The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus
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)...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 2015
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| In: |
Annals of the rheumatic diseases
Year: 2015, Volume: 74, Issue: 7, Pages: 1474-1478 |
| ISSN: | 1468-2060 |
| DOI: | 10.1136/annrheumdis-2014-206016 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1136/annrheumdis-2014-206016 Verlag, kostenfrei, Volltext: http://ard.bmj.com/content/74/7/1474 
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| Author Notes: | Tobias Alexander, Ramona Sarfert, Jens Klotsche, Anja A. Kühl, Andrea Rubbert-Roth, Hannes-Martin Lorenz, Jürgen Rech, Bimba F. Hoyer, Qingyu Cheng, Aderajew Waka, Adriano Taddeo, Michael Wiesener, Georg Schett, Gerd-Rüdiger Burmester, Andreas Radbruch, Falk Hiepe, Reinhard E. Voll |
| Summary: | 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/m2) 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 (∼60%) than vaccine-induced protective antibody titres (∼30%). Bortezomib significantly reduced the numbers of peripheral blood and bone marrow PCs (∼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. |
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| Item Description: | Gesehen am 05.04.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1468-2060 |
| DOI: | 10.1136/annrheumdis-2014-206016 |