A prospective study to compare the efficacy and safety of glucocorticoid-free maintenance therapy versus low-dose glucocorticoid maintenance therapy for lupus nephritis-a pilot, single-center, randomized controlled study.

OBJECTIVE

To prospectively compare the efficacy of glucocorticoid(GC)-free maintenance therapy versus low-dose GC regimens and evaluate short-term safety in complete or partial remission lupus nephritis patients.

METHOD: This study is a prospective, open-label, randomized controlled trial that enrolled lupus nephritis patients who achieved remission within one year prior to screening and maintained stable immunosuppressive therapy. Ninety-three subjects were randomized to a GC-free group (n = 47, tapering off GC over 3 months) and a low-dose GC group (n = 46, prednisone dosage 2.5-10 mg/day), with basic immunosuppressants continued in both groups. Primary endpoints were total flare rate and time to flare, while secondary endpoints included renal or extrarenal flare, immunological changes of parameters, and subgroup analyses stratified by remission status (complete vs. partial) and different maintenance regimen types.

RESULTS

There were 91 patients who were analyzed. The low-dose GC group demonstrated a numerically lower flare rate compared to the GC-free group(4.5%vs. 17.0%, p = 0.065). Among patients experiencing flares, the median time to flare was significantly shorter in the GC-free group (9.4 months) compared with the low-dose group (39.32 months; HR 0.37, 95% CI 0.14-0.99, p = 0.044). Kaplan-Meier analysis revealed significantly higher cumulative flare rates in the GC-free group (log-rank p = 0.031). Notably, the GC-free group exhibited a 14.9% extrarenal flare incidence versus 0% in the low-dose group (absolute risk difference 14.9%, 95% CI 3.2-26.6; p = 0.017).

CONCLUSION

In this pilot study, the flare rate was numerically lower, and the time to flare was significantly longer in the low-dose GC group compared to the GC-free group. These preliminary findings suggest a potential benefit of low-dose GC maintenance therapy but still need large sample size trials to confirm. Key Points • In patients with SLE in remission, glucocorticoid-free therapy significantly increases flare risk and shortens time to flare. • Future biomarker-driven decision-making criteria should be uncovered to replace empirical withdrawal of individual decisions.