Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial

OBJECTIVES: Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance I...

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Autores principales: Jourde-Chiche, Noemie, Costedoat-Chalumeau, Nathalie, Baumstarck, Karine, Loundou, Anderson, Bouillet, Laurence, Burtey, Stéphane, Caudwell, Valérie, Chiche, Laurent, Couzi, Lionel, Daniel, Laurent, Deligny, Christophe, Dussol, Bertrand, Faguer, Stanislas, Gobert, Pierre, Gondran, Guillaume, Huart, Antoine, Hummel, Aurélie, Kalbacher, Emilie, Karras, Adexandre, Lambert, Marc, Le Guern, Véronique, Lebourg, Ludivine, Loubière, Sandrine, Maillard-Lefebvre, Hélène, Maurier, François, Pha, Micheline, Queyrel, Viviane, Remy, Philippe, Sarrot-Reynauld, Françoise, Verhelst, David, Hachulla, Eric, Amoura, Zahir, Daugas, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484365/
https://www.ncbi.nlm.nih.gov/pubmed/35725295
http://dx.doi.org/10.1136/annrheumdis-2022-222435
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author Jourde-Chiche, Noemie
Costedoat-Chalumeau, Nathalie
Baumstarck, Karine
Loundou, Anderson
Bouillet, Laurence
Burtey, Stéphane
Caudwell, Valérie
Chiche, Laurent
Couzi, Lionel
Daniel, Laurent
Deligny, Christophe
Dussol, Bertrand
Faguer, Stanislas
Gobert, Pierre
Gondran, Guillaume
Huart, Antoine
Hummel, Aurélie
Kalbacher, Emilie
Karras, Adexandre
Lambert, Marc
Le Guern, Véronique
Lebourg, Ludivine
Loubière, Sandrine
Maillard-Lefebvre, Hélène
Maurier, François
Pha, Micheline
Queyrel, Viviane
Remy, Philippe
Sarrot-Reynauld, Françoise
Verhelst, David
Hachulla, Eric
Amoura, Zahir
Daugas, Eric
author_facet Jourde-Chiche, Noemie
Costedoat-Chalumeau, Nathalie
Baumstarck, Karine
Loundou, Anderson
Bouillet, Laurence
Burtey, Stéphane
Caudwell, Valérie
Chiche, Laurent
Couzi, Lionel
Daniel, Laurent
Deligny, Christophe
Dussol, Bertrand
Faguer, Stanislas
Gobert, Pierre
Gondran, Guillaume
Huart, Antoine
Hummel, Aurélie
Kalbacher, Emilie
Karras, Adexandre
Lambert, Marc
Le Guern, Véronique
Lebourg, Ludivine
Loubière, Sandrine
Maillard-Lefebvre, Hélène
Maurier, François
Pha, Micheline
Queyrel, Viviane
Remy, Philippe
Sarrot-Reynauld, Françoise
Verhelst, David
Hachulla, Eric
Amoura, Zahir
Daugas, Eric
author_sort Jourde-Chiche, Noemie
collection PubMed
description OBJECTIVES: Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN. METHODS: WIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2–3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events. RESULTS: Between 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI −1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups. CONCLUSIONS: Non-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares. TRIAL REGISTRATION NUMBER: NCT01284725.
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spelling pubmed-94843652022-09-20 Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial Jourde-Chiche, Noemie Costedoat-Chalumeau, Nathalie Baumstarck, Karine Loundou, Anderson Bouillet, Laurence Burtey, Stéphane Caudwell, Valérie Chiche, Laurent Couzi, Lionel Daniel, Laurent Deligny, Christophe Dussol, Bertrand Faguer, Stanislas Gobert, Pierre Gondran, Guillaume Huart, Antoine Hummel, Aurélie Kalbacher, Emilie Karras, Adexandre Lambert, Marc Le Guern, Véronique Lebourg, Ludivine Loubière, Sandrine Maillard-Lefebvre, Hélène Maurier, François Pha, Micheline Queyrel, Viviane Remy, Philippe Sarrot-Reynauld, Françoise Verhelst, David Hachulla, Eric Amoura, Zahir Daugas, Eric Ann Rheum Dis Systemic Lupus Erythematosus OBJECTIVES: Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN. METHODS: WIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2–3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events. RESULTS: Between 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI −1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups. CONCLUSIONS: Non-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares. TRIAL REGISTRATION NUMBER: NCT01284725. BMJ Publishing Group 2022-10 2022-06-20 /pmc/articles/PMC9484365/ /pubmed/35725295 http://dx.doi.org/10.1136/annrheumdis-2022-222435 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Systemic Lupus Erythematosus
Jourde-Chiche, Noemie
Costedoat-Chalumeau, Nathalie
Baumstarck, Karine
Loundou, Anderson
Bouillet, Laurence
Burtey, Stéphane
Caudwell, Valérie
Chiche, Laurent
Couzi, Lionel
Daniel, Laurent
Deligny, Christophe
Dussol, Bertrand
Faguer, Stanislas
Gobert, Pierre
Gondran, Guillaume
Huart, Antoine
Hummel, Aurélie
Kalbacher, Emilie
Karras, Adexandre
Lambert, Marc
Le Guern, Véronique
Lebourg, Ludivine
Loubière, Sandrine
Maillard-Lefebvre, Hélène
Maurier, François
Pha, Micheline
Queyrel, Viviane
Remy, Philippe
Sarrot-Reynauld, Françoise
Verhelst, David
Hachulla, Eric
Amoura, Zahir
Daugas, Eric
Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
title Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
title_full Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
title_fullStr Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
title_full_unstemmed Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
title_short Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial
title_sort weaning of maintenance immunosuppressive therapy in lupus nephritis (win-lupus): results of a multicentre randomised controlled trial
topic Systemic Lupus Erythematosus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484365/
https://www.ncbi.nlm.nih.gov/pubmed/35725295
http://dx.doi.org/10.1136/annrheumdis-2022-222435
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