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