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Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study

INTRODUCTION: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN). METHODS: Patients with histo...

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Autores principales: Lorenz, Hanns-Martin, Schmitt, Wilhelm H, Tesar, Vladimir, Müller-Ladner, Ulf, Tarner, Ingo, Hauser, Ingeborg A, Hiepe, Falk, Alexander, Tobias, Woehling, Heike, Nemoto, Kyuichi, Heinzel, Peter A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132014/
https://www.ncbi.nlm.nih.gov/pubmed/21356124
http://dx.doi.org/10.1186/ar3268
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author Lorenz, Hanns-Martin
Schmitt, Wilhelm H
Tesar, Vladimir
Müller-Ladner, Ulf
Tarner, Ingo
Hauser, Ingeborg A
Hiepe, Falk
Alexander, Tobias
Woehling, Heike
Nemoto, Kyuichi
Heinzel, Peter A
author_facet Lorenz, Hanns-Martin
Schmitt, Wilhelm H
Tesar, Vladimir
Müller-Ladner, Ulf
Tarner, Ingo
Hauser, Ingeborg A
Hiepe, Falk
Alexander, Tobias
Woehling, Heike
Nemoto, Kyuichi
Heinzel, Peter A
author_sort Lorenz, Hanns-Martin
collection PubMed
description INTRODUCTION: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN). METHODS: Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week. These cycles were repeated to a maximum of nine times. Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4. Response was measured according to a predefined decision pattern. The dose of DSG was adjusted depending on the efficacy and side effects. RESULTS: A total of 21 patients were included in this phase-I/II study. After the first DSG injection, one patient was excluded from the study due to renal failure. Five patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia. Eleven out of 20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and 1 patient was not assessable. Twelve patients completed all nine cycles; in those patients, proteinuria decreased from 5.88 g/day to 3.37 g/day (P = 0.028), Selena-SLEDAI (Safety of Estrogens in Lupus Erythematosus - National Assessment - systemic lupus erythematosus disease activity index) decreased from 17.6 to 11.7. In 13 out of 20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1 g/day. CONCLUSIONS: Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN. The improvement in proteinuria encourages larger controlled trials. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00709722
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spelling pubmed-31320142011-07-09 Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study Lorenz, Hanns-Martin Schmitt, Wilhelm H Tesar, Vladimir Müller-Ladner, Ulf Tarner, Ingo Hauser, Ingeborg A Hiepe, Falk Alexander, Tobias Woehling, Heike Nemoto, Kyuichi Heinzel, Peter A Arthritis Res Ther Research Article INTRODUCTION: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN). METHODS: Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week. These cycles were repeated to a maximum of nine times. Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4. Response was measured according to a predefined decision pattern. The dose of DSG was adjusted depending on the efficacy and side effects. RESULTS: A total of 21 patients were included in this phase-I/II study. After the first DSG injection, one patient was excluded from the study due to renal failure. Five patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia. Eleven out of 20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and 1 patient was not assessable. Twelve patients completed all nine cycles; in those patients, proteinuria decreased from 5.88 g/day to 3.37 g/day (P = 0.028), Selena-SLEDAI (Safety of Estrogens in Lupus Erythematosus - National Assessment - systemic lupus erythematosus disease activity index) decreased from 17.6 to 11.7. In 13 out of 20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1 g/day. CONCLUSIONS: Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN. The improvement in proteinuria encourages larger controlled trials. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00709722 BioMed Central 2011 2011-03-01 /pmc/articles/PMC3132014/ /pubmed/21356124 http://dx.doi.org/10.1186/ar3268 Text en Copyright ©2011 Lorenz et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lorenz, Hanns-Martin
Schmitt, Wilhelm H
Tesar, Vladimir
Müller-Ladner, Ulf
Tarner, Ingo
Hauser, Ingeborg A
Hiepe, Falk
Alexander, Tobias
Woehling, Heike
Nemoto, Kyuichi
Heinzel, Peter A
Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
title Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
title_full Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
title_fullStr Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
title_full_unstemmed Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
title_short Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
title_sort treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132014/
https://www.ncbi.nlm.nih.gov/pubmed/21356124
http://dx.doi.org/10.1186/ar3268
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