THU0274 Combination of Mycophenolate Mofetil and Tacrolimus for Refractory Lupus Nephritis: A 12-Month Open-Labeled Trial
Authors: C. C. Mok, P. T. Chan, L. Y. Ho, C. H. To
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the efficacy and tolerability of combined low-dose mycophenolate mofetil (MMF) and tacrolimus (Tac) for refractory lupus nephritis <h3>Methods</h3> Patients with refractory lupus nephritis were recruited. Inclusion criteria: (1) Active nephritis by renal biopsy within 24 months; (2) Failure to respond to &gt;=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 &gt;=4 months at the maximally tolerated dosages; (3) Serum creatinine(Scr) &gt;200umol/L. Treatment failure to previous regimens, defined as any one of the following: (1) Failure of proteinuria to improve to &lt;3g/day or urine protein-to-creatinine (uP/Cr) ratio to &lt;3.0; or &lt;50% of pre-treatment / baseline values; (2) Deteriorating Scr by &gt;=20% or loss in creatinine clearance (CrCl) by &gt;30% compared to baseline not accounted by causes other than active nephritis; (3) Persistently active urinary sediments (RBC, active cellular casts &gt;5/HPF). While prednisolone (&lt;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. <h3>Results</h3> 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 (&gt;=0.75mg/kg/day for ³6 weeks) (100%), CYC (0.75-1g/m<sup>2</sup> 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 (&lt;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. <h3>Conclusions</h3> Combined MMF and Tac is a viable option for refractory lupus nephritis, with 61% patients improves after 12 months without significant adverse effects. <h3>Disclosure of Interest</h3> None Declared