Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial
Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses....
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
van Schaik, Mieke [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Anmerkung: |
© The Author(s) 2022 |
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| Übergeordnetes Werk: |
Enthalten in: Trials - London : BioMed Central, 2000, 23(2022), 1 vom: 12. Nov. |
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| Übergeordnetes Werk: |
volume:23 ; year:2022 ; number:1 ; day:12 ; month:11 |
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| DOI / URN: |
10.1186/s13063-022-06874-w |
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| Katalog-ID: |
SPR051124246 |
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| 245 | 1 | 0 | |a Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial |
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| 520 | |a Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. | ||
| 650 | 4 | |a Systemic autoimmune disease |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Systemic lupus erythematosus |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Lupus nephritis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Belimumab |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Rituximab |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Clinical trial |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Arends, Eline J. |4 aut | |
| 700 | 1 | |a Soonawala, Darius |4 aut | |
| 700 | 1 | |a van Ommen, Ellen |4 aut | |
| 700 | 1 | |a de Leeuw, Karina |4 aut | |
| 700 | 1 | |a Limper, Maarten |4 aut | |
| 700 | 1 | |a van Paassen, Pieter |4 aut | |
| 700 | 1 | |a Huizinga, Tom W. J. |4 aut | |
| 700 | 1 | |a Toes, René E. M. |4 aut | |
| 700 | 1 | |a van Kooten, Cees |4 aut | |
| 700 | 1 | |a Rotmans, Joris I. |4 aut | |
| 700 | 1 | |a Rabelink, Ton J. |4 aut | |
| 700 | 1 | |a Teng, Y. K. Onno |4 aut | |
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10.1186/s13063-022-06874-w doi (DE-627)SPR051124246 (SPR)s13063-022-06874-w-e DE-627 ger DE-627 rakwb eng van Schaik, Mieke verfasserin (orcid)0000-0003-3823-4702 aut Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. Systemic autoimmune disease (dpeaa)DE-He213 Systemic lupus erythematosus (dpeaa)DE-He213 Lupus nephritis (dpeaa)DE-He213 Belimumab (dpeaa)DE-He213 Rituximab (dpeaa)DE-He213 Clinical trial (dpeaa)DE-He213 Arends, Eline J. aut Soonawala, Darius aut van Ommen, Ellen aut de Leeuw, Karina aut Limper, Maarten aut van Paassen, Pieter aut Huizinga, Tom W. J. aut Toes, René E. M. aut van Kooten, Cees aut Rotmans, Joris I. aut Rabelink, Ton J. aut Teng, Y. K. Onno aut Enthalten in Trials London : BioMed Central, 2000 23(2022), 1 vom: 12. Nov. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:23 year:2022 number:1 day:12 month:11 https://dx.doi.org/10.1186/s13063-022-06874-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 12 11 |
| spelling |
10.1186/s13063-022-06874-w doi (DE-627)SPR051124246 (SPR)s13063-022-06874-w-e DE-627 ger DE-627 rakwb eng van Schaik, Mieke verfasserin (orcid)0000-0003-3823-4702 aut Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. Systemic autoimmune disease (dpeaa)DE-He213 Systemic lupus erythematosus (dpeaa)DE-He213 Lupus nephritis (dpeaa)DE-He213 Belimumab (dpeaa)DE-He213 Rituximab (dpeaa)DE-He213 Clinical trial (dpeaa)DE-He213 Arends, Eline J. aut Soonawala, Darius aut van Ommen, Ellen aut de Leeuw, Karina aut Limper, Maarten aut van Paassen, Pieter aut Huizinga, Tom W. J. aut Toes, René E. M. aut van Kooten, Cees aut Rotmans, Joris I. aut Rabelink, Ton J. aut Teng, Y. K. Onno aut Enthalten in Trials London : BioMed Central, 2000 23(2022), 1 vom: 12. Nov. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:23 year:2022 number:1 day:12 month:11 https://dx.doi.org/10.1186/s13063-022-06874-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 12 11 |
| allfields_unstemmed |
