Safety of tacrolimus use during pregnancy and related pregnancy outcomes in patients with systemic lupus erythematosus: A retrospective single-center analysis in Japan

Objective Tacrolimus is one of the drugs that can be used in pregnancies complicated with systemic lupus erythematosus (SLE), but there are still few reports on its pregnancy outcomes. Although tacrolimus has been reported to cause adverse events, such as increased blood pressure, abnormal glucose metabolism, and susceptibility to infection, there have been no studies on the impact of tacrolimus in SLE pregnancies at these points. We performed a retrospective observational study of pregnancies complicated by SLE at St Luke's International Hospital in Tokyo from April 2003 to August 2021. Methods Basic clinical information on SLE, pregnancy outcomes, disease activity before and after pregnancy, laboratory results, blood pressure, blood glucose levels, treatment regimens, and presence of infection was extracted from electronic medical records. We defined overall adverse pregnancy outcomes (APOs) as follows: (1) fetal death after 10 gestational weeks, (2) preterm delivery, (3) delivery due to hypertensive disorders of pregnancy, preeclampsia, or placental insufficiency, or (4) the diagnosis of small for gestational age infants. We also examined whether there was a statistical difference in APO incidence between patients treated with and without tacrolimus. Results Pregnancy outcomes were obtained for 48 patients with a total of 60 pregnancies complicated by SLE. In 20 (33.3%) of these pregnancies, the patients took tacrolimus, and 28 (46.7%) of the pregnancies had APOs. APO incidence did not statistically differ between the tacrolimus and non-tacrolimus groups in the multivariate analysis (p = 1.00, adjusted OR 1, 95% CI: 0.23-4.39). Multiple regression analyses indicated that tacrolimus use did not significantly affect systolic blood pressure in the third trimester (B = -2.23, p = .74) or blood glucose levels in the first trimester (B = 10.2, p = .056). Incidence of infections did not significantly differ between patients treated with and without tacrolimus in the univariate analysis (10.8% vs. 21.1%, p = .42). Conclusion Tacrolimus did not significantly affect pregnancy outcomes, blood pressure, or glucose levels. Further research is required to confirm its effects in a larger population.