#2651 Sustainability and depth of UPCR reduction in patients with primary IgAN treated with nefecon: a secondary analysis of the Phase 3 NefIgArd trial
Bibliographic record
Abstract
Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is a chronic immune-mediated kidney disease characterized by galactose-deficient IgA1 (Gd-IgA1) deposition in the glomeruli. Peyer's patches in the gut-associated lymphoid tissue, found in the intestinal mucosa, are a major site of B cells, which are involved in the production of Gd-IgA1. Nefecon is a novel, oral, targeted-release formulation of budesonide, which is released into the distal ileum to allow maximal exposure to B cells in the Peyer's patches. Nefecon is indicated to reduce the loss of kidney function in adults with primary IgAN who are at risk of disease progression. Results from the Phase 3 NefIgArd trial showed that nefecon 16 mg/day stabilized estimated glomerular filtration rate (eGFR) decline and reduced proteinuria over 9 months of treatment and 15 months of observational follow-up in patients with primary IgAN. Here, we present results from a secondary analysis of the NefIgArd trial evaluating the depth and sustainability of the effect of nefecon 16 mg/day on proteinuria. Method Study design and study endpoints have been previously described. Briefly, eligible patients were aged ≥18 years with biopsy-confirmed primary IgAN, eGFR 35-90 mL/min/1.73 m2, proteinuria ≥1 g/24 hours despite optimized renin–angiotensin system (RAS) inhibition, and well-controlled blood pressure. Patients received nefecon 16 mg or placebo daily for 9 months (n = 182 per treatment group) in addition to supportive care (RAS inhibition), followed by a 15-month off-drug observational period on supportive care only. The primary endpoint of the study was the time-weighted average change from baseline in eGFR over the entire 2-year period. This analysis reports the proportion of patients who achieved sustained 30% or 40% urine protein–creatinine ratio (UPCR) reduction for at least 6, 9, 12, or 18 months, as well as the impact of sustained UPCR reduction on eGFR over 2 years. Results Among patients receiving nefecon 16 mg/day in addition to optimized RAS inhibition, 111 (61%), 96 (53%), 93 (51%), and 23 (13%) achieved 30% UPCR reduction for at least 6, 9, 12, and 18 months, compared with 41 (23%), 29 (16%), 25 (14%), and 9 (5%) patients receiving placebo in addition to optimized RAS inhibition, respectively (Fig. 1). A 40% UPCR reduction for at least 6, 9, 12, and 18 months was achieved by 95 (52%), 76 (42%), 72 (40%), and 12 (7%) patients treated with nefecon in addition to optimized RAS inhibition, compared with 28 (15%), 21 (12%), 18 (10%), and 5 (3%) of those treated with placebo in addition to optimized RAS inhibition, respectively (Fig. 2). The effect of nefecon on UPCR reduction was clinically meaningful, with over half of patients receiving nefecon sustaining a ≥30% UPCR reduction for longer than 12 months. Sustained 30% UPCR reductions for at least 6, 9, and 12 months were associated with mean eGFR change from baseline at 24 months of −4.4, −3.6, and −3.3 mL/min/1.73 m2 among nefecon recipients, and corresponding changes of −7.6, −5.9, and −4.9 mL/min/1.73 m2 among placebo recipients, respectively. Overall, eGFR curves showed that a sustained 30% UPCR reduction for 6 months or more was associated with slower eGFR decline, and that patients receiving nefecon had a slower eGFR decline than those receiving placebo irrespective of the duration for which the 30% UPCR reduction was sustained. Conclusion These findings demonstrate that a substantial proportion of patients receiving nefecon is expected to achieve a deep and sustained reduction in proteinuria as a result of the 9-month treatment period, highlighting the disease-modifying effect of nefecon 16 mg/day treatment and providing support for the favorable nefecon effect on eGFR deterioration and kidney function stabilization.
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".