Immunosuppressive therapy withdrawal in lupus nephritis, is it possible? A systematic review

Introduction: Maintenance of immunosuppressants (IST) is critical for sustaining remission in lupus nephritis (LN) patients. However, long-term use is associated with an increased risk of side effects such as infection. Yet, early IST withdrawal also poses a high risk of flare. This study aims to provide an overview of the impact of optimal IST withdrawal in patients with LN who have achieved remission. Method: We conducted a systematic review of randomized controlled trials (RCTs) and observational studies regarding the discontinuation of IST in patients with proliferative LN who had been in remission for at least 1 year. Data from PubMed, ProQuest, and Web of Science were extracted on patient demographics, baseline characteristics, treatment regimens, and outcomes, including flare rates, renal function, and biopsy findings. The risk of bias was assessed using the Newcastle-Ottawa Scale and the JADAD Score. Results: Five studies with 310 patients were included. The mean age of participants ranged from 26 to 38 years. Overall, flares following IST withdrawal occurred in an average of 28.7% of patients. Between the two groups (flare and no-flare), baseline serum creatinine was comparable, but baseline proteinuria and C3 & C4 levels were varied across studies. The duration of lupus before study entry was approximately 4-10 years, with a duration of complete remission of 12-59.5 months before IST withdrawal. Follow-up periods ranged from 24 to 215 months. The Biopsy Activity Index and Chronicity Index at baseline also showed variation but generally indicated a higher level of chronic damage in the flare group. Discussion: Discontinuation of IST is feasible but may be associated with an increased risk of severe flares, often requiring reintroduction of induction therapy. Careful assessment and monitoring of both histologic and clinical activity are essential when evaluating remission and considering IST withdrawal, as a low activity index may guide safer withdrawal strategies. Conclusion: IST withdrawal is feasible in patients with LN who have achieved remission, but careful monitoring is required due to the risk of relapse and potential progression of chronic kidney damage. Histological confirmation and predictive tools may support safer withdrawal decisions.