Variations in Tacrolimus Whole Blood Concentrations During Pregnancy and Its Implications for Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis
Notice bibliographique
Résumé
Objectives Tacrolimus is a pregnancy-compatible immunosuppressive increasingly used in systemic lupus erythematosus (SLE) pregnancies. Physiological changes throughout pregnancy alters the whole blood concentrations of tacrolimus 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. Random-effects models were used to estimate standardized mean differences (SMD) or mean differences (MD), with 95% confidence intervals (CI) of tacrolimus trough levels and doses before, during and after pregnancy. Results Of 404 publications identified, 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. Tacrolimus levels significantly decreased during pregnancy compared to pre-pregnancy (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 1). 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 trimesters. The variation in tacrolimus levels during pregnancy was usually addressed by increasing the dose during pregnancy vs pre-pregnancy (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 1). Figure 1. (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). Conclusion Tacrolimus blood levels decrease during the first and second trimesters, then return to pre-pregnancy levels in the postpartum. Pregnancy often requires increased tacrolimus doses to keep trough levels within therapeutic ranges. Higher dosages might increase the bio-effective tacrolimus fraction, raising safety concerns about dose augmentation during pregnancy. More research is necessary to help clinicians adjust tacrolimus in SLE and non-SLE pregnancies to ensure optimal therapeutic drug monitoring in high-risk groups.
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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 | 0,013 | 0,038 |
| Méta-épidémiologie (sens strict) | 0,003 | 0,002 |
| Méta-épidémiologie (sens large) | 0,021 | 0,042 |
| Bibliométrie | 0,008 | 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 | 0,002 | 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 ».