Navigating the therapeutic landscape: Biologics and immunosuppressive therapy in lupus nephritis during pregnancy

Abstract

Background

Lupus nephritis (LN) predominantly affects women of reproductive age and carries substantial risks during pregnancy, including disease flare, preeclampsia, acute kidney injury, and adverse fetal outcomes. The therapeutic armamentarium for LN has expanded considerably with the approval of voclosporin, belimumab, and obinutuzumab, yet pregnancy safety data for these agents remain conspicuously absent. Concurrently, the 2024 EULAR recommendations for antirheumatic drugs in reproduction, the 2025 EULAR lupus nephritis update, and the 2024 KDIGO guidelines have reset the landscape of management guidance. This review critically appraises the evidence on the safety and clinical use of all current LN-relevant immunosuppressive and biologic therapies during pregnancy, lactation, and the periconceptional period.

Methods

A comprehensive narrative review of literature published between January 2000 and May 2025 was conducted using PubMed, MEDLINE, EMBASE, and Cochrane databases. Key guidelines, pregnancy registries, and landmark clinical trial data were incorporated.

Results

Hydroxychloroquine and azathioprine remain the cornerstones of pregnancy-compatible LN management. Tacrolimus is an acceptable calcineurin inhibitor with appropriate therapeutic drug monitoring. Low-dose aspirin is recommended universally to reduce preeclampsia risk. Mycophenolate mofetil is teratogenic and absolutely contraindicated in the first trimester. Voclosporin and obinutuzumab lack any pregnancy safety data and should be avoided. Belimumab data from the pregnancy registry have not raised major signals; selective use may be considered in refractory cases. Rituximab may be used cautiously for life-threatening disease, avoiding the third trimester due to neonatal B-cell depletion. Anifrolumab has no pregnancy data and should be reserved for situations where no compatible alternative exists.

Conclusion

The growing number of effective LN therapies creates both opportunities and new dilemmas in pregnancy management. A structured, phase-based approach to drug selection — anchored in preconception counselling, timely medication switches, and multidisciplinary surveillance — is essential to optimise maternal and fetal outcomes. Dedicated pregnancy registries for novel biologics are urgently needed.