OP0280 WEANING OF MAINTENANCE IMMUNOSUPPRESSIVE THERAPY IN LUPUS NEPHRITIS (WIN-Lupus): A MULTICENTER RANDOMIZED CONTROLLED TRIAL

BackgroundLupus 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.ObjectivesThe WIN-Lupus trial tested whether IST discontinuation after 2-3 years in proliferative LN was non-inferior to IST continuation for 2 more years.MethodsWIN-Lupus is an investigator-initiated academic randomized controlled trial, conducted in 28 French centers. Patients on maintenance IST with azathioprine or mycophenolate mofetil for a minimum of 2 years and a maximum of 3 years, and who were taking Hydroxychloroquine, were randomized (1:1) between 2 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.ResultsBetween 2011 and 2016, 125 patients were screened and 96 were randomized in the trial: 48 in the IST continuation group, 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]). Non-inferiority was not demonstrated for relapse rate. Time to renal relapse did not differ between groups (p=0.092). Severe SLE flares (renal or extra-renal) were less frequent in patients with IST continuation compared to IST discontinuation (5/40 vs 14/44 patients, p=0.035). IST discontinuation was associated with lower health-related costs. Adverse events did not differ between groups.ConclusionNon-inferiority 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.References[1]Moroni G et al. When and how is it possible to stop therapy in patients with lupus nephritis? Clin J Am Soc Nephrol. 2021. CJN.04830421. doi: 10.2215/CJN.04830421.[2]Fanouriakis A et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79(6):713-723.[3]Jourde-Chiche N et al. Proliferative lupus nephritis treatment: practice survey in nephrology and internal medicine in France. Nephrol Ther. 2014;10(3):170-6.[4]Zen M et al. Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis. Rheumatology (Oxford). 2021;keab373. doi: 10.1093/rheumatology/keab373.[5]Malvar A et al. Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis. Kidney Int. 2020;97(1):156-162.AcknowledgementsGroupe Coopératif sur le Lupus Rénal (GCLR)Disclosure of InterestsNoemie JOURDE-CHICHE Speakers bureau: Vifor Pharma, Grant/research support from: Fresenius Medical Care: grant paid to my institution (AP-HM) for the CINEVAS study in ANCA-associated vasculitis, Nathalie Costedoat-Chalumeau Grant/research support from: AP-HP received a research support from ROCHE for the OBILUP trial, Karine Baumstarck: None declared, LAURENCE BOUILLET Speakers bureau: GSK, novartis, biocryst, takeda, behring, Paid instructor for: takeda, novartis, Consultant of: GSK, novartis, biocryst, takeda, behring, blueprint, Grant/research support from: takeda, gsk, sanofi, biocryst, novartis, Stéphane Burtey: None declared, Valerie Caudwell: None declared, Laurent Chiche Speakers bureau: BMS, Paid instructor for: BMS, Lionel Couzi Speakers bureau: Astellas, Chiesi, Novartis, Sandoz, Ostuka, GSK, Biotest, Consultant of: Biotest, Hansa, Novartis, Grant/research support from: Novartis, Astellas, Christophe DELIGNY: None declared, Bertrand Dussol Speakers bureau: Genzyme, Novonordisk, Grant/research support from: Shire, Stanislas Faguer Speakers bureau: Asahi, Vifor Pharma, Sanofi, Consultant of: Abyonyx Pharma, Pierre Gobert: None declared, Guillaume Gondran Speakers bureau: Pfizer, Novartis, Consultant of: Genzyme, Antoine Huart Speakers bureau: Janssen, Paid instructor for: Pfizer, Aurélie Hummel: None declared, Emilie Kalbacher: None declared, Alexandre Karras Speakers bureau: Vifor, GSK, Astra-Zeneca, Roche, Paid instructor for: Vifor, Sanofi, Alexion, Consultant of: Novartis, GSK, Bohringer-Ingelheim, Marc Lambert Speakers bureau: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Paid instructor for: CHUGAI-ROCHE, Consultant of: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Grant/research support from: CHUGAI-ROCHE, Véronique LE GUERN: None declared, Sandrine Loubiere: None declared, Helene Maillard: None declared, Francois Maurier: None declared, Micheline Pha: None declared, Viviane Queyrel Paid instructor for: GSK, Consultant of: Boehringer Ingelheim, Francoise Sarrot-Reynauld: None declared, David Verhelst: None declared, Eric Hachulla Speakers bureau: Johnson & Johnson, GSK, Roche-Chugai, Consultant of: Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, Grant/research support from: CSL Behring, GSK, Roche-Chugai and Johnson & Johnson, Zahir Amoura Speakers bureau: GSK, CSL Behring, Consultant of: GSK, Grant/research support from: GSK, Eric Daugas Speakers bureau: GSK, Amgen, Paid instructor for: GSK, Astra Zeneca, Consultant of: GSK, Astra Zeneca, Amgen, Grant/research support from: ROCHE for the OBILUP trial (AP-HP)