Eculizumab Prevents Thrombotic Microangiopathy: Long-Term Follow-up Study of Patients with Atypical Hemolytic Uremic Syndrome
Notice bibliographique
Résumé
Abstract Background: Eculizumab was demonstrated to effectively treat and prevent thrombotic microangiopathy (TMA) and to improve renal function and hematologic parameters for up to 2 years in4 previous prospective clinical trials and in 1 retrospective study of patients with atypical hemolytic uremic syndrome (aHUS). Patients in these studies enrolled in a long-term follow-up study, in which rates of TMA were evaluated during eculizumab treatment and during discontinuation from eculizumab. Methods: Data were gathered from an ongoing, observational, multicenter study of aHUS patients treated with eculizumab in 5 prior clinical studies. The primary endpoint was TMA event rate post-parent study during on-treatment (ON; among patients receiving eculizumab) and off-treatment (OFF; among patients who discontinued eculizumab) periods. Results: As of March 28, 2015, 87 patients, including 35 children <18 years of age (40%) and 52 adults ≥18 years of age (60%), enrolled in the study (Table). Of these, 76 patients had ON and 39 patients had OFF treatment periods with median follow-up of 26.1 and 20.1 months, respectively. A reduced dosage of eculizumab was received by 33 of 87 patients (38%). Seventeen of 39 patients (44%) reinitiated eculizumab after therapy discontinuation. The TMA event rates were 7.3 and 19.9 per 100 patient-years for ON and OFF patients, respectively. The rate of TMA in ON patients was greater in those receiving reduced dosing compared with label recommendations (Table). OFF patients had higher estimated glomerular filtration rates at time of discontinuation than ON patients. Age, frequencies of higher-risk complement factor mutations (CFH, C3, or CFB) and kidney transplant status were not different between ON and OFF patients. Factors that independently predicted TMA events included: ON treatment status (compared with OFF; hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.07‒0.49; P<0.001), higher-risk mutations (compared with no mutation; HR, 5.51; 95% CI, 1.61‒18.84; P=0.007), and lower-risk mutations (compared with no mutation; HR, 3.70; 95% CI, 1.05‒13.02; P=0.04). Conclusions: The TMA event rate was 2.7-fold higher after eculizumab discontinuation compared with patients receiving ongoing eculizumab therapy. TMA event rates were lowest during on-label dosing, higher during reduced dosing, and highest during off-treatment periods. These findings suggest that patients with aHUS have a progressive increase in the risk of TMA events during periods of reduced dosing and after discontinuation of eculizumab, compared with on-label eculizumab dosing. Disclosures Greenbaum: Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Fakhouri:Alexion Pharmaceuticals: Consultancy. Kincaid:Alexion Pharmaceuticals: Employment, Equity Ownership. Licht:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillon: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mix:Alexion Pharmaceuticals: Employment, Equity Ownership. Provôt:Alexion Pharmaceuticals: Honoraria. Rondeau:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sheerin:Alexion Pharmaceuticals: Honoraria. Wang:Alexion Pharmaceuticals: Employment, Equity Ownership. Menne:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Comment cette classification a été obtenuedéplier
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) | 0,000 | 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.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».