Rituximab in the Treatment of Resistant Lupus Nephritis: Therapy Failure in Rapidly Progressive Crescentic Lupus Nephritis

Lupus. 2013 May;22(6):574-82. doi: 10.1177/0961203313483376. Epub 2013 Apr 30.

Abstract

Objective: The objective of this paper is to report the clinical outcome of B cell depletion therapy in 18 patients with refractory lupus nephritis (LN).

Methods: Eighteen patients received rituximab on an open-label basis with prospective evaluations. All patients had renal disease refractory to conventional immunosuppressive therapy, including intravenous cyclophosphamide (CyC). All patients fulfilled the revised ACR classification criteria for SLE. Rituximab was given as 2 × 1 g infusions with 500 mg iv CyC and 500 mg iv methylprednisolone, two weeks apart. Complete remission (CR) of nephritis at six months was defined as normal serum creatinine and serum albumin levels, inactive urine sediment, and proteinuria < 0.5 g/day; partial remission (PR) was defined as a ≥50% improvement in all renal parameters that were abnormal at baseline. Clinical response was assessed by the British Isles Lupus Assessment Group (BILAG) score pre- and post-rituximab treatment, and efficacy was recorded by extent and duration of B lymphocyte depletion (normal range 0.100-0.500 × 10(9)/l). Follow-up data were collected at six months, one year post-treatment and at the most recent clinic visit.

Results: At six months, 11/18 patients reached renal CR and two of 18 PR. The mean global BILAG scores for responders decreased from 15 (SD 10) to 5 (SD 3), and a total of ten A scores disappeared. Five patients failed to show complete or partial renal response despite peripheral B lymphocyte count depletion, and progressed to end-stage renal failure (ESRF) and dialysis. Four of these patients had severe proliferative, crescentic nephritis, of whom three had Class IV-G, one Class III and one late membranous glomerulonephritis. One patient died six years after rituximab therapy from overwhelming sepsis while on long-term haemodialysis.

Conclusion: Rituximab therapy achieved a response in 13/18 patients with refractory LN. However, in patients with rapidly progressive crescentic LN, when there is already evidence of significant renal impairment, rituximab therapy may not prevent progression to ESRF and dialysis. Our data also suggest that severe Class IV-G LN may be associated with a poor response to therapy.

Keywords: B cell depletion; Systemic lupus erythematosus; lupus nephritis.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunosuppressive Agents / therapeutic use
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / physiopathology
  • Male
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Prospective Studies
  • Remission Induction / methods
  • Rituximab
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Immunologic Factors
  • Immunosuppressive Agents
  • Rituximab
  • Cyclophosphamide
  • Methylprednisolone