Effect Of Belimumab On Pregnancy Outcomes In Patients With Systemic Lupus Erythematosus

Objective:Describe pregnancy outcomes in systemic lupus erythematosus(SLE)patients with use of belimumab,and explore the association exposure to belimumab during pregnancy and adverse pregnancy outcomes(APOs).Methods:Data on adverse pregnancy events,including pregnancy loss(miscarriage or stillbirth),birth defects,perinatal events(pre-eclampsia/preeclampsia,placental abruption,premature rupture of membranes,preterm birth,fetal distress and so on),were collected from clinical trials of belimumab,Belimumab Pregnancy Registry(BPR),and published case reports/series.The exposure time of belimumab,concomitant medications and potential confounding factors of APOs were also described.Results:Of the 228 pregnancies with known outcomes(excluding elective termination),176 were live births.Pregnancy loss,including miscarriage or stillbirth,occurred in 31.8%(n=35/110)of patients who were treated with belimumab in the trials,and birth defects occurred in 5.3%(n=4/75)of the 75 pregnancies ending in live births.In BPR,9.5%(n=6/63)of pregnancies resulted in miscarriage,while 17.5%(n=10/57)of 57 live births had birth defects.Among the case reports/series,10.3%(n=4/39)of pregnancies resulted in miscarriage,while 2.9%(n=1/35)of 35 live births had a birth defect In both the BPR and the case reports/series,the proportion of patients exposed to belimumab in the first trimester was the highest,the former(n=54/55,98.2%)and the latter(n=28/39,71.8%).Except in the third trimester,the proportion of patients exposed to belliumab in the BPR was higher than in the case reports/series.Comparing the incidence of each APOs,except birth defects,patients in the case reports/series had a higher incidence of APOs(including miscarriage,preterm birth,small for gestational age[SGA],and neonatal death)than those in BPR.All pregnant women exposed to belliumab received combination therapy and the information collected from three heterogeneous data sources were filled with confounding factors and/or missing data.Due to the limitations of the data,the patient characteristics throughout pregnancy were only statistically described.Conclusions:This review summarizes limitsed data on pregnancy outcomes in patients with SLE exposed to belimumab.The analysis about the effect of belimumab on pregnancy outcomes in SLE patients was hampered by limitations such as small sample size,confounding factors,absence of data,and lack of a control group.The given data in the whole world are too limited to definitively determine whether belimumab increases the risk ofA POs.In order to evaluate its safety during pregnancy,more clinical experience are available in the future.Background:The data of belimumab therapy in pregnancy are still limited,especially Effect of preconceptional or first-trimester exposure to belimumab on pregnancy.The existing clinical trials did not conduct a control group of which SLE pregnancies had never exposed to belimumab preconceptionally.Confounding factors(including SLE activity during pregnancy,concomitant antiphospholipid syndrome,history of uterine surgery,etc.)interfered with the safety assessment of belimumab use during pregnancy.Objective:To investigate the effect on pregnancy with accidental exposure to belimumab before and/or during the first trimester of pregnancy and to analysis whether the exposure increases the risk of adverse pregnancy events.Methods:To conduct a retrospective cohort study,18 patients with SLE pregnancy during the same period were collected from a single center,of whom 6 were defined as the exposed group(having received at least a infusion of belimumab before conception and/or during the first trimester)and 12 as the control group.All patients,meeting SLICC criteria,were stable at conception and were routinely treated during pregnancy.Demographic and clinical characteristics,obstetric complications and fetal outcomes of the cohort were graphically described.They included risk factors for APOs(adverse pregnancy history,SLE disease activity,SLE clinical manifestations,antinuclear antibody level,concomitant drugs and history of antiphospholipid syndrome,of uterine surgery and of gestational infection),pregnancy outcome,gestational age and neonatal weight,perinatal adverse events,and lupus activity index scores at each stage of pregnancy.Results:A total of 18 pregnancies were collected in this study:6 in the exposed group,including 6 live births and 0 miscarriage;In the control group,there were 12 cases,including 10 live births(83.3%)and 2 abortions(16.7%).There were no significant differences in the risk factors of APOs between the two groups,including age,body weight course of disease,adverse pregnancy history,history of antiphospholipid syndrome,history of uterine surgery,history of infection during pregnancy,and accompanying drugs.SLEDAI,urine abnormalities,C-reactive protein(CRP),erythrocyte sedimentation(ESR),complement 3(C3),complement 4(C4),anti ds-DNA antibody and anti-ENA antibody were compared between the two groups at 5 observation time points,including 6 months before pregnancy,first trimester,second trimester,third trimester and 6 months postpartum.There was no statistical difference between the two groups.Patients in the two groups were matched with a 1:1 propensity score.After 6 patients were successfully matched the incidence of adverse pregnancy outcomes(APOs)and perinatal adverse pregnancy events(APEs)were compared between the two groups.Before and after matching,there was no significant difference in the incidence of APOs and APEs between the two groups.Conclusions:Our study provides new clinical evidence for the application of belimumab in SLE pregnant patients.Given that global data are still limited to definitively determine whether belimumab increases the risk of adverse pregnancy outcomes,more clinical high-quality data needs to be accumulated to evaluate its safety during pregnancy.