Estimating the Prevalence of Immunoglobulin A Nephropathy (IgAN) in the European Union: A Weighted Average Estimation Approach Utilizing Diagnostic Procedure Frequency in a Rare Disease Setting

Background: When describing the frequency of rare diseases, epidemiologists often have to extrapolate data from small regional studies to wider geographies. For orphan drug application (ODA) in the European Union (EU), prevalence of the target disease within the EU needs to be established which is particularly challenging in presence of geographical variation of the disease.

Objectives: Our objective was to estimate the prevalence of Immunoglobulin A nephropathy (IgAN), a rare disease requiring kidney biopsy for diagnosis with varying occurrence even within one country, in the EU plus United Kingdom (UK) as part of an ODA.

Methods: We performed a comprehensive review of the scientific literature published between 2000 and 2020 to identify population-based IgAN prevalence and incidence estimates, as well as the kidney biopsy rate in European countries. We used a weighted average approach to estimate the IgAN prevalence across 27 EU countries plus UK with a total population of around 514 million inhabitants in 2020. To account for geospatial differences in IgAN frequency, the prevalence was calculated by weighting the individual country estimates by the respective population size. If no recent country-specific prevalence was available, the annual country incidence was multiplied with disease duration which was assumed as 30 years based on the reported time from diagnosis to onset of end-stage kidney disease. If several country-specific prevalence or incidence estimates were available, the most recent and plausible one was used for the overarching prevalence calculation. For countries where only the biopsy rate but neither incidence nor prevalence was published, the incidence was derived from the estimated linear relationship between incidence (y) and biopsy rate (x) in Europe (y=0.1779x). For countries with outdated or no information, we assumed a biopsy rate in the upper range of plausible biopsy rates. Sensitivity analyses were performed to test the assumptions around disease duration and incidence estimates.

Results: In total, data from 16 EU member states, UK and supportive information from two European non-EU countries was used for the prevalence estimation. Country-specific prevalence estimates ranged from 0.2 to 14.4/10,000 population. The weighted average prevalence of IgAN in the EU was 4.7/10,000 population. Sensitivity analyses led to prevalence estimates ranging from 4.8 to 6.5/10,000 population.

Conclusions: Using a weighted average prevalence estimation approach that utilizes all available evidence including diagnostic procedure frequency to estimate prevalence in larger regions can be considered as a strategy to account for geospatial variations of disease frequency.