Guidance
3 The diagnostic tests
3.1 The assessment compared 6 intervention tests (enzyme-linked immunosorbent assay [ELISA] tests: Promonitor, IDKmonitor, LISA‑TRACKER, RIDASCREEN, MabTrack, and in-house tests used by Sanquin Diagnostic Services) with 1 comparator (standard care). These ELISA tests are intended to be used for measuring the levels of tumour necrosis factor (TNF)‑alpha inhibitors and antibodies to TNF‑alpha inhibitors in the blood of people having TNF‑alpha inhibitor treatment for rheumatoid arthritis.
3.2 Single or duplicate ELISA tests may be done. Testing can be concurrent or reflex, and can include testing of free or total antibody levels:
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Concurrent testing: tests for TNF‑alpha inhibitor drug levels and antibodies to TNF‑alpha inhibitors are done at the same time.
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Reflex testing: the test for TNF‑alpha inhibitor drug levels is done first. If the drug is undetectable, testing for antibodies to the TNF‑alpha inhibitor would be done without a further request from the treating clinician. If TNF‑alpha inhibitor is present in the sample, then testing for antibodies would not be done.
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Testing of free antibody levels: the test measures the levels of antidrug antibodies that are unbound to drug.
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Testing of total antidrug antibody levels: the test measures levels of both unbound (free) antidrug antibodies and those bound to TNF‑alpha inhibitor.
The interventions
3.3 The ELISA tests are all similar and consist of strips of pre-coated microtitre plate (96 wells), reagents, buffers, standards or calibrators, and controls (see table 1). The tests are done either manually or on an automated ELISA processor in a laboratory.
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ELISA kits and tests relevant to this assessment |
Manufacturer and UK distributor |
|---|---|
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Promonitor; 8 CE-marked ELISA kits, 4 measuring the levels of circulating TNF‑alpha inhibitor (adalimumab, etanercept, infliximab or golimumab) and 4 measuring the levels of corresponding free antidrug antibodies. |
Proteomika, distributed by Grifols UK |
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IDKmonitor; 10 CE-marked ELISA kits, 4 measuring the levels of free TNF‑alpha inhibitor (adalimumab, etanercept, infliximab or golimumab), 4 measuring corresponding levels of free antidrug antibodies and 2 measuring the levels of total antidrug antibodies (against adalimumab or infliximab). |
Immundiagnostik, distributed by BioHit Healthcare Ltd |
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LISA-TRACKER; 10 CE-marked ELISA kits, 5 measuring the levels of free TNF‑alpha inhibitor (adalimumab, certolizumab pegol, etanercept, infliximab or golimumab) and 5 measuring the corresponding levels of free antidrug antibodies. LISA-TRACKER Duo kits are also available that include assays to measure the levels of both free antidrug antibodies and TNF‑alpha inhibitor. |
Theradiag, distributed by Cambridge Life Sciences Ltd |
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RIDASCREEN; 4 CE-marked ELISA kits, 2 measuring the levels of free TNF‑alpha inhibitor (adalimumab or infliximab) and 2 measuring the corresponding levels of free antidrug antibodies. They are commercial versions of the KU Leuven in-house ELISAs, and are marketed as apDia ELISA kits in Belgium, the Netherlands, and Luxembourg. |
R-Biopharm |
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MabTrack; 4 CE-marked ELISA kits; 2 measuring the levels of free TNF‑alpha inhibitor (adalimumab and infliximab) and 2 measuring the corresponding levels of free antidrug antibodies. They are commercial versions of the Sanquin in-house ELISAs. |
Sanquin |
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Sanquin Diagnostic Services ELISA tests. Validated ELISAs are available for adalimumab, infliximab, golimumab, etanercept and certolizumab and their corresponding antidrug antibodies. |
Test service provided by Sanquin Diagnostic Services, a laboratory in the Netherlands |
Abbreviations: ELISA, enzyme-linked immunosorbent assay; TNF, tumour necrosis factor.
The comparator
3.4 The comparator for this assessment is treatment decisions based on clinical judgement only, without measuring the levels of TNF‑alpha inhibitor or antibodies to TNF‑alpha inhibitor. Clinical judgement usually includes assessing disease activity, treatment response, functioning, quality of life, comorbidities, complications and the need for surgery.