TY - JOUR T1 - The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1474 LP - 1478 DO - 10.1136/annrheumdis-2014-206016 VL - 74 IS - 7 AU - Tobias Alexander AU - Ramona Sarfert AU - Jens Klotsche AU - Anja A Kühl AU - Andrea Rubbert-Roth AU - Hannes-Martin Lorenz AU - Jürgen Rech AU - Bimba F Hoyer AU - Qingyu Cheng AU - Aderajew Waka AU - Adriano Taddeo AU - Michael Wiesener AU - Georg Schett AU - Gerd-Rüdiger Burmester AU - Andreas Radbruch AU - Falk Hiepe AU - Reinhard E Voll Y1 - 2015/07/01 UR - http://ard.bmj.com/content/74/7/1474.abstract N2 - 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. ER -