Outcomes following immunosuppressive therapy withdrawal after complete renal response in proliferative lupus nephritis

Abstract

Objective: To investigate the rate and factors influencing renal relapse (RR) in proliferative lupus nephritis (LN) patients who discontinued immunosuppressive therapy (IST), as well as the long-term renal outcomes following RR.

Methods: Retrospective, single-centre study of biopsy-confirmed LN patients who had received IST for at least 36 months and maintained complete renal response (CRR) for a minimum of 12 months before therapy discontinuation.

Results: Of a total of 106 patients meeting the inclusion criteria, 76 with proliferative classes were selected for analysis. The median duration of IST prior to discontinuation was 83.5 months (IQR 25th-75th: 53.5-120). Relapse occurred in 29 patients (38.2%) at a median of 26.5 months (IQR 25th-75th: 9.25-63.5 months) following IST withdrawal. Relapses were classified as severe in 9 cases (31%) and moderate in 16 cases (55.2%). Renal rebiopsy was performed in 25 of these patients (86.2%), with 80% retaining the same histological class.Discontinuation of IST at ≤34 years of age significantly increased the risk of RR (adjusted HR: 3.5). In contrast, an IST duration exceeding 48 months prior to discontinuation (HR: 0.26), maintaining CRR for at least 48 months (HR: 0.32), achieving complete remission per DORIS (definition of remission in systemic lupus erythematosus) criteria at IST withdrawal (HR: 0.21) and gradual IST tapering (HR: 0.09) were associated with a reduced risk of RR.Following reintroduction of IST, 20 out of 29 patients (68.9%) achieved CRR, 5 (17.2%) achieved a partial response and 4 (13.8%) did not respond; of these, 3 patients (10.3%) progressed to end-stage renal disease.

Conclusions: Successful withdrawal of IST is possible in carefully selected patients with proliferative LN. If an RR occurs, most patients are able to remain in remission after resuming IST.

Keywords: Lupus Erythematosus, Systemic; Lupus Nephritis; Therapeutics.

Figure 1. Factors influencing renal relapses. *HR: Adjusted by sex, age and renal histological class. AKI, acute renal failure at LN onset; AZA, azathioprine; BR, renal biopsy; CF, cyclophosphamide; CRR, complete renal response; DORIS, definition of remission in systemic lupus erythematosus; HR, hazard ratio; IS, immunosuppressive; LLDAS, lupus low disease activity state; LN, lupus nephritis; MMF, mycophenolate.