Eculizumab (ECU) Significantly Improves Health-Related Quality of Life (HRQoL) in Patients with Atypical Hemolytic Uremic Syndrome (aHUS)
Notice bibliographique
Résumé
Abstract Abstract 4772 Background aHUS is a rare, genetic, life-threatening, disease caused by chronic uncontrolled complement activation, which leads to systemic thrombotic microangiopathy (TMA). Despite plasma exchange/infusion (PE/PI), >50% of patients (pts) will either die, require kidney dialysis or have permanent renal damage within the first year of diagnosis. In addition to causing progressive organ damage, the uncontrolled complement activation and subsequent TMA might be expected to impact HRQoL. In 2 prospective, controlled, single-arm phase II trials of aHUS pts receiving ECU, a terminal complement inhibitor, TMA was stopped, there was no longer a need for PE/PI or new dialysis. In one of the trials (C08-002), dramatically, 4/5 pts on dialysis permanently discontinued dialysis as of most recent follow-up. The current analysis evaluates the impact of ECU on HRQoL in aHUS pts. Methods In trial C08-002, 17 pts with aHUS resistant to PE/PI (persistent TMA despite ≥4 PE/PI sessions 1 wk before screening) received ECU. In trial C08-003, 20 pts previously received chronic PE/PI (≥1 every 2 wks and <3 per wk for ≥8 wks prior to ECU). Clinical data, including pt-reported outcomes, were collected at baseline and through the 26-wk treatment and ongoing extension studies up to data cut-off (mean [SD] duration of ECU treatment: C08-002=58 [29] wks and C08-003=60 [12] wks). HRQoL was measured with the EQ-5D self-reporting questionnaire and a 20-cm visual analogue scale (VAS) validated for a number of disease populations. EQ-5D has 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and 3 levels (no problem, some problems and extreme problems). Change in HRQoL was calculated using the US time trade-off (TTO) index and VAS valuation techniques, and ANOVA analysis. A change of >0.06 is considered a clinically meaningful change Results C08-002: 15/17 pts received ECU until Wk 26 (2 discontinued at Wks 1 and 6; protocol violation and an adverse event unrelated to ECU, respectively) and 13 continued into the extension study. Median age=28 yrs and 29% were on dialysis immediately prior to ECU. Median time from diagnosis to screening =10 mo. All patients had eGFR ≤60 mL/min/1.73m2. C08-003: 20 pts received ECU for 26 wks and 19 continued into the extension study. Median age=28 yrs. Median time from diagnosis to screening=48 mo. Median duration of eGFR ≤60 mL/min/1.73m2=180 days at baseline. HRQoL: In both cohorts of distinct trial pts, ECU substantially improved HRQoL through Wk 26, and sustained this thereafter during long-term ECU therapy (table). In trial C08-002, improvements were seen as early as Day 7 (0.12, p=0.0346). Point estimate improvement (95%CI) in HRQoL from baseline to1 yr was 0.32 (0.27-0.36) for C08-002 and 0.09 (0.05-0.14) for C08-003. On an individual pt basis, 87% and 73% of C08-002 and C08-003 pts, respectively, achieved a clinically meaningful change that represented a clinically important large or moderate improvement in HRQoL measures, respectively. Conclusions aHUS pts have an impaired HRQoL both from a direct impact of aHUS morbidity and management requirements (such as PE/PI), but also from the systemic nature of the disease. In patients with aHUS, significant improvements in HRQoL were achieved rapidly with ECU (as early as Day 7). Sustained long-term treatment with ECU maintained the improvements in HRQoL. Disclosures: Muus: Alexion: Honoraria, Research Funding. Off Label Use: The research described is a clinical trial of eculizumab in patients with aHUS, an indication in which its use is not approved. Licht:Alexion: Honoraria, Research Funding. Goodship:Alexion: Honoraria, Research Funding. Greenbaum:Alexion: Honoraria, Research Funding. Bedrosian:Alexion: Employment. Loirat:Alexion: Honoraria, Research Funding. Legendre:Alexion: Honoraria, Research Funding.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 tête enseignante, pas un consensus.
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