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Abstract: PO1455

Treatment with Targeted Release Formulation Budesonide (Nefecon) Modulates the Complement System in Patients with IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Pérez Alós, Laura, Kobenhavns Universitet Sundhedsvidenskabelige Fakultet, Kobenhavn, Denmark
  • Molyneux, Karen, University of Leicester, Leicester, Leicestershire, United Kingdom
  • Fellstrom, Bengt C., Akademiska sjukhuset, Uppsala, Sweden
  • Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
  • Garred, Peter, Kobenhavns Universitet Sundhedsvidenskabelige Fakultet, Kobenhavn, Denmark
Background

The NEFIGAN trial (NCT01738035) evaluated the effect of a novel targeted-release investigational formulation of budesonide (TRF-budesonide [Nefecon]) in the treatment of IgA nephropathy (IgAN). Participants in this Phase 2b trial were randomly assigned placebo, Nefecon 8 mg or 16 mg/day, and samples were collected at baseline (0 months), at the end of the treatment (9 months) and at the end of the study (12 months). In this exploratory study we evaluated the effect of Nefecon treatment on the circulating levels and urinary excretion of a panel of complement components.

Methods

Plasma and urine levels of complement proteins (C4c, C3bc and soluble C5b-9) and ficolin-1, -2 and -3, MBL, CL-11, MASP-3, MAP-1 and PTX-3 were measured using in-house sandwich-ELISAs. Treatment differences between baseline, end of treatment and end of study were assessed by mixed-effects model analysis. The effect of the treatment correcting for the baseline was assessed by multiple linear regression. Significance: p < 0.05. Urinary proteins were adjusted for creatinine excretion.

Results

Circulating levels of MASP-3 were decreased in a dose-dependent manner after treatment (p=0.0313 Nefecon 8 mg/day, p=0.0080 Nefecon 16 mg/day). MBL/creatinine was significantly reduced in the urine by both doses of Nefecon compared with placebo (p<0.0001 Nefecon 8 mg and 16 mg/day). CL-11/creatinine levels were also significantly reduced in a dose-dependent manner after Nefecon administration (p<0.0411 Nefecon 8 mg/day, p<0.0095 Nefecon 16 mg/day). Complement activation markers and ficolin-3 levels were detectable in urine but levels remained unaltered.

Conclusion

Treatment with Nefecon modulates components of both the alternative (MASP-3) and lectin (MBL and CL-11) pathways of complement, two pathways known to be important in mediating kidney damage in IgAN. These initial observations warrant further investigation.

Funding

  • Commercial Support