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SAT0203 Successful treatment of refractory SLE patients with the proteasome inhibitor bortezomib – a case series
  1. R.E. Voll1,2,
  2. T. Alexander3,4,
  3. R. Peukert2,
  4. A. Rubbert5,
  5. J. Rech2,
  6. T. Braun2,
  7. M. Wiesener6,
  8. K.-U. Eckardt6,
  9. B. Hoyer3,4,
  10. A. Taddeo4,
  11. A. Reisch2,
  12. G.-R. Burmester3,4,
  13. A. Radbruch4,
  14. G. Schett2,
  15. F. Hiepe3,4
  1. 1Rheumatology and Clinical Immunlogy, University Medical Center Freiburg, Freiburg
  2. 2Rheumatology and Clinical Immunlogy, University Erlangen-Nürnberg, Erlangen
  3. 3Rheumatology, Charite University Medicine
  4. 4Deutsches Rheumaforschungszentrum, Berlin
  5. 5Hemato-oncology, Section Rheumatology, University Cologne, Cologne
  6. 6Nephrology, University Erlangen-Nürnberg, Erlangen, Germany

Abstract

Background Long-lived plasma cells secreting pathogenic autoantibodies may contribute to refractory disease courses of SLE, because long-lived plasma cells are resistant to conventional therapies (1). We showed that the proteasome inhibitor bortezomib, which is approved for the treatment of relapsed multiple myeloma, eliminates plasma cells including long-lived ones and ameliorates lupus nephritis in mouse models of SLE (2).

Objectives We collected data of all refractory SLE patients treated with bortezomib in our clinics to investigate the efficacy and potential side effects of bortezomib treatment in a case series.

Methods At 3 university centers we treated 13 patients with bortezomib, who had not sufficiently responded to tr did not tolerate conventional drugs. The patients had given informed consent to off-label treatment before they received bortezomib intravenously at a dose of 1.3 mg/m2 body surface at day 1, 4 and 8, some additionally at day 11. Most patients also received 20 mg of dexamethasone together with bortezomib. Treatment cycles were repeated up to four times with an time interval of usually 10 to 14 days in-between cycles. The following clinical and laboratory parameters were monitored: SLEDAI, urine sediment, circulating plasma cells, 24 hour-proteinuria, creatinine clearance, complement C3 and C4, antibodies to double-stranded (ds) DNA and ENA, vaccine antibody titers to hepatits B surface antigen and tetanus toxoid.

Results No serious side effects were observed upon bortezomib treatment. One patient experienced myalgias, fever and headache next day after the first 3 bortezomib applications. Three of seven patients who were treated with 4 bortezomib injections per cycle developed polyneuropathies, which were reversible upon discontinuation of treatment. One patient developed a reversible thrombocytopenia after 4 treatment cycles, no other relevant hematologic toxicities were observed. The disease activity score SLEDAI and anti-dsDNA antibody titers significantly decreased in all patients, in a few patients anti-dsDNA nearly disappeared, whereas ENAs were decreased by up to 50% only. In general, complement levels increased. In all patients with active lupus nephritis, proteinuria declined within 6 weeks of treatment; one patient reached normal protein excretion within 4 months. Protective vaccine antibody titers to hepatitis B surface antigen and tetanus toxoid decreased, but remained within the protective range. Total IgG levels slightly declined in most patients.

Conclusions The proteasome inhibitor bortezomib may provide an effective new therapy for refractory SLE. Pathogenic antibodies, but also protective antibody titers decline upon bortezomib treatment. Clinical trials should be initiated to explore the use of bortezomib as induction therapy in patients with refractory SLE.

  1. Hiepe F. et al. Nat Rev Rheumatol 2011, 7: 170-178.

  2. Neubert K. et al., Nat Med. 2008, 14: 748-755.

Disclosure of Interest None Declared

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