10.1186/s13063-022-06874-w doi (DE-627)SPR051124246 (SPR)s13063-022-06874-w-e DE-627 ger DE-627 rakwb eng van Schaik, Mieke verfasserin (orcid)0000-0003-3823-4702 aut Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. Systemic autoimmune disease (dpeaa)DE-He213 Systemic lupus erythematosus (dpeaa)DE-He213 Lupus nephritis (dpeaa)DE-He213 Belimumab (dpeaa)DE-He213 Rituximab (dpeaa)DE-He213 Clinical trial (dpeaa)DE-He213 Arends, Eline J. aut Soonawala, Darius aut van Ommen, Ellen aut de Leeuw, Karina aut Limper, Maarten aut van Paassen, Pieter aut Huizinga, Tom W. J. aut Toes, René E. M. aut van Kooten, Cees aut Rotmans, Joris I. aut Rabelink, Ton J. aut Teng, Y. K. Onno aut Enthalten in Trials London : BioMed Central, 2000 23(2022), 1 vom: 12. Nov. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:23 year:2022 number:1 day:12 month:11 https://dx.doi.org/10.1186/s13063-022-06874-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 12 11 |
| allfieldsGer |
10.1186/s13063-022-06874-w doi (DE-627)SPR051124246 (SPR)s13063-022-06874-w-e DE-627 ger DE-627 rakwb eng van Schaik, Mieke verfasserin (orcid)0000-0003-3823-4702 aut Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. Systemic autoimmune disease (dpeaa)DE-He213 Systemic lupus erythematosus (dpeaa)DE-He213 Lupus nephritis (dpeaa)DE-He213 Belimumab (dpeaa)DE-He213 Rituximab (dpeaa)DE-He213 Clinical trial (dpeaa)DE-He213 Arends, Eline J. aut Soonawala, Darius aut van Ommen, Ellen aut de Leeuw, Karina aut Limper, Maarten aut van Paassen, Pieter aut Huizinga, Tom W. J. aut Toes, René E. M. aut van Kooten, Cees aut Rotmans, Joris I. aut Rabelink, Ton J. aut Teng, Y. K. Onno aut Enthalten in Trials London : BioMed Central, 2000 23(2022), 1 vom: 12. Nov. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:23 year:2022 number:1 day:12 month:11 https://dx.doi.org/10.1186/s13063-022-06874-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 12 11 |
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10.1186/s13063-022-06874-w doi (DE-627)SPR051124246 (SPR)s13063-022-06874-w-e DE-627 ger DE-627 rakwb eng van Schaik, Mieke verfasserin (orcid)0000-0003-3823-4702 aut Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. Systemic autoimmune disease (dpeaa)DE-He213 Systemic lupus erythematosus (dpeaa)DE-He213 Lupus nephritis (dpeaa)DE-He213 Belimumab (dpeaa)DE-He213 Rituximab (dpeaa)DE-He213 Clinical trial (dpeaa)DE-He213 Arends, Eline J. aut Soonawala, Darius aut van Ommen, Ellen aut de Leeuw, Karina aut Limper, Maarten aut van Paassen, Pieter aut Huizinga, Tom W. J. aut Toes, René E. M. aut van Kooten, Cees aut Rotmans, Joris I. aut Rabelink, Ton J. aut Teng, Y. K. Onno aut Enthalten in Trials London : BioMed Central, 2000 23(2022), 1 vom: 12. Nov. (DE-627)326173552 (DE-600)2040523-6 1745-6215 nnns volume:23 year:2022 number:1 day:12 month:11 https://dx.doi.org/10.1186/s13063-022-06874-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 1 12 11 |
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efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label synbiose 2 trial |
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Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial |
| abstract |
Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. © The Author(s) 2022 |
| abstractGer |
Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. © The Author(s) 2022 |
| abstract_unstemmed |
Background Belimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate. Methods Synbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections. Discussion The Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE. Trial registration ClinicalTrials.gov NCT03747159. Registered on 20 November 2018. © The Author(s) 2022 |
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Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial |
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Arends, Eline J. Soonawala, Darius van Ommen, Ellen de Leeuw, Karina Limper, Maarten van Paassen, Pieter Huizinga, Tom W. J. Toes, René E. M. van Kooten, Cees Rotmans, Joris I. Rabelink, Ton J. Teng, Y. K. Onno |
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