THERAPEUTIC DRUG MONITORING OF AZATHIOPRINE AND TACROLIMUS IN SLE PREGNANCIES: PRELIMINARY RESULTS FROM THE LEGACY COHORT
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".