THERAPEUTIC DRUG MONITORING OF AZATHIOPRINE AND TACROLIMUS IN SLE PREGNANCIES: PRELIMINARY RESULTS FROM THE LEGACY COHORT
Notice bibliographique
Résumé
PV256 / #543 Poster Topic: AS24 - SLE-Treatment Background/Purpose Pregnant SLE women still face an unacceptably high risk of maternal and fetal morbidity, particularly when their disease is active. How to personalize SLE therapies to optimize pregnancy outcomes remains unknown. Though guidelines strongly recommend azathioprine (AZA) and tacrolimus (TAC) in specific SLE pregnancy scenarios, evidence to guide drug monitoring in this context is nonexistent. Our aim is to evaluate the characteristics of SLE pregnancies according to the levels of AZA metabolites (6-TG) and TAC trough levels at the first pregnancy (baseline) visit. Methods LEGACY is a prospective cohort enrolling unselected SLE pregnancies ≤16 6/7 gestational weeks at 7 Systemic Lupus International Collaborating Clinics. We record demographics, disease activity, and drugs. In addition, whole blood samples are collected at baseline to determine AZA metabolites (eg, erythrocyte-free 6-thioguanine, 6-TG) and trough TAC levels if applicable. The present study included Montreal LEGACY participants prescribed either AZA or TAC ≥3 months prior to their first pregnancy visit. We characterized AZA metabolite and TAC levels as continuous and categorical variables (ie, nonadherent, subtherapeutic, therapeutic, and supra-therapeutic, using established cut-offs in nonpregnant populations). We defined patients as nonadherent if they had undetectable or barely detectable levels despite appropriate dosing. Results Of 70 LEGACY pregnancies enrolled in Montreal, 23 (33%) and 6 (9%) were prescribed AZA and TAC, respectively. Among those prescribed AZA, only 9% had therapeutic levels, while 91% were subtherapeutic or nonadherent (Table 1). Compared to those with therapeutic levels, pregnancies with subtherapeutic or nonadherent AZA levels were more likely to occur in women of non-Caucasian ethnicity/race, on steroids, with longer SLE duration, and with prior lupus nephritis (Table 2). Among those prescribed TAC, 50% (3/6) had therapeutic levels, while 33% (2/6) and 17% (1/6) were subtherapeutic and supra-therapeutic, respectively. No patients on TAC were identified as nonadherent. Less than half (43%) of pregnancies nonadherent to AZA were in Lupus Low Disease Activity State (LLDAS) at baseline. Of the pregnancies with subtherapeutic TAC levels, 50% (1/2) were not in LLDAS, while all (4/4) pregnancies with therapeutic or supra-therapeutic TAC levels were in LLDAS at baseline. Table 1. Number of pregnancies and mean drug dose at baseline visit according to AZA metabolite (6-TG) and TAC trough levels Table 2. Baseline maternal characteristics stratified according to AZA metabolite (6-TG) and TAC trough levels Conclusions We observed that most SLE pregnancies prescribed AZA had subtherapeutic levels, with nearly a third identified as nonadherent. Pregnancies with lower AZA and TAC levels may be less likely to achieve LLDAS. Despite low numbers, our preliminary results suggest the value of personalized drug monitoring as a novel approach to precision medicine in pregnant SLE women, that might improve efficacy, safety, and adherence in a high-risk population.
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 | 0,003 |
| 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 | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 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 ».