Abstract: SA-PO688
Voclosporin Induces Systemic Lipidomic Alterations: Implications in the Remission of Lupus Nephritis
Session Information
- Glomerular Diseases: Clinical, Outcomes, Trials - III
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials
Authors
- Afshinnia, Farsad, University of Michigan, Ann Arbor, Michigan, United States
- Rehaume, Linda M., Aurinia Pharmaceuticals Inc, Victoria, British Columbia, Canada
- Cross, Jennifer, Aurinia Pharmaceuticals Inc, Victoria, British Columbia, Canada
- Huizinga, Robert B., Aurinia Pharmaceuticals Inc, Victoria, British Columbia, Canada
- Pennathur, Subramaniam, University of Michigan, Ann Arbor, Michigan, United States
Background
Voclosporin is a novel calcineurin inhibitor indicated for the treatment of adults with active lupus nephritis (LN). Cardiovascular disease (CVD) is a major cause of morbidity and mortality in SLE patients, and LN is an independent CVD risk factor. The AURORA 1 trial showed favorable renal clinical response and changes in traditional lipoproteins with voclosporin. We hypothesize that the beneficial therapeutic response is mediated in part by alteration in circulating lipids.
Methods
In a lipidomic analysis, 918 serum lipids in 14 classes from baseline and week 52 of randomly selected participants from control (placebo) (N=30) and voclosporin (N=28) arms of the AURORA 1 trial (ClinicalTrials.gov, NCT03021499; EudraCT, 2016–004045–81) were compared. All patients received MMF and low-dose steroids. The difference of lipids at week 52 from baseline was calculated, z-score standardized, and used in mixed linear models.
Results
The alterations of lipid class levels were assessed as a function of voclosporin effect and by achievement of either complete renal response (CRR) or partial renal response (PRR) (Table). Voclosporin and renal clinical response (CRR or PRR) contributed to decline in CERs and TAGs and increase in DCERs and PIs independent of each other. Results indicate the additive effects of voclosporin and renal clinical response on alteration of corresponding lipids. Voclosporin, CRR and PRR were independently associated with alteration of PC(C16), PIs, and TAGs. An integrative analysis showed significant correlations between saturated DAGs and MAGs (C>16), TAGs, SMs, CERs, unsaturated PEPs, and palmitoyl PCs(C16) after controlling for CRR or PRR.
Conclusion
CERs, DCERs, PIs, and TAGs are altered by voclosporin. Alterations of PC, PI and TAGs correlate with renal outcome independent of voclosporin. Collectively, these findings suggest that voclosporin reduces lipogenesis by decreasing incorporation of fatty acid precursors, and a favorable therapeutic response is mediated in part by promotion of change in corresponding lipid class.
Funding
- Commercial Support –