In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.

Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.

Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.

Background Since systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern. Objective To identify predictors of adverse pregnancy outcome (APO) in inactive or stable active SLE patients Design Prospective Cohort Setting Multicenter Patients 385 patients (49% non-Hispanic White; 31% prior nephritis) with SLE in PROMISSE. Exclusion criteria were: proteinuria >1000 mg/24 hour, creatinine >1.2 mg/dL, prednisone >20 mg/day, or multi-fetal pregnancy. Measurements APO included: fetal/neonatal death; birth <36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small for gestational age (SGA) <5%. Disease activity was assessed by SLEPDAI and physician's global assessment (PGA). Results APO occurred in 19.0% (95% CI: 15.2% - 23.2%) of pregnancies, fetal death (4%), neonatal death (1%), preterm delivery (9%), and SGA (10%). Severe flares in the second and third trimester occurred in 2.5% and 3.0%, respectively. Baseline predictors of APO included lupus anticoagulant positive (OR = 8.32, 95% CI: 3.59-19.26), antihypertensive use (OR = 7.05, 95% CI: 3.05 - 16.31), PGA>1 (OR = 4.02, 95% CI: 1.84 - 8.82) and platelets (OR = 1.33 per 50K decrease, 95% CI:1.09-1.63); non-Hispanic White was protective (OR = 0.45, 95% CI: 0.24-0.84). Maternal flares, higher disease activity, and smaller increase in C3 later in pregnancy also predicted APO. Among women without baseline risk factors, the APO rate was 7.8%. For those either LAC positive, or LAC negative but non-White or Hispanic and taking antihypertensives, APO rate was 58%; fetal/neonatal mortality 22%. Limitations Excluded patients with high disease activity. Conclusions In pregnant SLE patients with inactive or stable mild/moderate disease, severe flares are infrequent, and absent specific risk factors, outcomes are favorable. Primary Funding Source National Institutes of Health

Background Cardiac manifestations of neonatal lupus (cardiac-NL) include conduction disease and rarely an isolated cardiomyopathy. This study was initiated to determine the mortality and morbidity of cardiac-NL and associated risk factors in a multi-racial/ethnic US-based registry to provide insights into the pathogenesis of antibody mediated injury and data for counseling. Methods and Results Three hundred and twenty-five offspring exposed to maternal anti-SSA/Ro antibodies with cardiac-NL met entry criteria. Maternal, fetal echocardiographic, and neonatal risk factors were assessed for association with mortality. Fifty-seven (17.5%) died; 30% in utero. The probability of in utero death was 6%. The cumulative probability of survival at 10 years for a child born alive was 86%. Fetal echocardiographic risk factors associated with increased mortality in a multivariable analysis of all cases included hydrops and endocardial fibroelastosis (EFE). Significant predictors of in utero death were hydrops and earlier diagnosis, and for postnatal death, hydrops, EFE, and lower ventricular rate. Isolated heart block was associated with a 7.8% case fatality rate whereas the concomitant presence of dilated cardiomyopathy or EFE quadrupled the case fatality rate. There was a significantly higher case fatality rate in minorities compared to Caucasians, who were at a lower risk of hydrops and EFE. Pacing was required in 70% and cardiac transplantation in four children. Conclusion Nearly one-fifth of fetuses who develop cardiac-NL die from complications which are predicted by echocardiographic abnormalities consistent with antibody associated disease beyond the AV node. The disparity in outcomes observed between minorities and Caucasians warrants further investigation.

