Multidrug, multitarget regimen may result in higher remission rates for lupus nephritis

A multidrug, multitarget regimen was superior to intravenous cyclophosphamide as induction therapy for lupus nephritis, according to a randomized, controlled trial.

Researchers sought to assess the efficacy and safety of a regimen of tacrolimus, mycophenolate mofetil, and steroid compared with intravenous cyclophosphamide and steroid. They enrolled 368 patients between the ages of 18 and 65 years with lupus nephritis from 26 renal centers in China. All patients received intravenous methylprednisolone pulse therapy for 3 days, followed by a dose of oral prednisone (0.6 mg/kg per day) each morning for 4 weeks. Prednisone was tapered by 5 mg/d every day for 2 weeks and then by 2.5 mg/d every 2 weeks. The maintenance dose of prednisone was 10 mg/d.

After the initial treatment, patients were randomly assigned to 1 of 2 treatment groups. The multitarget group received mycophenolate mofetil (0.5 g) and tacrolimus (2 mg) 2 times per day. The intravenous cyclophosphamide group received cyclophosphamide at a dose of 0.75 g/m² body surface area and then an adjusted dose of 0.5 to 1.0 g/m² body surface area every 4 weeks for 6 doses. The patients were evaluated at 2 and 4 weeks and then every 4 weeks until 24 weeks for changes in levels of proteinuria and serum albumin and drug-related adverse effects.

Results were published online Nov. 11 by Annals of Internal Medicine.

After 24 weeks of therapy, more patients in the multitarget group (45.9%) than in the intravenous cyclophosphamide group (25.6%) showed complete remission (difference, 20.3 percentage points [95% CI, 10.0 to 30.6 percentage points]; P<0.001). The overall response was higher in the multitarget group than in the intravenous cyclophosphamide group (83.5% vs. 63.0%; difference, 20.4 percentage points [95% CI, 10.3 to 30.6 percentage points]; P<0.001). Also, the median time to response was shorter in the multitarget group (difference, −4.1 weeks [95% CI, −7.9 to −2.1 weeks]). Adverse events did not differ between the multitarget and intravenous cyclophosphamide groups (50.3% vs. 52.5%).

The authors suggested that the multitarget regimen should be considered as an alternative to conventional therapies for lupus nephritis, although they cautioned that 6 months of follow-up may be too short to differentiate between study treatments because the disease may continue to improve. Also, patients with a renal chronicity index greater than 3 were excluded, which may have excluded some patients with chronic disease that later became more severe.

For more on diagnosing and managing patients with systemic lupus erythematosus, read ACP Internist's November/December cover story.