Abstract
BACKGROUND: Nefecon is an oral, targeted-release formulation of budesonide approved to reduce kidney function loss in patients with immunoglobulin A nephropathy (IgAN). In the phase 3 NefIgArd trial, 9 months of nefecon treatment preserved estimated glomerular filtration rate (eGFR) and reduced urine protein-creatinine ratio versus placebo, for 15 months post-treatment. A modelling analysis was conducted to predict nefecon's long-term benefits on clinical outcomes. METHODS: A published linear regression model was used to extrapolate nefecon's effect on the eGFR slope in NefIgArd to predict its effect on the clinical outcome of kidney failure, eGFR <15 ml/min/1.73 m(2), or sustained doubling of serum creatinine. This model was applied to registry data from patients with IgAN at Leicester General Hospital (LGH), whose records were matched to individual NefIgArd patients on the basis of their urine protein-creatinine ratio and eGFR values. RESULTS: A total of 1684 LGH-NeflgArd 'matched pairs' were obtained. Nefecon was predicted to delay the time to clinical outcome by 12.8 years (95% confidence interval 4.8-27.9), with median time to outcome of 9.6 years for patients receiving supportive care only versus 22.4 years for nefecon-treated patients. The NeflgArd 2-year eGFR slope yielded a log hazard ratio for the clinical outcome of 0.38 (95% confidence interval 0.21-0.63), a 62% risk reduction versus placebo. Of patients receiving only supportive care, 52% were modelled to have a clinical outcome within 10 years versus 24% of nefecon-treated patients. CONCLUSION: This modelling analysis indicates that the eGFR benefit seen with nefecon predicts a substantial delay in progression to kidney failure.