RIDASCREEN tests for monitoring infliximab in inflammatory bowel disease

Table 1 Comparative specifications of the RIDASCREEN tests

Both tests need additional equipment to be used, specifically: precision micropipettes and standard pipettes, a microplate washer or multichannel pipette, a 37°C incubator and a spectrophotometer (450 nm) or microplate reader (for manual mode). This equipment is readily available in most pathology laboratories. The manufacturer can supply its own microplate reader, the Dynex DS2, if needed.

For each sample, the concentration of free infliximab or antibodies against infliximab is calculated using the 6 standards. Laboratories with semi-automated ELISA platforms will have the software to do this calculation automatically. However, the evaluation software RIDASOFT Win.net is available for free from the company if needed.

R-Biopharm has recently developed RIDA QUICK IFX Monitoring, which is a rapid lateral flow test to quantify infliximab trough levels within 20 minutes. The company also has a number of other ELISAs including RIDASCREEN ADM Monitoring for the quantitative determination of another TNF‑alpha inhibitor, adalimumab. However, these tests are beyond the scope of this briefing.

Innovations

The tests are designed to guide further treatment using information on how a person's body processes and responds to infliximab, which is known to vary significantly between people. This may be more precise than current management options such as empiric dose intensification, switching agents or immunomodulation.

RIDASCREEN tests are the commercially available products which were described in the NICE diagnostics guidance on therapeutic monitoring of TNF-alpha inhibitors in Crohn's disease as the Leuven in-house ELISA.

Current NHS pathway or current care pathway

The current diagnostic and care pathways for Crohn's disease are described in the NICE diagnostics guidance on therapeutic monitoring of TNF-alpha inhibitors in Crohn's disease. NICE technology appraisal guidance on infliximab, adalimumab and golimumab describes the current management pathway for ulcerative colitis.

NICE recommends initial induction treatment with infliximab of intravenous infusion at 0, 2 and 6 weeks. No further treatment should be offered if the disease does not respond to this induction treatment. The specialist commentators who contributed to this briefing indicated that current practice would include measurement of infliximab levels in people whose disease has not responded at this point, using a test such as RIDASCREEN IFX Monitoring.

People whose disease responds to the induction treatment will progress to maintenance treatment. If their disease stops responding over time, treatment decisions are based on 'trial and error'. This includes shortening the interval between dosing, increasing the dose, switching to a different drug treatment and immunomodulation.

NICE diagnostics guidance on therapeutic monitoring of TNF-alpha inhibitors in Crohn's disease considers the use of these tests during the maintenance phase of treatment, but concludes that there is insufficient evidence to recommend their routine use in the NHS.

The RIDASCREEN Anti‑IFX Antibodies test cannot measure antibodies against infliximab in samples that have a high level of infliximab: it can only be done if there is less than 1 microgram/ml in the sample. Therefore, a reflex testing strategy should be used. The RIDASCREEN IFX Monitoring test is done first; if the drug is undetectable, the Anti‑IFX Antibodies test is used.

NICE is aware of the following CE-marked devices that appear to fulfil a similar function to the RIDASCREEN IFX Monitoring and Anti‑IFX Antibodies tests:

Population, setting and intended user

The RIDASCREEN tests would be used in addition to existing investigations to guide treatment of IBD with infliximab. Treatment with infliximab is managed by clinicians with experience of tumour necrosis factor‑alpha (TNF-alpha) inhibitors and of managing IBD, such as gastroenterologists.

The tests would be done after the induction treatment and during maintenance treatment, before infusion with infliximab, in a hospital setting. They would be done in clinical laboratories and run by qualified laboratory staff with appropriate training on the test and system. The laboratory staff should work closely with the treating or referring clinician, in a network, to ensure appropriate use of the tests and interpretation of the results.

Costs

Resource consequences

In centres where therapeutic drug monitoring of infliximab is not current practice, the use of RIDASCREEN IFX Monitoring and Anti‑IFX Antibodies tests would represent additional acquisition costs. However, these costs could be offset by savings from drug therapy optimisation and improved disease management.

The per-patient costs of the RIDASCREEN tests are similar to those presented in the NICE diagnostics guidance on therapeutic monitoring of TNF-alpha inhibitors in Crohn's disease. Therefore, for centres that already offer infliximab testing using one of these methods, the RIDASCREEN tests would be unlikely to represent an additional cost.

The economic models described in the NICE diagnostics guidance show that reflex testing strategies are less costly but less effective than standard care. However, the losses reported by the economic model were uncertain because of the difficulties in measuring quality of life in these populations. These results are likely to be generalisable to the RIDASCREEN tests.