Mycophenolate mofetil, cyclophosphamide similarly effective in improving renal function markers in LN
The use of the lymphocyte-selective antiproliferative agent mycophenolate mofetil (MMF) in lower doses is as effective as the chemotherapy drug cyclophosphamide in improving kidney function and reducing proteinuria during induction therapy for proliferative lupus nephritis (LN), a Nepalese trial shows.
In this prospective analysis, 42 individuals (mean age 25.93 years) with class III–V LN were randomized 1:1 to receive oral MMF at a maximum daily dose of 1.5 g (750 mg twice/day for weight >50 kg; 500 mg twice/day then increased to 750 mg twice/day after 30 days for weight <50 kg) or a monthly pulse of intravenous cyclophosphamide for a total of six infusions. Baseline mean serum creatinine was 1.58 mg/dL, estimated glomerular filtration rate (eGFR) was 62.38 mL/min/1.73m2, and 24-hour urinary protein was 4.35 g/1.73 m2 body surface area. [BMC Nephrol 2018;19:175]
Despite the numerically higher partial remission rates in the MMF vs the cyclophosphamide arm (28.6 percent vs 19.0 percent) and higher composite renal remission rates with MMF vs cyclophosphamide in spite of the former’s lower dose (85.71 percent vs 76.19 percent), both study drugs similarly reduced serum creatinine (from 1.24 to 0.91 mg/dL and 1.73 to 0.96 mg/dL, respectively) and 24-hour urinary protein (from 4.5 to 0.62 g/1.73 m2 and 4.47 to 0.94 g/1.73 m2), and improved eGFR at 6 months (from 64.42 to 89.09 mL/min/1.73m2 and 60.33 to 88.52 mL/min/1.73m2).
Reductions in SLEDAI* scores signified improvement in disease activity with both MMC and cyclophosphamide, decreasing to 2.34 and 3.23, respectively, at 6 months.
The most common adverse events (AEs) reported were alopecia and nausea/vomiting, which were only observed among cyclophosphamide recipients. No serious AEs requiring drug discontinuation were reported, and overall AE rates were lower with MMF vs cyclophosphamide (n=15 vs 56) with a comparable number of infection-related AEs (n=7 vs 10).
Nonetheless, the numerically higher infection rate in the cyclophosphamide arm warrants attention considering the high prevalence of infections in the region, the researchers pointed out.
Evidence has shown that cyclophosphamide use is associated with dose-dependent short- and long-term toxicities despite its proven efficacy in inducing remission in LN, hence the importance of finding an alternative, noted the researchers. [Lancet 1992;340:741-745; Nephrol Dial Transplant 1997;12:2057-2059; N Engl J Med 1986;314:614-619]
The ALMS** trial demonstrated a better response with MMF vs cyclophosphamide as measured by serum creatinine (70.3 percent vs 67.6 percent) and urinary sediment levels (31.4 percent vs 23.8 percent). [J Am Soc Nephrol 2009;20:1103-1112] The current study reflects better composite outcomes than ALMS despite the small population and the exclusion of urinary sediment measurement in the current trial, the researchers pointed out.
Larger multicentre trials with longer follow-ups are thus warranted to further evaluate the durability of response over the long term and extrapolate the results to LN populations in other parts of the world, said the researchers.