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Abstract
Background Tacrolimus is one of the major treatment options for systemic lupus erythematosus (SLE) and considered pregnancy-compatible medication. Since little is known about tacrolimus safety during pregnancy complicated by SLE, this study was designed.
Methods We included SLE pregnant patients who were followed up at two Japanese tertiary referral centers. We performed multivariate logistic regression analysis to assess each adverse pregnancy outcome (APO) risk. Moreover, we assessed the influence of tacrolimus on the APO ratio in pregnant with lupus nephritis, and the impact of combined tacrolimus-aspirin therapy on the APO ratio relative to patients exclusively administered tacrolimus.
Results Of the 124 pregnancies, 29 were exposed to tacrolimus. Multivariate analysis showed no statistical difference in APO ratio. (overall APO: adjusted odds ratio [aOR], 0.69; 95% confidence interval [CI], 0.23–2.03; p=0.50; maternal APO: aOR, 1.17; 95% CI, 0.36–3.83; p=0.80; neonatal APO: aOR, 1.10; 95% CI, 0.38–3.21; p=0.86; PROISSE APO: aOR, 0.50; 95% CI, 0.14–1.74; p=0.27) (table 1).
Blood pressure and estimated glomerular filtration rate (eGFR) during pregnancy and after delivery did not differ between the two groups. Receiver operating characteristic (ROC) curve showed that tacrolimus concentration>2.6ng/ml was related to reduced preterm birth rate. (AUC=0.85, 95% CI: 0.61–1.00, sensitivity: 93% and specificity: 75%) (figure 1).
Regarding tacrolimus effect on lupus nephritis pregnancy, tacrolimus showed no increased risk of APO, blood pressure or eGFR during pregnancy and after delivery. (overall APO: OR, 1.00; 95% CI, 0.25–4.08; p=0.98; maternal APO: OR 1.60, 95% CI, 0.39–6.64; p=0.51; neonatal APO: OR, 0.71; 95% CI, 0.17–3.03; p=0.65, PROMISSE APO: OR, 0.50; 95% CI, 0.08–3.22; p=0.47). (table 2).
Tacrolimus-aspirin combination therapy showed protective tendency against hypertensive disorders during pregnancy, preeclampsia and low birth weight.
Conclusions Tacrolimus use during lupus pregnancy showed no significant influence on APO, blood pressure, or renal function, suggesting that tacrolimus might be a suitable option for controlling lupus activity during pregnancy. In addition, when using tacrolimus during pregnancy, we should aim its trough concentration ≥2.6 ng/ml while paying careful attention to possible maternal side effects of tacrolimus.
Prevalence of adverse pregnancy outcome according to tacrolimus exposure
Prevalence of adverse pregnancy outcome in patients with lupus nephritis according to the tacrolimus exposure
ROC curve for the maximum tacrolimus trough concentration during pregnancy and each adverse pregnancy outcome. APO: adverse pregnancy outcome, AUC: are under the curve. CI: confidence interval HDP: hypertensive disorders during pregnancy. ROC: receiver operating characteristic, SGA: small for gestational age
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