417 Safety of long-term dupilumab treatment in adults with moderate-to-severe atopic dermatitis: results from an open-label extension trial up to 5 years
Notice bibliographique
Résumé
Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease requiring long-term management; however, sustained AD treatment with systemic immunosuppressants is not recommended due to safety concerns. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, inhibiting the signaling of these key and central drivers of type 2 inflammation in multiple diseases. Data from the open-label extension (OLE) study, LIBERTY AD OLE (NCT01949311), previously demonstrated acceptable dupilumab safety in adult patients up to 204 weeks (approximately 4 years), consistent with the known safety profile in parent studies. This study aims to assess the long-term safety of dupilumab administered in adult patients with AD up to 5 years (the end of this OLE study). Adults with moderate-to-severe AD who had participated in any dupilumab parent study (phase 1 through phase 3) were enrolled into the long-term, multicenter OLE trial with a duration of up to 5 years. During the OLE, patients were treated with 300-mg dupilumab weekly (qw). In 2019, patients transitioned to 300 mg every 2 weeks to align with approved dosage. Concomitant treatments for AD were permitted, including topical corticosteroids (TCS) and topical calcineurin inhibitors. Because the OLE trial lacked a control arm, LIBERTY AD CHRONOS (NCT02260986) 52-week safety results for adults with moderate-to-severe AD receiving dupilumab 300 mg qw plus TCS were provided as a comparison. Data shown are for the overall study population (n = 2677). Of the 2677 patients who enrolled, 2207 completed treatment up to Week 52, 362 up to Week 172 and 334 up to Week 260. The most common reason for study withdrawals during the OLE study period was dupilumab approval and commercialization in the patient’s country of enrollment [708 (51.3%)]. The exposure-adjusted incidence rate (EAIR) of patients with ≥1 treatment-emergent adverse event (TEAE) was lower in this OLE vs. the 300 mg qw + TCS arm of the 52-week CHRONOS trial (166.0 vs. 322.4 number of patients/100 patient-years). Over this 5-year OLE, 10.6% of patients had ≥1 serious TEAE, 10.0% had ≥1 severe TEAE, 1.2% had ≥1 serious TEAE related to the study drug and 3.8% of patients experienced a TEAE resulting in permanent drug discontinuation. The most common TEAEs observed were nasopharyngitis (28.9%) and conjunctivitis [20.0%, using a narrow customized MedDRA query (CMQ) containing conjunctivitis and related terms conjunctivitis allergic/bacterial/viral, and atopic keratoconjunctivitis]. Of the patients under narrow CMQ, 95.0% reported mild/moderate conjunctivitis TEAEs and 87.7% of conjunctivitis events were recovered/resolved. The safety profile observed in this OLE trial up to 5 years is acceptable and consistent with the known safety profile of dupilumab observed in controlled studies. The EAIRs of TEAEs overall did not increase over time and were lower than previously reported in the 3- and 4-year analyses of this OLE trial and an earlier 52-week placebo-controlled trial.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».