Abstract: SA-PO112
Early Renal Response Biomarkers in Lupus Nephritis: Data from the AURION and AURA Trials
Session Information
- Clinical Glomerular Disorders: Biomarkers and Molecular Profiling
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Glomerular
- 1005 Clinical Glomerular Disorders
Authors
- Huizinga, Robert B., Aurinia Pharmaceuticals, Victoria, British Columbia, Canada
- Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Tumlin, James A., University of Tennessee College of Medicine, Chattanooga, Tennessee, United States
- Truman, Matt, Aurinia Pharmaceuticals, Victoria, British Columbia, Canada
- Solomons, Neil, Aurinia Pharmaceuticals, Victoria, British Columbia, Canada
Background
During treatment of lupus nephritis (LN) early biomarkers of complete, partial and no renal response (CR, PR, NR) would allow changing therapy in patients destined to not respond to their current treatment. Changes in complement and proteinuria after 8 weeks of therapy were shown to predict renal response at 6 months in the ALMS LN trial. To validate these biomarkers their performance was tested in the recently completed AURION and AURA LN trials.
Methods
Data was taken from the AURION 10 patient open-label study of voclosporin (VCS) 23.7 mg po BID, MMF and steroids in active LN, and from the AURA 265 patient randomized double-blind study of voclosporin in active LN. In AURA patients were dosed with voclosporin 23.7 mg po BID, 39.5 mg po BID or placebo, MMF and steroids. First morning voids (FMVs), 24 hour urine collections C3, C4 and anti-dsDNA were collected throughout. Normalization of C3 or C4 at week 12 and 25% reduction in Week 8 UPCR (25%UPCR) were used as predictors of CR at 24 and 48 weeks.
Results
In AURION, a 25%UPCR was 71% and 75% sensitive in predicting CR at weeks 24 and 48, but specificities were 33% and 25% respectively. Similar sensitivities (99% and 90%) for predicting 24 and 48 week CR were seen for a 25%UPCR, specificity remaining low (33% and 33%).In AURION C3 or C4 normalization at week 12 was not sensitive (29 and 25%), but specific (100% and 75%) for predicting 24 and 48 week CR. Similarly in AURA, C3 or C4 were not sensitive, but C3 was 80% and 81% specific while C4 was 77% and 76% specific for predicting 24
and 48 week CR. Change in anti-dsDNA has similar specificities as C3 or C4 but lower sensitivity for predicting CR at 24 and 48 weeks.
Conclusion
As active lupus nephritis flares cause damage within the renal matrix, a more rapid way of predicting CR at 24 or 48 weeks is needed. A rapid predictor should demonstrate both high sensitivity and specificity providing clinicians confidence for changing therapy earlier rather than waiting for 24 or 48 weeks. Use of a 25% reduction in Week 8 UPCR plus C3 normalization at week 12 provides clinicians a sensitive (99%) and specific (80%) method of predicting CR at 24 weeks. This same combination also provides clinicians a sensitive (90%) and specific (81%) method of predicting CR at 48 weeks. Future clinical trials should consider the use of this methodology.
Funding
- Commercial Support –