#468 Voclosporin-based, triple-immunosuppressive therapy vs high-dose glucocorticoid-based dual-immunotherapy for lupus nephritis: a propensity analysis
Bibliographic record
Abstract
Abstract Background and Aims Voclosporin is a second generation calcineurin inhibitor (CNI) approved for the treatment of adults with active lupus nephritis (LN) in combination with immunosuppressive therapy. An integrated analysis of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies concluded that combining voclosporin with lower-dose mycophenolate mofetil (MMF, 2 g/day) and low-dose glucocorticoids (GCs) led to significantly greater and earlier reductions in proteinuria when compared to MMF and GCs alone. This is an important finding as early reduction in proteinuria is associated with improved long-term kidney survival and mortality. Yet, dual-immunosuppressive regimens consisting of high-dose glucocorticoids and either intravenous cyclophosphamide (IVC) or higher doses of MMF (>2 g/day) continue to be frequently used for the initial management of active LN despite their association with incomplete efficacy and dose-dependent toxicities. Method All three studies enrolled participants with active LN. In AURA-LV and AURORA 1, participants received voclosporin 23.7 mg BID in combination with MMF (target 2 g/day) and oral GCs (25 mg/day tapered to 2.5 mg/day by Week 16). In ALMS, MMF (target 3 g/day) or IVC (0.5 to 1.0 g/m2/month × 6) was added to oral GCs initiated at a maximum dose of 60 mg/day, tapered every 2 weeks to 10 mg/day. Propensity score methodology was used to generate groups of matched participants (ALMS [MMF and IVC] vs. AURA-LV/AURORA 1 [voclosporin]) based on demographic and disease characteristics. Safety and efficacy were assessed at 3 and 6 months. Results Propensity matching identified 179 pairs of participants with similar demographics and baseline disease characteristics. Mean cumulative exposure to GCs was more than 2-fold higher in the IVC and MMF cohorts of ALMS than AURA-LV/AURORA 1 participants over both 3 and 6 months. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants of ALMS, although more participants in AURA-LV and AURORA 1 reported hypertension and anemia (Table 1). Due to the known hemodynamic effects of calcineurin inhibition, there was a small decrease in mean eGFR in the AURA-LV/AURORA 1 participants in the first few weeks of treatment after which mean eGFR remained stable; AURA-LV/AURORA 1 participants also had an increased rate of events of GFR decreased. The incidence of serious AEs was similar across treatments. In the first 3 months of treatment, significantly more AURA-LV/AURORA 1 participants achieved a reduction in UPCR >25% from baseline (91.6% vs 69.3%; odds ratio [OR] 4.75, 95% confidence interval [CI] 2.56, 8.84; p < 0.0001). Over six months of treatment, mean (SD) change from baseline in UPCR was −3.1 (2.9) g/g in voclosporin-treated patients in AURA-LV and AURORA 1 compared to −2.4 (3.3) g/g in IVC- or MMF-treated participants in ALMS (Fig. 1). Conclusion Voclosporin-based, triple immunosuppressive therapy was associated with an improved safety profile as well as greater and earlier reductions in proteinuria compared to more conventional dual immunosuppressive regimens. These data support treatment guidelines for active LN that recommend both minimizing patient exposure to GCs and use of a multi-targeted treatment regimen as initial therapy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.005 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".