VARIATIONS IN TACROLIMUS WHOLE BLOOD CONCENTRATIONS DURING PREGNANCY AND ITS IMPLICATIONS FOR THERAPEUTIC DRUG MONITORING: A SYSTEMATIC REVIEW AND META-ANALYSIS
Notice bibliographique
Résumé
PV255 / #550 Poster Topic: AS24 - SLE-Treatment Background/Purpose Tacrolimus is a pregnancy-compatible immunosuppressive increasingly used in systemic lupus erythematosus (SLE) pregnancies. Physiological changes throughout pregnancy impact tacrolimus pharmacokinetics, altering the drug’s whole blood concentrations during gestation. However, data is very limited to guide clinicians caring for pregnant women receiving tacrolimus in interpreting tacrolimus trough levels and adjusting the dosage. We completed a systematic review focusing on the variations of maternal tacrolimus trough levels and dosage during SLE and non-SLE pregnancies. Methods Using a combination of relevant search terms and keywords, we systematically searched Embase, Ovid, PubMed, Web of Science and Cochrane Library up to January 2024. All observational studies which measured whole blood tacrolimus trough levels during pregnancy were included without language or date restriction. Studies which were reviews, case reports, abstracts only, non-human, and had no tacrolimus levels during pregnancy were excluded from the review. We then used random-effects models to estimate standardized mean differences (SMD) or mean differences (MD), with 95% confidence intervals (CI) of tacrolimus trough levels and doses before and during pregnancy and in the postpartum. Results: Of 404 publications identified, 124 duplicates were excluded and 282 were screened based on title and abstract, of which 53 full-text articles were assessed for eligibility. Eighteen articles were included in the systematic review and 13 in the meta-analysis. Only 2 studies assessed tacrolimus levels in SLE pregnancies, while the remainder were in pregnant organ transplant recipients (Figure 1). Tacrolimus levels significantly decreased during pregnancy compared to prepregnancy (SMD -1.05; 95% CI -1.72, -0.37), and significantly increased in the postpartum compared to levels during gestation (SMD 0.87; 95% CI 0.37, 1.37) (Figure 2A,B). Mean differences in tacrolimus trough levels were -1.56 ng/ml (95% CI -2.82, -0.31) between first trimester and before pregnancy, -0.49 ng/ml (95% CI -1.04, -0.07) between second and first trimesters, 0.63 ng/ml (95% CI 0.30, 0.96) between third and second trimesters, and 1.28 ng/ml (95% CI 0.60, 1.96) between the postpartum and third trimester. The variation in tacrolimus levels during pregnancy was usually addressed by increasing the dose during pregnancy vs prepregnancy (MD 1.35 mg/day, 95% CI 0.23, 2.48) and decreasing the dose in the postpartum vs pregnancy (MD -0.92 mg/day; 95% CI -1.8, -0.01) (Figure 2C,D). Figure 1. Flow-chart of study selection. Figure 2. (A) Forest plot of the standardized mean difference between tacrolimus whole blood concentrations during pregnancy (second or third trimester) and before pregnancy. (B) Forest plot of the standardized mean difference between tacrolimus whole blood concentrations in the post-partum and during pregnancy (second or third trimester). (C) Forest plot of the mean difference in mg/day between tacrolimus doses during pregnancy (second or third trimester) and before pregnancy. (D) Forest plot of the mean difference in mg/day between tacrolimus doses in the post-partum and during pregnancy (third trimester). Conclusions Tacrolimus whole-blood levels decrease in the first and second trimesters, then increase back to prepregnancy levels in the postpartum. Tacrolimus dosage in pregnancy is typically increased to maintain tacrolimus trough levels within usual therapeutic ranges. Increasing drug dosage could elevate the bio-effective fraction of tacrolimus (not measured by trough levels), raising concerns for safety and efficacy of dose augmentation during pregnancy. Further research is needed to guide clinicians in adjusting tacrolimus in SLE and non-SLE pregnancies to optimize therapeutic drug monitoring in high-risk populations.
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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 | 0,016 | 0,045 |
| Méta-épidémiologie (sens strict) | 0,003 | 0,002 |
| Méta-épidémiologie (sens large) | 0,022 | 0,045 |
| Bibliométrie | 0,009 | 0,011 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,004 | 0,002 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,003 | 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 ».