OBJECTIVES: To determine whether the anti-PLA2R test may be cost-effective for identifying patients with primary Membranous Nephropathy (MN) and avoiding unnecessary invasive and costly biopsies in these patients. As an early-stage assessment, the analysis focused on identifying key uncertainties to inform future research requirements.

METHODS: A short-term decision tree model was used to compare standard care (biopsy for all) vs. anti-PLA2R (initial biopsy only for patients with negative anti-PLA2R) from a UK NHS perspective. Test accuracy was informed by a recent meta-analysis (anti-PLA2R ELISA [20 RU/mL cut-off, n=33 studies]: 63.1% sensitivity. 95.5% specificity; anti-PLA2R IIF: 70.5% sensitivity, 98.6% specificity). Costs included clinical appointments, investigations, biopsy complications, and unnecessary treatment costs for patients receiving a false-positive (FP) result. Projected life years gained (LYG) resulting from reduced biopsy mortality was captured; however no data was available to inform potential quality-of-life impacts associated with FP results. Extensive sensitivity analyses were undertaken to assess the impact of model parameters and assumptions on the results; and a threshold analysis explored what level of QALY loss would be required in the FP group to render the test no longer cost-effective.

RESULTS: Over a cohort of 1,000 patients, the anti-PLA2R ELISA testing strategy is expected to save £100 per patient and avoid 173 unnecessary biopsies, with a projected 2.87 LYG. The IIF test is associated with slightly higher savings (£131), avoided biopsies (179) and LYG (3.04). Key influential parameters were test specificity, investigation costs, and the proportion of FP cases assumed to receive costly Rituximab treatment (base case = 50%). Threshold analysis indicates that 4.99 QALYs would need to be lost in the FP group (n=33) to produce negative net benefit.

CONCLUSIONS: There is clear potential for the anti-PLA2R test to save NHS costs. Future research should address uncertainty around clinical management and outcomes for patients receiving a FP result.