The short-term efficacy of bortezomib combined with glucocorticoids for the treatment of refractory lupus nephritis

Lupus. 2017 Aug;26(9):952-958. doi: 10.1177/0961203316686703. Epub 2017 Jan 6.

Abstract

Objective The treatment of refractory lupus nephritis (LN) remains challenging for clinicians because these patients either do not respond to conventional therapy or relapse during the maintenance treatment period. The aim of this study was to investigate the efficacy and safety of bortezomib combined with glucocorticoids in refractory lupus patients. Methodology Five refractory LN patients aged 21 to 43 years (four females and one male) with biopsy-proven diagnosis (four with type IV and one with type V+IV) were recruited. These patients received bortezomib therapy for four cycles (1.3 mg per square meter of body surface area as an intravenous bolus on days 1, 4, 8, and 11 of 21-day cycles) and glucocorticoids (methylprednisolone 0.5 g/d intravenously for three days, followed by prednisone 0.6 mg/kg/d orally for four weeks, with gradual tapering to 10 mg/d). Proteinuria, serum albumin and creatinine, and immunological parameters were assessed, and adverse effects were also evaluated. Results After two to four bortezomib treatment cycles, four patients achieved partial remission with decreases in SLE disease activity index scores from the range of 12-16 to that of 4-8. The patients also exhibited a decline in proteinuria and an elevation of albumin level after treatment. SCr level was decreased in three of five patients with elevated SCr at baseline. The anti-autoantibodies and complements were also improved. Adverse events were of grades 1-2 and included transient thrombocytopenia, gastrointestinal symptoms and acroesthesia. During a 6- to 24-month follow-up period, three patients achieved complete remission, and one had partial remission. However, one patient received renal replacement therapy. Conclusion Bortezomib combined with glucocorticoids reduces proteinuria, improves renal function and decreases anti-autoantibodies, with good tolerance and mild adverse events, thus representing an alternative therapy for refractory LN and warranting further study.

Keywords: Lupus nephritis; adverse effect; bortezomib; efficacy.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Autoantibodies / drug effects
  • Bortezomib / administration & dosage
  • Bortezomib / adverse effects
  • Bortezomib / pharmacology*
  • Drug Therapy, Combination / methods*
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney / drug effects
  • Kidney / physiology
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / pathology
  • Male
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / adverse effects
  • Methylprednisolone / pharmacology*
  • Prednisone / administration & dosage
  • Prednisone / pharmacology*
  • Proteinuria / drug therapy
  • Remission Induction

Substances

  • Antineoplastic Agents
  • Autoantibodies
  • Glucocorticoids
  • Immunosuppressive Agents
  • Bortezomib
  • Prednisone
  • Methylprednisolone