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ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial

INTRODUCTION: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical)...

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Autores principales: Dirikgil, Ebru, van Leeuwen, Jolijn R, van Dam, Laura S, Bredewold, Obbo W, Ray, Argho, Jonker, Jacqueline T, Soonawala, Darius, Remmelts, Hilde H F, van Dam, Bastiaan, Bos, Willem Jan, van Kooten, Cees, Rotmans, Joris, Rabelink, Ton, Teng, Y K Onno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494556/
https://www.ncbi.nlm.nih.gov/pubmed/36130755
http://dx.doi.org/10.1136/bmjopen-2022-061339
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author Dirikgil, Ebru
van Leeuwen, Jolijn R
van Dam, Laura S
Bredewold, Obbo W
Ray, Argho
Jonker, Jacqueline T
Soonawala, Darius
Remmelts, Hilde H F
van Dam, Bastiaan
Bos, Willem Jan
van Kooten, Cees
Rotmans, Joris
Rabelink, Ton
Teng, Y K Onno
author_facet Dirikgil, Ebru
van Leeuwen, Jolijn R
van Dam, Laura S
Bredewold, Obbo W
Ray, Argho
Jonker, Jacqueline T
Soonawala, Darius
Remmelts, Hilde H F
van Dam, Bastiaan
Bos, Willem Jan
van Kooten, Cees
Rotmans, Joris
Rabelink, Ton
Teng, Y K Onno
author_sort Dirikgil, Ebru
collection PubMed
description INTRODUCTION: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical) remission, frequency and severity of relapses is equivalent for both therapies, but there is accumulating data that the long-term safety profile of RTX might outperform CYC. Combination of RTX with low-dose CYC (LD-CYC) has been investigated in only a few uncontrolled cohort studies, in which clinical remission and a favourable immunological state with low relapse rates was quickly achieved. In this randomised controlled trial, we aim to investigate whether the combination treatment (RTX+LD CYC) is superior in comparison to standard care with RTX only. METHODS AND ANALYSIS: This study is an open-label, multicentre, 1:1 randomised, prospective study for patients with AAV with generalised disease, defined as involvement of major organs, that is, kidneys, lungs, heart and nervous system. In total, 100 patients will be randomised 1:1 to receive either remission induction therapy with standard of care (RTX) or combination treatment (RTX+LD CYC) in addition to steroids and both arms are followed by maintenance with RTX retreatments (tailored to B-cell and ANCA status). Our primary outcome is the number of retreatments needed to maintain clinical remission over 2 years. Secondary outcomes are relevant clinical endpoints, safety, quality of life and immunological responses. ETHICS AND DISSEMINATION: This study has received approval of the Medical Ethics Committee of the Leiden University Medical Center (P18.216, NL67515.058.18, date: 7 March 2019). The results of this trial (positive and negative) will be submitted for publication in relevant peer-reviewed publications and the key findings presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03942887.
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spelling pubmed-94945562022-09-23 ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial Dirikgil, Ebru van Leeuwen, Jolijn R van Dam, Laura S Bredewold, Obbo W Ray, Argho Jonker, Jacqueline T Soonawala, Darius Remmelts, Hilde H F van Dam, Bastiaan Bos, Willem Jan van Kooten, Cees Rotmans, Joris Rabelink, Ton Teng, Y K Onno BMJ Open Rheumatology INTRODUCTION: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical) remission, frequency and severity of relapses is equivalent for both therapies, but there is accumulating data that the long-term safety profile of RTX might outperform CYC. Combination of RTX with low-dose CYC (LD-CYC) has been investigated in only a few uncontrolled cohort studies, in which clinical remission and a favourable immunological state with low relapse rates was quickly achieved. In this randomised controlled trial, we aim to investigate whether the combination treatment (RTX+LD CYC) is superior in comparison to standard care with RTX only. METHODS AND ANALYSIS: This study is an open-label, multicentre, 1:1 randomised, prospective study for patients with AAV with generalised disease, defined as involvement of major organs, that is, kidneys, lungs, heart and nervous system. In total, 100 patients will be randomised 1:1 to receive either remission induction therapy with standard of care (RTX) or combination treatment (RTX+LD CYC) in addition to steroids and both arms are followed by maintenance with RTX retreatments (tailored to B-cell and ANCA status). Our primary outcome is the number of retreatments needed to maintain clinical remission over 2 years. Secondary outcomes are relevant clinical endpoints, safety, quality of life and immunological responses. ETHICS AND DISSEMINATION: This study has received approval of the Medical Ethics Committee of the Leiden University Medical Center (P18.216, NL67515.058.18, date: 7 March 2019). The results of this trial (positive and negative) will be submitted for publication in relevant peer-reviewed publications and the key findings presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03942887. BMJ Publishing Group 2022-09-21 /pmc/articles/PMC9494556/ /pubmed/36130755 http://dx.doi.org/10.1136/bmjopen-2022-061339 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 Rheumatology
Dirikgil, Ebru
van Leeuwen, Jolijn R
van Dam, Laura S
Bredewold, Obbo W
Ray, Argho
Jonker, Jacqueline T
Soonawala, Darius
Remmelts, Hilde H F
van Dam, Bastiaan
Bos, Willem Jan
van Kooten, Cees
Rotmans, Joris
Rabelink, Ton
Teng, Y K Onno
ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial
title ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial
title_full ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial
title_fullStr ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial
title_full_unstemmed ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial
title_short ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial
title_sort exploring durable remission with rituximab in anca-associated vasculitis (endurrance trial): protocol for a randomised controlled trial
topic Rheumatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494556/
https://www.ncbi.nlm.nih.gov/pubmed/36130755
http://dx.doi.org/10.1136/bmjopen-2022-061339
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