Background/Purpose:

To evaluate the efficacy and tolerability of a combination of mycophenolate mofetil (MMF) and tacrolimus (Tac) for refractory lupus nephritis

Methods:

Patients with refractory lupus nephritis were recruited.  Inclusion criteria: (1) Active nephritis documented by renal biopsy within 24 months; (2) Failure to respond to >=2 regimens which consisted of high-dose corticosteroid combined with another non-corticosteroid immunosuppressive agent together with ACE inhibitors.  Each regimen should be used for ³4 months at the maximally tolerated dosages of drugs.  Exclusion criteria: (1) Previous intolerance to either MMF/Tac; and (2) 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 values; (2) Deteriorating Scr by ³20% or loss in creatinine clearance (CrCl) by ³30% not accounted by causes other than active nephritis; (3) Persistently active urinary sediments (RBC, active cellular casts ³5/HPF).  While prednisolone (£10mg/day) and ACE inhibitors were continued, other immunosuppressive agents were replaced by combined MMF (1g/day) and Tac (4mg/day).  Patients were followed 2-monthly for the primary end-point (clinical response) at 12 months and adverse events.

Results:

18 patients (17 women) were recruited. The mean age of these patients was 35.3±9.9 years and the mean SLE duration was 112±46 months. The distribution of the ISN/RPS histological classes of lupus nephritis were: class IV/III (33%), pure V (39%), V+III/IV (28%). Previous treatment regimens were: high-dose prednisolone (100%), CYC (pulse/oral) (39%), AZA (89%), MMF (89%), CSA (28%) and Tac (39%).  The mean Scr, CrCl, uP/Cr, and serum albumin was 83.6±29umol/L, 83.9±30ml/min (56% <90ml/min), 3.00±1.3 and 29.4±5.7g/L, respectively. Twelve (67%) patients had active urinary sediments and 13 (72%) patients had active lupus serology.  After 12 months, 7 (39%) patients had very good response (uP/Cr<0.5; return of lupus serology to baseline; improvement / stabilization of CrCl; and resolution of urinary sediments), 1 (6%) patient had good response (uP/Cr<1.0; improvement in lupus serology and urinary sediments; and stabilization of CrCl) and 3 (17%) patients had partial response (50% improvement in uP/Cr and to <3.0; improvement in serology and urinary sediments; and stabilization of CrCl).  Seven (39%) did not respond to the protocol and required further salvage treatment.  For those patients who responded to treatment, significantly improvement in uP/Cr, serum albumin and anti-dsDNA titer was observed.  CrCl in these patients did not change significantly.  27 adverse events were reported: major infection (7%), minor infection including herpes zoster (41%), diarrhea (7%), dyspepsia / anorexia (7%), transient increase in serum Cr (7%), cramps (7%), alopecia (4%), facial twitching (4%), diabetes mellitus (4%) and others (11%).  None of these had led to protocol withdrawal.

Conclusion:

Combined MMF and Tac is a viable option for refractory lupus nephritis, with 61% patients improves after 12 months without significant adverse effects.

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« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/combination-of-mycophenolate-mofetil-and-tacrolimus-for-refractory-lupus-nephritis-a-12-month-open-labeled-trial/