using a composite score such as the disease activity score 28 joints (DAS28). Risk of bias was assessed using the Cochrane (ROBINS-1) tool for non-randomized studies.

Two studies were included. One non-randomized controlled trial (non-RCT) compared standard care with therapeutic drug monitoring using Promonitor test kits in RA patients in remission/LDA receiving adalimumab, and a historically controlled study investigated Sanquin ELISA kits. The non-RCT study showed that there was a non-significant reduction in the risk of flare in the intervention group compared with the control group. Patients’ health-related quality of life outcomes were higher in the intervention group at all visits compared with the control group. However, this study had serious limitations because analyses were not performed using an intention-to-treat approach. The historically controlled study did not provide valid evidence on whether ELISA-based monitoring is clinically effective.

There is only limited, poor evidence available. There are considerable uncertainties on the effectiveness of using ELISA tests for monitoring response to TNF-α inhibitors in RA. Further controlled trials are required.