Efficacy and Safety Is Maintained in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan for up to 3 Years
Notice bibliographique
Résumé
Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first complement component 3 (C3) inhibitor for PNH, increased hemoglobin (Hb) levels in complement component 5 inhibitor (C5i)-experienced and -naive adult patients with PNH in 2 phase 3 clinical trials (PEGASUS [NCT03500549] and PRINCE [NCT04085601], respectively). This integrated analysis of data from the pivotal phase 3 trials and the subsequent open-label extension (study 307; NCT03531255) evaluated the long-term efficacy and safety of pegcetacoplan for PNH treatment. Methods: For this integrated analysis, baseline was defined as the initiation of pegcetacoplan, regardless of when in the trials this occurred. Patients initially received pegcetacoplan 1080 mg subcutaneously twice weekly; dose escalations to once every 3 days or 3 times weekly were permitted. Efficacy was evaluated from baseline up to Weeks 132 (2.5 years, PRINCE) and 156 (3 years, PEGASUS) by Hb, lactate dehydrogenase (LDH; upper limit of normal [ULN] 226 IU/L), absolute reticulocyte count (ARC), and indirect bilirubin values; Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores; and transfusion avoidance rates (percentages of patients who did not require a transfusion during treatment). Safety was assessed by incidence of adverse events (AEs) and serious AEs (SAEs) during pegcetacoplan monotherapy for up to 3 years. Results: Of the 133 patients in the phase 3 trials (PEGASUS, 80; PRINCE, 53), 114 enrolled in the extension study (PEGASUS, 64; PRINCE, 50). At least 75% had received a transfusion in the year before enrolling in PEGASUS or PRINCE. Prior to pegcetacoplan initiation, mean (SD) Hb levels were 8.95 (1.09) g/dL in PEGASUS, 9.27 (1.44) g/dL in PRINCE, and 9.08 (1.24) g/dL in the total population; median (interquartile range) LDH levels were 217.0 (184.8, 276.5) IU/L in PEGASUS, 1964.0 (1409.0, 2503.3) IU/L in PRINCE; and mean (SD) FACIT-Fatigue scores were 31.6 (11.7) in PEGASUS, 36.6 (10.0) in PRINCE, and 33.6 (11.3) in the total population. After pegcetacoplan initiation, mean Hb levels markedly improved from baseline and remained stable through Weeks 132 (2.5 years, PRINCE) and 156 (3 years, PEGASUS) ( Figure). Median LDH rapidly decreased and stabilized below the ULN ( Figure). Improvements in ARC and indirect bilirubin were similarly maintained. Average FACIT-Fatigue scores increased (indicating less fatigue) rapidly and were maintained near the general population norm of 43.6. Annual transfusion avoidance ranged from 71%-79% in PEGASUS and 80%-86% in PRINCE, with 52% of patients from PEGASUS avoiding transfusion for up to 3 years of pegcetacoplan treatment and 67% of patients from PRINCE avoiding transfusion for up to 2.5 years. Overall, >92% patients had compliance rates of at least 95%. Over 3 years, most patients experienced an AE; SAEs were reported in 50.0% of patients, with 4.5% experiencing a SAE deemed related to pegcetacoplan. Overall, 17 patients discontinued pegcetacoplan due to an AE; of those, 9 discontinued due to a hemolytic disorder, 7 of which discontinued within 1 year of starting pegcetacoplan. Over 3 years, 4 (3.0%) deaths occurred, none were deemed related to pegcetacoplan; 3 (2.3%) patients experienced a thrombotic event (in the context of multiple associated comorbidities or discontinuation of pegcetacoplan) and no cases of meningitis were reported. Overall, no new or unexpected safety findings were identified. Conclusions: Rapid improvements in Hb, LDH, ARC, indirect bilirubin, and FACIT-Fatigue values were observed and maintained up to 3 years in C5i-experienced patients and up to 2.5 years in C5i-naive patients. The transfusion burden was significantly reduced. No new safety findings were identified. This analysis demonstrates sustained efficacy and continued safety of long-term pegcetacoplan for patients with PNH, regardless of prior C5i treatment.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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) | 0,000 | 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 ».