Effects of atacicept on disease activity in patients with moderate to severe systemic lupus erythematosus: APRIL-SLE randomized trial
Notice bibliographique
Résumé
Atacicept is a fusion protein that inhibits B-cell stimulating factors BLyS and APRIL, which are elevated in systemic lupus erythematosus (SLE). Atacicept 150 mg (A150) was associated with reduced BILAG A and B flares in the APRIL-SLE study. We examined efficacy of atacicept in preventing flares of SLE disease activity by the BILAG organ system and modified SELENA SLEDAI flare index and assessed corticosteroid use during a previously reported trial of atacicept versus placebo (PLC). Subjects with active SLE were treated with corticosteroid taper for 12 weeks. Subjects reaching BILAG C or D at weeks 10 and 12 were randomized at baseline 1:1:1 to receive PLC, atacicept 75 mg (A75) or A150 twice weekly every 4 weeks then weekly for 48 weeks. All patients received standard of care. Analysis was performed in the modified intention-to-treat population. BILAG and SELENA SLEDAI flares and corticosteroid usage were assessed 4 weekly. The A150 arm was terminated early due to two fatal pulmonary infections. A lower proportion of subjects with >1 BILAG system A or B flare was observed in A150 and A75 versus PLC. Proportions of subjects with BILAG flare in each organ system were reduced in A150 versus PLC, except for vasculitis, which had similar proportions between groups. BILAG flares were most commonly observed in mucocutaneous and musculoskeletal systems. Proportions of subjects with severe SELENA SLEDAI flare during treatment in a post-hoc analysis were 19%, 11%, and 13% for PLC, A75, and A150, respectively. There was a dose-proportional decrease in the number of subjects who had at least one increase in steroid dose, and an increase of ≥20 mg/day (Table 1 ). Atacicept induced substantial reductions in Ig levels, which lessened during follow-up but did not fully return to baseline over 24 weeks. Atacicept treatment effect was observed in subjects with BLyS or APRIL levels ≥ median, but not < median. The difference was most pronounced in patients with baseline BLyS and APRIL ≥ median. Atacicept-treated patients with greatest absolute decrease in IgG and IgM experienced fewest new flares. Reduction of the individual BILAG system and severe SELENA SLEDAI flares and corticosteroid use was associated with A150 treatment. Analysis of potential predictive biomarkers identified a subgroup of patients with higher BLyS and APRIL levels at baseline more likely to benefit from treatment. Further studies are required to clarify safety and efficacy of atacicept in SLE patients and associations between biomarkers and clinical response to atacicept.
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 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 ».