Title: Promonitor for therapeutic drug monitoring in rheumatoid arthritis
Funder: Department of Health and Social Care

Abstract: The purpose of this work is to provide NICE with the most up to date evidence on the effectiveness and cost-effectiveness of alternative testing and monitoring approaches using ELISAs for assessing TNF-a inhibitor levels and antibodies to TNF-a inhibitors levels in people with RA in the UK. The ‘decision problem’ is in fact potentially (i.e. relevant empirical data allowing) a number of discrete decision problems, because: ? There are 15 alternative patient target populations for whom different testing/monitoring strategies might be deemed cost-effective (this is because there are 5 different TNF-a inhibitors, multiplied by the 3 specific circumstances in which such circulating drug and drug anti-body testing is deemed to be clinically appropriate: primary non-response, secondary non-response, remission/low disease activity ? Also, depending on which TNF-a inhibitor a patient is taking, there are between 2 and 6 alternative testing kits/diagnostic services, plus the alternative of current clinical judgement with use of composite treatment response scores (DAS28,EULAR) If data permit, the treatment effect data will be pooled and an average effect will be estimated. NB. Empirical data permitting, other potential variations in the mode of provision of treatment monitoring (e.g. concurrent vs reflex testing on antibodies; free vs total drug/antibody testing) might be explored through supplementary scenario analyses, rather than as part of the main reference case analyses.

Lay abstract: Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune disease that typically affects synovial joints (such as those in the hands and feet), causing swelling, stiffness, pain and progressive irreversible joint destruction. Disease can also occur outside the joints, affecting other organs, including the lungs, heart and eyes. In RA, too much of a protein called tumour necrosis factor (TNF)-a is produced in the body, causing inflammation, pain and damage to the bones and joints, and is manifested with increasing disability and reduced quality of life. Physicians commonly prescribe different TNF-a inhibitors to treat severe RA. The TNF-a inhibitors block the action of TNF-a and, therefore, reduce inflammation. Although these drugs can help many people with RA, there are some people whose diseasedoes not respond to treatment (primary non-responders), and many people whose disease first responds to treatment find that their disease stops responding over time (secondary non-responders). The loss of response may be caused by a number of factors including the presence of antibodies to the drugs, and fluctuations in circulating drug levels. Anti-drug antibodies can be elicited by the drugs during therapy as a response by the human immune system to these medications. These anti-drug antibodies have been shown to reduce drug levels. ELISA tests can be used for measuring the drug levels and anti-drug antibody levels in serum/plasma of patients treated with TNF-a inhibitors. It is expected that therapeutic monitoring of TNF-a inhibitors using ELISA tests might be useful in the treatment of RA for primary and secondary loss of response to therapy and in the optimisation of dosages for those who are already responding. The ELISA tests will be conducted in addition to current clinical practice in the UK, i.e. clinical assessment and monitoring using a composite score such as the Disease Activity Score (DAS) 28. Therapeutic drug monitoring of TNF-a inhibitors for RA is not routine in most clinical practices in the UK, or at least does not use biochemical assays to quantify the level of drug or antibodies to the drug in a patient’s body. There are neither gold standards nor guidelines available to monitor these drugs. This technology assessment will identify and synthesise research evidence on outcomes and costs of six alternative ELISA kits/processes: - Promonitor test (Grifols - Progenika) - IDKmonitor enzyme-linked immunosorbent assay (ELISA) kits (Immundiagnostik/BioHit Healthcare) - LISA-TRACKER ELISA kits (Theradiag) - RIDASCREEN (R-Biopharm) - MabTrack ELISA kits (Sanquin) and - Sanquin Diagnostic Services (testing service using validated ELISAs) for assessing response to anti-TNF treatments, and their clinical and cost effectiveness compared to standard-of-care when treatment decisions are based on clinical judgement and regular monitoring using a composite score such as DAS28. The study will be conducted by Peninsula Technology Assessment Group (PenTAG).

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFLAMMATORY AND IMMUNE SYSTEM