Alexander, Tobias, Sarfert, Ramona, Klotsche, Jens, Kuehl, Anja A., Rubbert-Roth, Andrea, Lorenz, Hannes-Martin, Rech, Juergen, Hoyer, Bimba F., Cheng, Qingyu, Waka, Aderajew, Taddeo, Adriano ORCID: 0000-0003-3281-1548, Wiesener, Michael, Schett, Georg, Burmester, Gerd-Ruediger, Radbruch, Andreas, Hiepe, Falk and Voll, Reinhard E. (2015). The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus. Ann. Rheum. Dis., 74 (7). S. 1474 - 1479. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2060

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Abstract

Objectives To investigate whether bortezomib, a proteasome inhibitor approved for treatment of multiple myeloma, induces clinically relevant plasma cell (PC) depletion in patients with active, refractory systemic lupus erythematosus (SLE). Methods Twelve patients received a median of two (range 1-4) 21-day cycles of intravenous bortezomib (1.3 mg/m(2)) with the coadministration of dexamethasone (20 mg) for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti-double-stranded DNA (anti-dsDNA) and vaccine-induced protective antibodies were monitored. Flow cytometry was performed to analyse peripheral blood B-cells, PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN) activity. Results Upon proteasome inhibition, disease activity significantly declined and remained stable for 6 months on maintenance therapies. Nineteen treatment-emergent adverse events occurred and, although mostly mild to moderate, resulted in treatment discontinuation in seven patients. Serum antibody levels significantly declined, with greater reductions in anti-dsDNA (similar to 60%) than vaccine-induced protective antibody titres (similar to 30%). Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (similar to 50%), but their numbers increased between cycles. Siglec-1 expression on monocytes significantly declined. Conclusions These findings identify proteasome inhibitors as a putative therapeutic option for patients with refractory SLE by targeting PCs and type-I IFN activity, but our results must be confirmed in controlled trials.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Alexander, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sarfert, RamonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klotsche, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuehl, Anja A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubbert-Roth, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorenz, Hannes-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rech, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyer, Bimba F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cheng, QingyuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waka, AderajewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taddeo, AdrianoUNSPECIFIEDorcid.org/0000-0003-3281-1548UNSPECIFIED
Wiesener, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schett, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burmester, Gerd-RuedigerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radbruch, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hiepe, FalkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voll, Reinhard E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-399932
DOI: 10.1136/annrheumdis-2014-206016
Journal or Publication Title: Ann. Rheum. Dis.
Volume: 74
Number: 7
Page Range: S. 1474 - 1479
Date: 2015
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-2060
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RELAPSED MULTIPLE-MYELOMA; DOSE DEXAMETHASONE; DISEASE; THERAPY; CARFILZOMIB; NEPHRITIS; REJECTION; MEMORY; MICEMultiple languages
RheumatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39993

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