Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis

Abstract

No previous study has compared mycophenolate mofetil (MMF) with low-dose cyclophosphamide (CYC) in the treatment of lupus nephritis (LN). To do so, we recruited patients with LN (class III, IV, or V) and randomized them to receive either low-dose CYC or oral MMF. Those with crescentic LN, a serum creatinine over 265 μmol/l, and neurological or pulmonary lupus were excluded. MMF was prescribed at daily doses of 1.5-3 g for 24 weeks, while CYC was administered as six fortnightly infusions of 500 mg each. All patients received three methylprednisolone injections, followed by oral corticosteroids. Maintenance therapy with azathioprine and low-dose corticosteroid was started at end of induction therapy. The primary end point was treatment response at 24 weeks, while secondary end points were complete remission, Systemic Lupus Erythematosus Disease Activity Index and adverse events. Of the 173 patients recruited, 100 were equally randomized to receive either CYC or MMF. Baseline characteristics were similar, except for higher 24 h proteinuria in the CYC group. At 24 weeks, 37 patients in each group achieved the primary end point. The complete remission rate was 50% in CYC and 54% in MMF group. Gastrointestinal symptoms were significantly more frequent in patients receiving MMF (52 vs. 4%). However, other adverse events were similar. Thus, low-dose intravenous CYC is comparable in safety and efficacy to oral MMF in the induction treatment of less severe LN.

Kidneys and women's health: key challenges and considerations

“…Lupus affects eight times as many women as men 37 and the cheapest effective treatment for lupus nephritis, cyclophosphamide, can impair fertility if the dose is not minimized and the ovaries are not protected 38 . This risk deters women from accepting treatment.…”

Comparison of renal response to four different induction therapies in Japanese patients with lupus nephritis class III or IV: A single-centre retrospective study

“…Since low-dose ELNT-IVCY has been mainly evaluated in European patients [6], a higher dose of cyclophosphamide might be needed for Asians. Rathi M et al recently reported, in a head-to-head trial comparing ELNT-IVCY and MMF in an Indian population, that the CR rate at 6 months was not significantly different between the two groups [7]. Further investigation is needed regarding appropriate dosage of IVCY in Asians, especially the Japanese population.…”

“…The low dose IVCY regimen was recommended for whites with European background based on the results of Euro Lupus Nephritis Trial (ELNT). In contrast, there have been few investigations of the efficacy and safety of the ELNT protocols focused on other ethnic groups or races, especially Asians [7]. Recently, tacrolimus (TAC) for induction therapy had a good outcome in Chinese patients with lupus nephritis in a short-term study [8].…”

Current and Emerging Therapies for Lupus Nephritis

“…However, the short-term efficacy of low-dose cyclophosphamide was recently verified in a racially diverse North American population 15 and a southeast Asian cohort. 16 Like the ELNT investigators, others sought to eliminate the cyclophosphamidespecific risks of premature ovarian failure and future malignancies by substituting mycophenolate mofetil (MMF) for cyclophosphamide in LN induction. 17 Several trials suggested equivalence or superiority of MMF in achieving short-term renal responses, 18,19 however in the largest trial, the Aspreva Lupus Management Study (ALMS), MMF and cyclophosphamide were found to be equivalent at the 24-week end point.…”