Long-Term Follow-up of Hypereosinophilic Syndrome Patients Treated with Mepolizumab: A Nationwide Real-Life Study of 59 Patients
Notice bibliographique
Résumé
Background Mepolizumab, a humanized monoclonal antibody directed against IL-5, has proven efficacious for the treatment of FIP1L1 ∷ PDGFRA ( F/P)-negative Hypereosinophilic Syndrome (HES) in two randomized controlled trials with short term follow-up. However, both its efficacy and safety profiles on the long term are unknown. Methods All F/P-negative HES patient treated with mepolizumab in France from 2003 to 2022 in either GlaxoSmithKline-sponsored randomized trials (MHE100185 and HES200622) or long-term access programs (MHE100901 and MHE10417) were included. For each study visit, we retrospectively collected the following data: drug doses (and spacing), HES-disease status, absolute eosinophil counts (AEC), and doses of oral corticosteroids (OCS). Clinical remission (CR) was defined as the absence of symptoms related to HES. Complete hematological remission (CHR) was defined as an AEC < 0.5 x 10 9/L, and relapse by the occurrence of new or worsening of HES-related symptoms, irrespective of either AEC or increase of HES treatments. Relapse-free survival was modeled using a Kaplan-Meier method. We also assessed the rates of “super responses”, a new outcome measure defined as the combination of both CR, CHR and complete withdrawal of OCS at last follow-up. Results and discussion Data were available for 64 out of the 80 patients identified. All patients ultimately received 300mg subcutaneous mepolizumab, but 27 (45.8%) patients had initially been started on higher doses (700 or 750 mg intravenous). Five patients were excluded because of misdiagnoses despite initially high AEC and HES-mimicking presentation (IgG4-related disease (n=1), Castleman's disease (n=1), lymphoma (n=2) and STAT6 gain-of-function mutation (n=1)). Ultimately, the study population consisted of 59 patients (idiopathic HES, n=51; lymphocytic HES, n=8) with chronic HES sensitive to high-dose OCS yet who remained OCS-dependent on the long run (median [IQR] dose of OCS at baseline: 11 [9-20] mg/d). In median, patients had two organs involved, with gastro-intestinal, respiratory, and cutaneous manifestations being the most frequent symptoms. After a median follow-up of 4.5 [2.5-12.3] years, 11 patients (19%) relapsed, among whom five were clearly related to prior mepolizumab spacing to more than four weeks between injections (Figure 1). In details, most of the patients were in CR (n=55, 93%) and/or in CHR (n=56, 95%) at last follow-up, including 38 (64%) OCS-free patients who fulfilled criteria for super response. No baseline predictive factor for super response was evidenced. When focusing on the 21 (36%) patients with more than eight years of follow-up (median 14.4 [12.2-17.3] years), outcomes tended to be the same as those of the overall population. At last follow-up more than 70% of patients were able to space mepolizumab's infusions for more than four weeks (median time between two injections at last follow-up: 8 [4-11] months). Ultimately, four patients were able to discontinue mepolizumab without subsequent relapse with more than two years of follow-up. There was no new safety signal, and no patient withdrew mepolizumab due to a treatment-related adverse event. Conclusion Mepolizumab remains highly efficacious in the long-term (including in patients with more than 10 years of follow-up), enabling sustained disease remission despite tapering of OCS and spacing of injections. Very few cases of mepolizumab failure were identified, among which the leading cause was HES misdiagnosis.
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) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 ».