Patients with lupus nephritis who discontinued immunosuppressive therapy after maintaining complete renal response for at least 48 months had a lower risk of relapse, whereas those aged 34 years or younger faced more than a threefold increased risk, according to a recent study.
In a retrospective, single-center study, published in Lupus Science & Medicine, researchers assessed renal relapse (RR) rates and predictive factors following the withdrawal of immunosuppressive therapy (IST) in patients with proliferative lupus nephritis (LN) who had achieved a sustained complete renal response (CRR). Led by Paola Vidal-Montal of the Department of Rheumatology, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain, they analyzed 76 patients with biopsy-confirmed proliferative LN (classes III, IV, or mixed III/IV+V) who had received IST for at least 36 months and maintained CRR for a minimum of 12 months prior to therapy discontinuation. The median IST duration before discontinuation was 83.5 months (interquartile range [IQR] = 53.5–120).
Renal relapse occurred in 29 of 76 patients (38.2%) at a median of 26.5 months (IQR = 9.25–63.5) following IST withdrawal. Among those with RR, nine patients (31%) experienced severe relapses, 16 (55.2%) had moderate relapses, and four (13.8%) had mild relapses. Renal biopsy was performed in 25 of the 29 relapsed patients (86.2%), while 20 (80%) maintained the same histological class.
Cox regression analysis identified factors associated with a reduced risk of RR. An IST duration of more than 48 months before discontinuation was protective (HR = 0.31, 95% CI = 0.14–0.69), as was maintaining CRR for at least 48 months (HR = 0.33, 95% CI = 0.14–0.81). Achieving complete remission per DORIS criteria at IST withdrawal significantly reduced RR risk (HR = 0.24, 95% CI = 0.10–0.63), as did gradual IST tapering (HR = 0.29, 95% CI = 0.13–0.64). Conversely, patients aged 34 years or younger at the time of IST withdrawal had a significantly increased risk of RR (adjusted HR = 3.65, 95% CI = 1.28–10.42).
Following IST reintroduction, 20 of 29 relapsed patients (68.9%) achieved CRR, five (17.2%) attained a partial response, four (13.8%) did not respond, and three (10.3%) progressed to end-stage renal disease. In contrast, patients who remained in remission without relapse had a median follow-up of 113.5 months (IQR = 65–131.3) post-IST withdrawal.
IST withdrawal may be possible in select patients with proliferative LN who maintain CRR for extended durations, meet remission criteria, and undergo gradual tapering; however, relapse remains a significant risk, particularly in younger patients. Progression also remains a concern for a subset of patients. These results provide clinically relevant insights for optimizing IST withdrawal strategies in LN management.
No disclosures are listed in the published study.