Eculizumab Is an Effective Treatment for Atypical Hemolytic Uremic Syndrome in Patients with or without Identified Genetic Complement Mutations or Complement Factor H Auto-Antibodies.
Notice bibliographique
Résumé
Abstract Abstract 2085 Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare chronic disorder characterized by persistent uncontrolled complement activation that results in life-threatening systemic thrombotic microangiopathy (TMA). In an estimated 50%–70% of patients (pts) with aHUS, uncontrolled complement activation can be attributed to identified genetic mutation(s) in complement regulatory factors and/or the presence of complement factor H auto-antibodies (CFH auto-Abs); newly identified complement mutations continue to be reported in the medical literature. For the 30%–50% of pts who currently have no identified genetic mutation/CFH auto-Abs, the overall risk of end-stage renal disease or death is high and similar to that observed in pts with known genetic mutation(s)/CFH auto-Abs, supporting the need for immediate management of disease in all aHUS pts regardless of mutation/CFH auto-Ab status. Eculizumab, an anti-C5 monoclonal antibody that inhibits terminal complement activation, is the only approved treatment for aHUS. Chronic eculizumab treatment has been proven to inhibit systemic TMA via terminal complement inhibition, improve renal function, and reduce or eliminate the need for plasma exchange/infusion (PE/PI) and dialysis. Furthermore, earlier eculizumab treatment has been associated with greater clinical improvement. The purpose of this analysis was to evaluate the relative efficacy of eculizumab in aHUS pts with or without identified genetic complement mutation(s)/CFH auto-Abs based on data from 3 clinical studies. Methods: This report summarizes a subgroup analysis of efficacy outcomes based on the presence or absence of identified genetic mutation(s)/CFH auto-Abs in 3 aHUS studies: 2 controlled, prospective studies (pts aged ≥12 y), and 1 retrospective study (pts aged <18 y). Results: Across the 3 studies, 24%–41% of pts had no identified genetic complement mutation or detectable CFH auto-Abs. The efficacy of eculizumab was similar regardless of mutation/CFH auto-Ab status (Table). Conclusions: Across 3 studies investigating the efficacy of eculizumab treatment in aHUS pts, our analysis shows that improvements in hematologic, renal, and supportive care interventions (PE/PI, dialysis) outcomes were similar in pts with or without identified genetic complement mutation(s)/CFH auto-Abs. Given that (1) genetic testing often requires several months to complete, (2) uncontrolled complement activation places aHUS pts at risk of life-threatening systemic TMA events and organ damage, and (3) earlier intervention with eculizumab is associated with greater clinical improvement, we conclude that the results of this analysis provide a rationale for initiating eculizumab as first-line therapy at the time of clinical diagnosis of aHUS, without the availability of genetic testing results Disclosures: Goodship: Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Legendre:Alexion Pharmaceuticals: Speakers Bureau. Licht:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Muus:Alexion Pharmaceuticals.: Sat on advisory board of Alexion Pharmaceuticals. Other. Bedrosian:Alexion Pharmaceuticals: Employment, Equity Ownership. Loirat:Alexion Pharmaceuticals: Coordinator of Alexion trials of eculizumab in atypical HUS for France. Honoraria for conferences. Other.
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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.
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| 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) | 0,002 | 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
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