A prospective multicenter randomized controlled trial pre-emptive increase in immunosuppression for asymptomatic serological reactivation in patients with lupus nephritis in clinical remission.

Abstract

The management of patients with lupus nephritis (LN) in clinical remission who demonstrate asymptomatic serological reactivation remains uncertain. Results from our previous study suggested that a pre-emptive moderate increase of immunosuppressive treatment might reduce disease flares. Here, we conducted a prospective multicenter randomized controlled trial to compare pre-emptive treatment (PT) against observant management (Control) in clinically stable patients with LN and asymptomatic serological reactivation who were receiving low-dose glucocorticoid and mycophenolate or azathioprine as maintenance immunosuppression. PT included an increase in prednisolone dose from ≤5 mg/d to 0.4-0.5 mg/kg/d and an increase in mycophenolate or azathioprine dose to 1.5 g/d and 100 mg/d, respectively, followed by tapering of prednisolone dose to the original level by 12 weeks. Patients were followed for 24 months from randomization. The primary outcome was 24-month survival free of kidney flares. Secondary outcomes included survival free of extra-kidney flares, change in kidney and immunological parameters, and adverse events. Forty-nine patients were randomized (24 PT and 25 Control). No kidney flare occurred in PT while five kidney flares occurred at 6.0 (interquartile range: 3.0-10.0) months in Controls. PT patients had superior 24-month survival free of kidney, extra-kidney, and overall flares than Controls (100% vs. 80%, 91% vs. 72%, and 91% vs. 52%, respectively, significant for all). PT patients showed improved anti-dsDNA and C3 compared to baseline, but not patients in the Control arm. Adverse events were few and similar, and kidney function remained stable in both groups. A pre-emptive moderate increase of immunosuppression was effective in preventing kidney flares in patients with LN and with asymptomatic serological reactivation and was well tolerated. Registered at ClinicalTrials.gov with study number XXX.