Combined Low-Dose Mycophenolate Mofetil and Tacrolimus for Lupus Nephritis With Suboptimal Response to Standard Therapy: A 12-month Prospective Study

Lupus. 2013 Oct;22(11):1135-41. doi: 10.1177/0961203313502864. Epub 2013 Aug 30.

Abstract

Objective: The objective of this paper is to evaluate the efficacy of combined mycophenolate mofetil (MMF) and tacrolimus (TAC) for lupus nephritis with suboptimal response to standard therapy.

Methods: Inclusion criteria for patients: (1) biopsy-confirmed active lupus nephritis; and (2) inadequate response to ≥ 2 immunosuppressive regimens. While prednisolone (≤ 10 mg/day) and angiotensin-converting enzyme inhibitors were continued, immunosuppressive agents were replaced by combined MMF (1 g/day) and TAC (4 mg/day). Patients were followed every 2 months for the clinical response and adverse events at 12 months.

Results: Twenty-one patients were recruited (20 women; age 35.8 ± 9.2 years; systemic lupus erythematosus (SLE) duration 111 ± 51 months). The histological classes of lupus nephritis were: IV/III (33%), V+III/IV (33%) and pure V (33%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4 ± 33 ml/min (<90 ml/min in 57%), 3.27 ± 1.5 and 30.1 ± 5.9 g/l, respectively. Thirteen (62%) patients had active urinary sediments and 17 (81%) patients had active lupus serology. At 12 months, eight (38%) patients had very good response, one (5%) patient had good response and five (24%) patients had partial response. Significant improvement in uP/Cr, albumin, complement C3 and anti-dsDNA titer, and stabilization of CrCl was observed in the responders. Thirty-three adverse events were reported in 18 patients: major infection requiring hospitalization (6%), infection not requiring hospitalization (27%), herpes infection (9%), diarrhea (12%), cramps (9%), dyspepsia (6%), transient increase in serum Cr (6%), alopecia (4%), facial twitching (3%), tremor (3%) and diabetes mellitus (3%). None of these had led to protocol withdrawal.

Conclusions: Combined low-dose MMF and TAC is an option for lupus nephritis that fails to respond adequately to standard regimens, with two-thirds of patients improving after 12 months. Longer-term observation is needed to confirm its efficacy and safety.

Keywords: Glomerulonephritis; nephropathy; recalcitrant; resistant; treatment.

MeSH terms

  • Adult
  • Creatinine / urine
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / immunology
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Prospective Studies
  • Serum Albumin / analysis
  • T-Lymphocytes / immunology
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects

Substances

  • Immunosuppressive Agents
  • Serum Albumin
  • Creatinine
  • Mycophenolic Acid
  • Tacrolimus