FC053: Weaning of Maintenance Immunosuppressive Therapy in Lupus Nephritis (Win-Lupus): A multicenter randomized controlled trial

Abstract BACKGROUND AND AIMS Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with an induction immunosuppressive therapy (IST), followed by a maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST for proliferative LN is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2–3 years in proliferative LN was non-inferior to IST continuation for 2 more years. METHOD WIN-Lupus is an investigator-initiated academic randomized controlled trial, conducted in 28 French centres. Patients on maintenance IST with azathioprine or mycophenolate mofetil for a minimum of 2 years and a maximum of 3 years, and those who were taking hydroxychloroquine were randomized (1:1) between two groups: IST continuation and IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events, kidney function, disease activity, corticosteroid exposure, patient-reported outcome and medico-economic impact. RESULTS Between 2011 and 2016, 125 patients were screened and 96 were randomized in the trial: 48 in the IST continuation group and 48 in the IST discontinuation group. In the per-protocol population, a relapse of proliferative LN occurred in 5/40 (10.4%) patients with IST continuation, and in 12/44 (25%) patients with IST discontinuation (difference 14.8%, 95% CI [−1.9; 31.5]). Noninferiority was not demonstrated for relapse rate. Time to renal relapse did not differ between groups (P = 0.092). Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation compared to IST discontinuation (5/40 versus 14/44 patients; P = 0.035). IST discontinuation was associated with lower health-related costs. Adverse events did not differ between groups. CONCLUSION Noninferiority of maintenance IST discontinuation after 2 to 3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flare.