Background A recent case control study suggested a benefit of hydroxychloroquine (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac-NL) in pregnancies of anti-SSA/Ro positive patients with Systemic Lupus Erythematosus (SLE). A historical cohort assembled from three international databases was used to evaluate whether HCQ reduces the nearly tenfold increase in risk of recurrence of cardiac-NL, independent of maternal health status. Methods and Results Two hundred fifty seven pregnancies of anti-SSA/Ro positive mothers (40 exposed and 217 unexposed to HCQ) subsequent to the birth of a child with cardiac-NL were identified from three databases (U.S., England, and France). Exposure was defined as the sustained use of HCQ throughout pregnancy with initiation prior to ten weeks of gestation. The recurrence rate of cardiac-NL in fetuses exposed to HCQ was 7.5% (3/40) compared to 21.2% (46/217) in the unexposed group (p=0.050). While there were no deaths in the exposed group, the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 22%. In a multivariable analysis which adjusted for database source, maternal race/ethnicity, and anti-SSB/La status, HCQ use remained significantly associated with a decreased risk of cardiac-NL (Odds Ratio=0.23; 95% CI: 0.06–0.92; p=0.037). Similar results were obtained with propensity score analysis, an alternative approach to adjust for possible confounding by indication. Conclusions Based on aggregate data from a multinational effort, in mothers at high risk of having a child with cardiac-NL, the use of HCQ may protect against recurrence of disease in a subsequent pregnancy.

Objective To evaluate seroreactivity and disease flares after COVID‐19 vaccination in a multi‐ethnic/racial cohort of patients with systemic lupus erythematosus (SLE). Methods 90 SLE patients and 20 healthy controls receiving a complete COVID‐19 vaccine regimen were included. IgG seroreactivity to the SARS‐CoV‐2 spike receptor‐binding domain (RBD) and SARS‐CoV‐2 microneutralization were used to evaluate B cell responses; IFN‐γ production to assess T cell responses was measured by ELISpot. Disease activity was measured by the hybrid SLE disease activity index (SLEDAI) and flares were assigned by the SELENA/SLEDAI flare index. Results Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS‐CoV‐2 spike RBD than controls. Twenty‐six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti‐dsDNA level prior to vaccination associated with decreased vaccine responses. IgG seroreactivity to the SARS‐CoV‐2 Spike RBD strongly correlated with the SARS‐CoV‐2 microneutralization titers and antigen‐specific IFN‐γ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN‐γ production was likewise diminished. Pre‐/post‐vaccination SLEDAI scores were similar. Only 11.4% of patients had a post‐vaccination flare; 1.3% were severe. Conclusion In a multi‐ethnic/racial study of SLE patients 29% had a low response to the COVID‐19 vaccine which was associated with being on immunosuppression. Reassuringly, disease flares were rare. While minimal protective levels remain unknown, these data suggest protocol development is needed to assess efficacy of booster vaccination.

Background-Anti-SSA/Ro-associated third-degree congenital heart block is irreversible, prompting a search for early markers and effective therapy. Methods and Results-One hundred twenty-seven pregnant women with anti-SSA/Ro antibodies were enrolled; 95 completed an evaluable course in 98 pregnancies. The protocol included fetal echocardiograms performed weekly from 16 to 26 weeks' gestation and biweekly from 26 to 34 weeks. PR intervals Ͼ150 ms were considered prolonged, consistent with first-degree block. Ninety-two fetuses had normal PR intervals. Neonatal lupus developed in 10 cases; 4 were neonatal lupus rash only. Three fetuses had third-degree block; none had a preceding abnormal PR interval, although in 2 fetuses Ͼ1 week elapsed between echocardiographic evaluations. Tricuspid regurgitation preceded third-degree block in 1 fetus, and an atrial echodensity preceded block in a second. Two fetuses had PR intervals Ͼ150 ms. Both were detected at or before 22 weeks, and each reversed within 1 week with 4 mg dexamethasone. The ECG of 1 additional newborn revealed a prolonged PR interval persistent at 3 years despite normal intervals throughout gestation. No first-degree block developed after a normal ECG at birth. Heart block occurred in 3 of 16 pregnancies (19%) in mothers with a previous child with congenital heart block and in 3 of 74 pregnancies (4%) in mothers without a previous child with congenital heart block or rash (Pϭ0.067). Conclusions-Prolongation of the PR interval was uncommon and did not precede more advanced block. There was a trend toward more congenital heart block in fetuses of women with previously affected offspring than those without previously affected offspring. Advanced block and cardiomyopathy can occur within 1 week of a normal echocardiogram without initial first-degree block. Echodensities and moderate/severe tricuspid regurgitation merit attention as early signs of injury. (Circulation. 2008;117:485-493.)