Objectives To evaluate the efficacy and tolerability of combined low-dose mycophenolate mofetil (MMF) and tacrolimus (Tac) for refractory lupus nephritis
Methods Patients with refractory lupus nephritis were recruited. Inclusion criteria: (1) Active nephritis by renal biopsy within 24 months; (2) Failure to respond to >=2 regimens which consisted of high-dose corticosteroid + another non-corticosteroid immunosuppressive agent (eg. cyclophosphamide[CYC], azathioprine[AZA], cyclosporin A[CSA], MMF or Tac) together with ACE inhibitors ± angiotensin receptor blockers(ARB). Each regimen should be used for >=4 months at the maximally tolerated dosages; (3) Serum creatinine(Scr) >200umol/L. Treatment failure to previous regimens, defined as any one of the following: (1) Failure of proteinuria to improve to <3g/day or urine protein-to-creatinine (uP/Cr) ratio to <3.0; or <50% of pre-treatment / baseline values; (2) Deteriorating Scr by >=20% or loss in creatinine clearance (CrCl) by >30% compared to baseline not accounted by causes other than active nephritis; (3) Persistently active urinary sediments (RBC, active cellular casts >5/HPF). While prednisolone (<10mg/day), ACE inhibitors/ARB and hydroxychloroquine were continued, other immunosuppressive agents were discontinued and replaced by the current regimen, which consisted of MMF (1g/day) and Tac (4mg/day) in two divided doses. Patients were followed prospectively at least 2-monthly for the primary end-point (clinical response) at 12 months and adverse events.
Results 21 patients were recruited (20 women; age 35.8±9.2 years; SLE duration 111±51 months). The histological classes of lupus nephritis were: IV/III(33%), V+III/IV(33%) and pure V(33%). Previous ineffective immunosuppressive regimens included were: high-dose prednisolone (>=0.75mg/kg/day for ³6 weeks) (100%), CYC (0.75-1g/m2 pulse or 2mg/kg/day oral) (38%), AZA (2mg/kg/day) (90%), MMF (2-3g/day) (90%), CSA (5mg/kg/day) (33%) and TAC (0.1mg/kg/day) (38%). The creatinine clearance (CrCl), urine protein-to-creatinine ratio (uP/Cr) and serum albumin was 82.4±33ml/min (<90ml/min in 57%), 3.27±1.5 and 30.1±5.9g/L, respectively. Thirteen(62%) patients had active urinary sediments and 17(81%) patients had active lupus serology. At 12 months, 8(38%) patients had very good response, 1(5%) patient had good response and 5(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(6%), minor infection including herpes zoster(36%), 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 MMF and Tac is a viable option for refractory lupus nephritis, with 61% patients improves after 12 months without significant adverse effects.
Disclosure of Interest None Declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.