Clinical and technical evidence
A literature search was carried out for this briefing in accordance with the interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting firstname.lastname@example.org.
The literature search identified 10 studies that reported on the use of the RIDASCREEN tests for monitoring infliximab in inflammatory bowel disease (IBD). These include studies reporting on the earlier, pre-commercialised versions of the tests (Leuven in-house enzyme-linked immunosorbent assay [ELISA] method), because they were considered comparable to the current versions of the test. Studies reporting on these tests under their apDia branding were also included.
Five of these studies (table 3; n=587 serum samples in total) reported relevant clinical outcomes. These comprise 1 prospective observational study (Van Stappen et al. 2016) and 4 studies that had relevant test comparisons which reported concordance data (Marini et al. 2017, Lee et al. 2016, Malickova et al. 2016, Schmitz et al. 2015).
This briefing excludes 1 randomised controlled trial (TAXIT; Vande Casteele et al. 2015) and 1 test comparison study (Vande Casteele et al. 2012) from full review, because they are summarised in the NICE diagnostics guidance on therapeutic monitoring of TNF-alpha inhibitors in Crohn's disease. Three bench-test studies (Van Stappen et al. 2015a, Van Stappen et al. 2015b, Gils et al. 2016) were also excluded because they did not include clinical outcomes.
Table 3 summarises the clinical evidence as well as its strengths and limitations.
Only 1 relevant additional study (Van Stappen et al. 2016) was identified since the publication of the NICE diagnostics guidance on therapeutic monitoring of TNF-alpha inhibitors in Crohn's disease in February 2016. This study included clinical outcome data on the use of a pre-commercialised version of the RIDASCREEN Anti‑IFX Antibodies test. However, clinical outcome data were limited because it was not the primary outcome of the study. No information was reported on how therapeutic drug monitoring had helped with the management of symptoms.
In the absence of a gold-standard reference method for therapeutic drug monitoring of infliximab, there is limited evidence on the accuracy of the RIDASCREEN tests. Therefore, the evidence base is largely focused on correlation studies with other ELISAs for therapeutic drug monitoring of infliximab.
Only the Lee et al. (2016) and Schmitz et al. (2015) studies clearly stated which platforms were used for analysis, or whether the analysis was automated or manual.
The evidence base would be improved by prospective studies evaluating the clinical outcomes associated with using the tests.
Two of the specialist commentators highlighted an analytical evaluation study of the RIDASCREEN IFX Monitoring test. This was presented as a poster at the British Society of Gastroenterology Conference in 2016, and is due to be published as a paper in 2017.
Comments on these technologies were invited from clinical experts working in the field and relevant patient organisations. The comments received are individual opinions and do not represent NICE's view.
All 4 specialist commentators were familiar with the RIDASCREEN tests and 2 had used them for research purposes. Three specialist commentators routinely use therapeutic drug monitoring, but none uses the RIDASCREEN tests.
Three specialist commentators considered the RIDASCREEN tests to have little innovation because similar technologies already exist and are readily available. One added that RIDASCREEN is only a minor variation on existing tests. The fourth commentator highlighted that the University of Leuven uses the RIDASCREEN tests, and this is one of the leading and reputable centres in this field.
One commentator considered that ELISA technologies will likely be superseded in the near future by fully automated immunoassays, which offer higher throughput and efficiencies of scale.
Two specialist commentators considered that therapeutic drug monitoring is widely recognised as best practice in managing IBD, but that this isn't currently reflected in national guidelines. One added that 3 centres in the UK already offering routine testing using tests other than RIDASCREEN.
Three commentators indicated that the RIDASCREEN tests allow a personalised approach to drug optimisation, which is better for patients than empirical dose escalation. One added that this is particularly useful in patients whose disease doesn't respond (primary non-response) or stops responding (secondary loss of response). Additionally, 2 commentators considered that the tests reduce exposure to unnecessary, potentially harmful drugs in certain patients.
One specialist commentator described an analysis in their practice which demonstrated that in most people with secondary loss of response, the amount of infliximab in the blood had reached the therapeutic level. This means that the lack of response was not caused by a shortage of infliximab, so an increased dose wouldn't help.
One commentator added that patients who test positive for antibodies against infliximab are at an increased risk of infusion reactions. They felt that therapeutic drug monitoring may help to achieve a better response to infliximab treatment. This could help eliminate disease-related symptoms and improve quality of life with as few side effects as possible.
Three specialist commentators considered that no changes in facilities or infrastructure would be needed because similar technologies are already used in the NHS. One commentator disagreed, and felt that any centre choosing to adopt the RIDASCREEN tests would need some infrastructural changes before implementation. Additional training may also be needed for any extra equipment (such as the Dynex DS2).
Another commentator highlighted that interpreting the results of the tests needs considerable expertise and understanding of their limitations, and appropriate network facilities and software would be needed to transfer patient results.
All 4 specialist commentators considered that the RIDASCREEN tests could lead to cost savings for the NHS. Three added that cost analyses should take the cheaper costs of biosimilars into account.
One commentator described that from their experience, the test cost was negligible compared with the annual cost of infliximab per patient. Costs savings can be achieved by dose de-escalation, drug optimisation and better outcomes for patients. They considered that using the tests may also reduce future hospital admissions.
One specialist commentator explained that, for the RIDASCREEN Anti‑IFX Antibodies test kit, they run singlicate patient samples but at 2 different dilutions (1:25 and 1:200), so the maximum number of patient samples per plate in this instance is 40. Another commentator advised that sample dilutions for infliximab measurement may later affect the number of samples that will need repeat testing for absolute values.
One commentator highlighted that routine use of the RIDASCREEN tests is subject to the same limitations noted in the NICE diagnostics guidance on therapeutic monitoring of TNF-alpha inhibitors in Crohn's disease, and further research is needed to address this issue.
Two commentators highlighted that a full analytical verification of the RIDASCREEN tests on existing microplate readers would be needed before offering a clinical service. One added that laboratories using an automated or semi-automated ELISA platform would need to ensure acceptability of the in-built software, in use and implement sufficient quality control procedures and validation criteria for ongoing quality assurance. One commentator further advised that manual methods would not be recommended for routine services.