Background/Purpose: Management of SLE and lupus nephritis is challenging as it is always a trade off between remission, prevention of relapse and long term adverse effects of drugs. No previous trial has  compared oral mycophenolate mofetil (MMF) with low dose intravenous cyclophosphamide (CYC) as induction agent followed by azathioprine as maintenance agent in the treatment of less severe lupus nephritis (LN).

Methods: This study is a follow-up study of previous open label, ongoing prospective, randomized trial comparing the efficacy and safety of low dose CYC (Euro-lupus regimen) and oral MMF in subjects with class III, IV, V, III+V, or IV+V LN. Subjects with crescentic LN, serum creatinine >3mg/dl, neurological or pulmonary lupus, ongoing infection, pregnancy and prior CYC or MMF use were excluded. The dose of MMF was 2–3 gm/day for 6 months, while CYC was administered as six fortnightly infusions of 500 mg each. All subjects also received three consecutive intravenous methylprednisolone injections initially followed by oral steroids at 1mg/kg up to 2 months and then tapered to a dose of 5-7.5 mg/day. After completion of induction treatment, all subjects were prescribed azathioprine (2 mg/kg) with low dose steroid.

Results: A total of 100 subjects were randomized, of which 69 completed one year of maintenance treatment with azathioprine after receiving either MMF or CYC as induction agent. Out of these 69 subjects, thirty four (n=34) received CYC and thirty five received MMF (n=35) as an induction agent. Baseline characteristics were similar except for a higher 24 hour protein excretion in the CYC group. Sixty one of total subjects, i.e.88.4%, (n=32 in CYC and n =29 in MMF, p=ns) achieved treatment response, of which fifty seven subjects achieved remission. Mean duration to achieve remission in CYC arm was 21.81 weeks and 19.47 weeks in MMF arm. Eight patients had resistant disease (MMF =6, CYC=2), six deaths (MMF=5, CYC=1), four lost to follow up (MMF=1, CYC=3) and one patient deviated from protocol. Four subjects, 3 in MMF and 1 in CYC arm had nephrotic flare during follow up and none had nephritic flare. Gastrointestinal symptoms were more frequent in the MMF group; however there was no difference in other adverse events. Main adverse events during maintenance phase were cytopenia in one patient, herpes zoster in one and avascular necrosis of femoral head in one patient. The treatment cost of MMF was ten times more than the CYC therapy.

Conclusion: One year outcome of maintenance phase with azathioprine were similar in low dose intravenous CYC and oral MMF arm in treatment of less severe lupus nephritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/outcomes-in-lupus-nephritis-patients-previously-randomized-to-receive-either-low-dose-cyclophosphamide-versus-oral-mycophenolate-mofetil-on-azathioprine-maintenance/