Original Title: MSAC application 1582

Authors' objectives: To assess the safety, effectiveness and cost-effectiveness of aquaporin 4 antibody (AQP4-Ab) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) testing for the diagnosis of neuromyelitis optica spectrum disorders (NMOSD), for consideration for listing on the Australian Pharmaceutical Benefits Scheme. The presence of AQP4-Ab and MOG-Ab allows earlier diagnosis and treatment of NMOSD, where the symptoms overlap with other autoimmune disorders of the central nervous system. AQP4-Ab testing was previously performed and rebated under a generic item number.

Authors' results and conclusions: Safety: no studies were identified that directly assessed the safety of antibody testing in people suspected of NMOSD. Testing of a blood sample is unlikely to result in adverse effects. Adverse events are associated with treatment of NMOSD, but event rates were not reliable. Effectiveness: from the linked evidence approach, diagnostic performance was limited to the type of assay used, and showed that three types of cell-based assays (live and fixed, and fluorescence-activating cell sorting) agreed with eachother. The studies were unable to show if the assays accurately detect AQP4-Ab. Diagnostic accuracy data was complicated by issues associated with the intervention and clinical reference standard. Only diagnostic yield data was available, with published literature reporting yield of between 34% and 43%. However Australian clinical practice data reported a much lower yield (between 2.9% and 5.4%); this likely reflects a much broader testing population than that tested in the published studies. Supportive prognostic data were included in the linked evidence. Evidence showed that the presence of AQP4-Ab indicates the risk of clinically significantly worse outcomes in those suspected of NMOSD. Data for MOG-Ab were similar although less consistent. Change in management evidence showed that patients are diagnosed earlier in the course of their disease when antibody testing is included in the diagnostic pathway. The association between AQP4-Ab testing and earlier diagnosis was strong, but confidence in the results was reduced by the risk of bias in the observational study designs. No evidence was identified for MOG-Ab testing. The outcomes for patients suspected of NMOSD can be summarised as: True positives: Patients are likely to benefit from earlier diagnosis and treatment. Earlier treatment can be effective in reducing disability and relapse rate. There is a risk of serious side effects from treatments. True negatives: Patients are likely to undergo further testing to correctly classify their inflammatory demyelinating disease. False positives: Unlikely to be recognised in a clinical setting. If a false positive result is suspected (for example in a control test) a retest could be considered. False negatives: Patients are likely to be treated as though they are suspected of NMOSD. Effective treatment may be delayed as a diagnosis may not be definitive until further symptoms occur. Delayed treatment may result in worse health outcomes. Alternatively patients may be treated as though they have MS and receive ineffective treatment. Overall: relative to diagnosis of NMOSD without AQP4-Ab testing, diagnosis with testing and associated treatments has non-inferior safety and superior effectiveness. Diagnosis of NMOSD with MOG-Ab testing, relative to diagnosis of NMOSD without MOG-Ab testing, has uncertain safety and uncertain effectiveness. Retesting or monitoring of NMOSD with AQP4-AB or MOG-Ab testing, relative to retesting or monitoring without the testing, has uncertain safety and uncertain effectiveness. Economic analysis: The analysis found that AQP4-Ab testing resulted in a cost saving and QALY gain, compared with no testing. Sensitivity analysis showed that the AQP4-Ab testing strategy remained less costly and more effective for all the model inputs assessed. The financial implications of listing the test were associated with the growth rate in the number of tests.

Authors' methods: A systematic literature review was undertaken. No studies reporting the direct effectiveness or safety of antibody testing were identified. A linked evidence approach was used and included k=2 studies assessing analytical validity, k=23 studies assessing clinical validity including diagnostic accuracy, diagnostic yield and prognostic information, and k=22 studies assessed therapeutic efficacy. A cost-utility analysis was performed for the economic evaluation.

Project Status: Completed

URL for project: http://www.msac.gov.au/internet/msac/publishing.nsf/Content/1582-public

Year Published: 2020

URL for published report: http://www.msac.gov.au/internet/msac/publishing.nsf/Content/28026E8B770E4596CA25847F002141B3/$File/1582-DCAR%2017_08_21.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Australia

Organisation Name: Adelaide Health Technology Assessment

Contact Address: School of Public Health, Mail Drop 545, University of Adelaide, Adelaide SA 5005, AUSTRALIA, Tel: +61 8 8313 4617

Contact Name: ahta@adelaide.edu.au

Contact Email: ahta@adelaide.edu.au

Copyright: <p>Adelaide Health Technology Assessment (AHTA) on behalf of NICS</p>