RITUXIMAB SUPER-RESPONDERS: CHARACTERISTICS OF PATIENTS WITH MORE THAN 3 YEARS RESPONSE TO A SINGLE CYCLE OF TREATMENT
Notice bibliographique
Résumé
PV266 / #632 Poster Topic: AS24 - SLE-Treatment Background/Purpose Rituximab has been used to treat SLE for 20 years but efficacy is limited by inadequate B cell depletion. Emerging therapies such as CD19 CAR-T-cells have been reported to induce deeper B cell depletion and thereby drug-free remission up to 18 months. However, with rituximab, we showed that depth of depletion and rate of repopulation were highly variable, and related to patient factors eg, complement levels and FCGR genotype. Using highly sensitive flow cytometry protocol, plasmablast repopulation below 0.0008 x 10^9/L predicted longer response.[1] Anecdotally, we have observed “rituximab super-responders” with sustained remission after 1 cycle of rituximab. The objectives of the study were to assess a) incidence of rituximab-super-response, with or without concomitant immunosuppressant; and b) factors associated with super-response after the first rituximab cycle, with a view to personalize anti-CD20 antibodies in SLE. Methods We conducted an observational study of consecutive rituximab-treated SLE patients in a single center over 20 years who had followed an on-demand retreatment strategy. Usual practice was to continue concomitant immunosuppressants but taper glucocorticoids. Univariable and multivariable logistic regression analyses were performed to identify factors associated with rituximab super-response, with p<0.1 associated with the deviance used for inclusion into the model. Results Of 149 first-cycle-rituximab-treated patients, 114 were included in the study [excluded due to nonresponse in Cycle 1=17; received fixed retreatment at 6-9 months=15; deaths within the first 3 years=2; and discontinued rituximab due to psoriasis=1]. Based on survival curve, we defined super-responders as >3 years (Figure 1). This occurred in 23/114 patients (20%) with median (IQR) duration of response 263 (212,423) weeks. At baseline, rituximab-super-responders had: mean (SD) age 35 (14) years, 20/23 (87%) female, ancestry European=9/23 (39%); South Asian=6/23 (26%), Chinese/SE Asian=2/23 (9%); African=5/23 (22%); and Mixed=1/23 (4%)], concurrent APS 6/23 (26%), disease duration 2.8 (1,5) years, median (IQR) SLEDAI-2K 11 (7,15), and median (IQR) numeric BILAG score 21 (13,25). Sustained suppression of plasmablasts was observed at 3 years: median (IQR) 0.0008 (0.0002,0.0045). 8/23 Rituximab-super-responders (34.8%) were not prescribed immunosuppressants or withdrew them during follow-up (drug-free remission). In multivariable analysis of 114 patients, factors associated with duration of response >3 years were non-European ancestry (OR 4.6, 95% CI 1.6-12.7)) and concurrent APS, (3.2, 0.99-10.35), while longer disease duration (0.89,0.80-0.99 per year) was associated with lower odds of rituximab-super-response. No other factors (age, sex, anti-dsDNA+, low C3/C4, number of antibodies, concomitant immunosuppressant, disease activity score, and active BILAG A/B in 5 most frequent domains) were predictive. Figure 1: Kaplan-Meier plot of relapse-free survival after a first cycle of rituximab Conclusions Sustained drug-free remission is not confined to patients who have received CAR-T CD19 but may be observed following rituximab. 1 in 5 rituximab-treated patients had >3 years response to their first cycle, and 1 in 12 had sustained, immunosuppressant-free remission. Rituximab-super-response is associated with patient characteristics typically denoting disease severity (early disease, non-European ancestry and APS), as well as marked suppression of plasmablast repopulation. This suggests that sustained drug-free remission is a feature of the overall immune environment rather than the modality of B cell killing. Given their safety and low cost, anti-CD20 monoclonal antibodies in early poor prognosis SLE may be preferable to intensive therapy in refractory disease. Future work will include more detailed biomarker evaluation of this cohort. References: [1.] Md Yusof MY. Ann Rheum Dis 2017;76(11):1829-36.
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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 | 0,001 | 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
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 ».