Antibodies | Clinical Decision-Making for Belimumab Use in Pregnancy with Systemic Lupus Erythematosus: A Case Analysis of Three Consecutive Pregnancies

This study provides critical clinical reference for individualized management of BEL use during pregnancy in patients with active SLE, suggesting that maintenance therapy may help control disease activity in high-risk patients, though potential perinatal risks must be carefully weighed.

 

Literature Overview

The article, 'Monoclonal Antibodies in Pregnancy of Patients with Systemic Lupus Erythematosus: Friend or Foe? A Case Report of a Patient with Multiple Pregnancies,' published in the journal Antibodies, systematically investigates the use of belimumab (BEL) across three consecutive pregnancies in a patient with systemic lupus erythematosus (SLE) and its impact on maternal and fetal outcomes. By longitudinally comparing BEL exposure strategies across different pregnancies in the same patient, the study reveals a potential association between maintenance therapy and disease activity control. The article emphasizes the importance of individualized and shared decision-making in the absence of large-scale randomized controlled trials.

Background Knowledge

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease primarily affecting women of childbearing age. Disease activity during pregnancy significantly increases the risk of maternal and fetal complications, including preeclampsia, preterm birth, and fetal growth restriction. Although drugs such as HCQ, AZA, and CYA are widely considered relatively safe during pregnancy, they may be insufficient to maintain disease stability in patients with high disease activity or organ involvement. Belimumab (BEL), an IgG1λ monoclonal antibody targeting B-lymphocyte stimulator (BAFF), has become an important biologic agent for treating active SLE. However, its use was previously limited due to a lack of early pregnancy safety data. In recent years, with accumulating real-world evidence from registries such as the Belimumab Pregnancy Registry (BPR), the use of BEL in specific scenarios has gradually been incorporated into guidelines, such as the 2024 updated EULAR recommendations. The current research challenge lies in balancing maternal disease control against potential fetal exposure risks, especially given the established placental transfer mechanism (via FcRn receptors). This study's strength lies in its use of longitudinal data from three pregnancies in the same patient, enabling a within-subject controlled analysis that reduces confounding from inter-individual variability and allows deeper exploration of the clinical consequences of interrupting versus maintaining BEL therapy.

 

 

Research Methods and Experiments

The authors employed a retrospective case report design, detailing three consecutive live births in an African American woman with SLE between 2019 and 2024. The study constructed a complete clinical trajectory by longitudinally recording disease activity (SLEDAI-2K, CLASI-A), laboratory markers (complement, anti-dsDNA), treatment regimens (including BEL, HCQ, PDN, CYA), and maternal-fetal outcomes for each pregnancy. Key evidence came from comparing BEL use strategies across different gestational periods: BEL was discontinued immediately upon pregnancy confirmation during the first pregnancy, but continued until week 20 of gestation in the second and third pregnancies. The clinical impact of these differing strategies was assessed by analyzing the timing and severity of disease flares, alongside fetal growth, Apgar scores, and neonatal infection outcomes. Additionally, long-term follow-up data—including child growth and vaccine response—were included to evaluate potential long-term safety.

Key Conclusions and Perspectives

• Late-pregnancy and postpartum disease flares occurred after discontinuing BEL in the first pregnancy, suggesting that treatment interruption may increase the risk of disease reactivation, providing guidance for the design of subsequent clinical monitoring strategies
• Continuing BEL until week 20 of gestation in the second and third pregnancies, while not completely preventing late flares, resulted in relatively better disease control, supporting the consideration of sustained therapy into mid-pregnancy for high-risk SLE patients and providing a basis for optimizing gestational drug regimens in drug development
• All newborns showed no congenital malformations, placental insufficiency, or intrauterine growth restriction, and children exhibited normal long-term development, indicating that BEL exposure did not result in apparent short- or long-term structural or functional abnormalities, enhancing confidence in safety assessments of biologics in disease modeling
• The newborn in the third pregnancy developed early-onset sepsis and meningitis, but multiple confounding factors were present (high disease activity, PDN, CYA), making it impossible to attribute this to BEL, highlighting the need for future studies to more precisely control for confounders to clarify target safety
• Based on pharmacokinetics, discontinuing BEL at week 20 may limit late fetal exposure but may be insufficient to maintain maternal homeostasis, suggesting future research should explore individualized discontinuation timing to guide more precise definition of exposure windows in experimental design

Research Significance and Prospects

This study provides valuable real-world evidence for clinical decision-making regarding biologic use during pregnancy in SLE patients. It underscores the necessity of shifting from a one-size-fits-all discontinuation approach to individualized, risk-adapted strategies, especially in patients at high recurrence risk. Future guidelines should integrate such longitudinal case data to promote the application of shared decision-making models. For drug development, prospective cohort studies are needed to clarify the pharmacokinetic/pharmacodynamic profiles of BEL across different trimesters and to explore biomarker-guided treatment strategies.

 

 

Conclusion

This study, through an in-depth analysis of three pregnancies in the same SLE patient, provides key evidence for the individualized management of belimumab (BEL) during pregnancy. Although limited by small sample size and potential confounders, the findings suggest that maintaining BEL into mid-pregnancy may help improve maternal disease control in high-risk patients, with no observed major fetal structural abnormalities or developmental impairments. This supports including BEL as a treatment option for active SLE during pregnancy, especially when conventional therapies fail to achieve adequate control. However, disease flares may still occur, and neonatal infection risks warrant vigilance, emphasizing the importance of multidisciplinary collaboration and close monitoring. Future research should expand sample sizes and incorporate pharmacokinetic data to establish more precise risk-benefit assessment models. From bench to bedside, this study lays the foundation for optimizing SLE pregnancy care pathways, advancing the transition from empirical management to individualized, mechanism-driven precision therapy, ultimately improving maternal and infant outcomes.

 

Chiara Orlandi, Angela Tincani, Micaela Fredi, Franco Franceschini, and Ilaria Cavazzana. Monoclonal Antibodies in Pregnancy of Patients with Systemic Lupus Erythematosus: Friend or Foe? A Case Report of a Patient with Multiple Pregnancies. Antibodies.