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Abstract: SA-PO892

Analysis of the NefIgArd Part A Study Population Confirms Nefecon Reduces Levels of Dietary Antigen-Specific IgA in Patients with IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Cotton, Vicky, University of Leicester, Leicester, United Kingdom
  • Karaer, Irem, University of Leicester, Leicester, United Kingdom
  • Thomas, Roisin Clare, University of Leicester, Leicester, United Kingdom
  • Molyneux, Karen, University of Leicester, Leicester, United Kingdom
  • Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Group or Team Name

  • IgA Nephropathy Group.
Background

Nefecon, the targeted-release formulation of budesonide, is delivered to the gut-associated lymphoid tissue (GALT) of the terminal ileum, a major site of immunoglobulin A (IgA) production. The Phase 3, double-blind, randomized controlled clinical trial NefIgArd tested the efficacy of Nefecon in patients with IgA nephropathy (IgAN) at high risk of progressive kidney disease despite optimized supportive care. The trial comprised 9 months of treatment with either placebo or Nefecon 16 mg/day, and a 3-month (Part A) or 15-month (Part B) off-drug observational follow-up period. Treatment with Nefecon 16 mg/day significantly reduced proteinuria after 9 months of treatment compared with placebo (p=0.0003) and this effect was maintained, along with preservation of estimated glomerular filtration rate (p<0.0001), over the 15-month off-drug observational follow-up period.

The aim of this study was to determine the effect of Nefecon treatment on circulating levels of dietary antigen-specific IgA, secretory IgA, and a marker of gut permeability, fatty acid-binding protein 2 (FABP2).

Methods

Circulating levels of anti-gliadin IgA, anti-casein IgA, secretory IgA and FABP2 were measured in baseline serum samples and 3, 6, and 9 months after randomization during Part A of the NefIgArd trial using enzyme-based immunosorbent assays. Comparisons between placebo and Nefecon-treated groups were made at each study time point using unpaired t-tests, with a significance level of p<0.05.

Results

Treatment with Nefecon 16 mg/day significantly reduced levels of anti-gliadin IgA at 3 months (p=0.044), 6 months (p=0.029), and 9 months (p=0.027), and levels of anti-casein IgA at 9 months (p=0.023), compared with antibody levels at baseline. These data are consistent with Nefecon 16 mg/day results obtained in the Phase 2b NEFIGAN clinical trial. No significant changes were seen in levels of secretory IgA or FABP2.

Conclusion

Reductions in IgA antibodies against mucosally encountered antibodies confirm a local mucosal effect of Nefecon in IgAN. This effect is likely mediated by a direct action on GALT B cell IgA production rather than an effect on gut permeability and increased antigen exclusion.