#2651 Sustainability and depth of UPCR reduction in patients with primary IgAN treated with nefecon: a secondary analysis of the Phase 3 NefIgArd trial
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».