Immunosuppressives discontinuation after renal response in lupus nephritis: predictors of flares, time to withdrawal and long-term outcomes

Objectives The optimal duration of immunosuppressive (IS) treatment for lupus nephritis (LN) remains uncertain. We assessed the prevalence and predictors of IS tapering and discontinuation (D/C) in LN patients. Methods Data from 137 inception cohort LN patients were analysed. We examined determinants of flares during tapering and after IS D/C, D/C achievement and time to D/C, and adverse long-term outcomes applying logistic and linear regression models. Results IS tapering was attempted in 111 (81%) patients, and D/C was achieved in 67.5%. Longer time to achieve complete renal response (CR) [odds ratio (OR): 1.07, P = 0.046] and higher SLEDAI-2K at tapering initiation (OR: 2.57, P = 0.008) were correlated with higher risk of renal flares during tapering. Persistent hydroxychloroquine use (>= 2/3 of follow-up) (OR: 0.28, P = 0.08) and lower SLEDAI-2K 12 months before IS D/C (OR: 1.70, P = 0.013) decreased the risk of post-D/C flares. Adverse outcomes (>30% estimated glomerular filtration rate decline, chronic kidney disease, end-stage renal disease, death) at the end of follow-up (median 124 months) were more frequent in patients with flares during IS tapering (53% vs 16%, P < 0.0038) but did not differ between IS D/C achievers and non-achievers. In proliferative LN, differences mirrored those in the entire cohort, except for time to D/C, which occurred 20 months earlier in membranous vs proliferative LN (beta = -19.8, P = 0.014). Conclusion Earlier CR achievement and lower SLEDAI-2K at tapering initiation prevent flares during IS tapering, while persistent hydroxychloroquine use and lower SLEDAI-2K 12 months before IS D/C prevent post-D/C flares. Flares during tapering increase the risk of unfavourable long-term outcomes. Earlier IS D/C is feasible in membranous LN.