Kidney Week

Abstract: TH-OR108

Relationship Between Treatment Effects for Proteinuria and eGFR Slope over 2 Years in Patients with IgA Nephropathy

Session Information

• Mostly IgA Nephropathy
  November 07, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
  Abstract Time: 04:30 PM - 04:42 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Stone, Andrew M., Stone Biostatistics Ltd, Crewe, United Kingdom

Andrew M. Stone



Andrew Stone (MSc, CStat) is a consultant biostatistician who has 27 years of experience in the pharmaceutical industry. He led the oncology therapeutic area for biostatistics at AstraZeneca in various roles for nearly 10 years. In addition, he has published a number of papers related to trial design and analysis.

• Cattran, Daniel C., Toronto General Hospital, Toronto, Ontario, Canada

Daniel C. Cattran,

• Floege, Jürgen, RWTH University of Aachen, Aachen, Germany

Jürgen Floege,

• Lafayette, Richard A., Stanford University, Stanford, California, United States

Richard A. Lafayette,

• Tesar, Vladimir, General University Hospital in Prague, Prague, Prague, Czechia

Vladimir Tesar,

• Trimarchi, Hernan, Hospital Britanico de Buenos Aires, Buenos Aires, Argentina

Hernan Trimarchi,

• Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad H. Rovin,

• Kristensen, Jens, Calliditas Therapeutics AB, Stockholm, Sweden

Jens Kristensen,

• Barratt, Jonathan, University of Leicester, Leicester, United Kingdom

Jonathan Barratt,

Background

A challenge for evaluating treatments for IgA nephropathy (IgAN) is the usually long time course for progression to ESKD. Recent meta-analyses have separately explored the role of proteinuria reduction and the rate/slope of eGFR decline as surrogate endpoints. In this meta-analysis we describe the relationship between treatment effects on proteinuria, recorded at 1 year, and 2-year eGFR (CKD-EPI) slope.

Methods

Study level data from 1037 patients in 12 IgAN studies, aggregated into 7 study groupings, were obtained from the databook provided at the March 2018 NKF/FDA/EMA workshop. A weighted linear regression was performed to quantify the relationship between baseline adjusted treatment effects for proteinuria, expressed as the log of the ratio of geometric means, and treatment effects for total 2-year eGFR slope, expressed as the difference in arithmetic means. Studies were weighted in inverse proportion to the variance of the 2-year eGFR slope treatment effect.

Results

There was a statistically significant association seen between treatment effects for proteinuria at 12 months and treatment effects for 2-year eGFR slope for the IgAN studies, p=0.043. On average, the between arm, annualized difference in the rate of decline in eGFR was estimated to increase by 4.53 ml/min/1.73m²/year (95%CI: 0.21, 8.84) for every 1 log (63%) reduction in the proteinuria treatment arm ratio.

Conclusion

In IgAN treatment effects on 12m proteinuria are reasonably likely to predict subsequent treatment differences in the rate of decline in eGFR over 2 years.