The authors of this paper report on the results of a phase 3, double blind, placebo controlled, randomised trial investigating the efficacy and safety of rituximab in lupus nephritis (LN). The authors note that LN may occur in up to 50% of patients with systemic lupus erythematosus (SLE). They investigated whether the addition of rituximab to a background of mycophenolate mofetil (MMF) plus corticosteroids in patients with proliferative LN could improve renal response rates at 52 weeks. Efficacy and safety were also examined as 78 weeks.

A total of 144 patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN were randomised (in a 1:1 ratio) to rituximab (intravenously, 1000 mg; n=72) or placebo (n =72) on days 1, 15, 168, and 182. Patients were recruited from 52 centres across the United States and Latin America. MMF was initiated at 1.5 g/day in 3 divided doses and increased to 3 g/day by week 4 as tolerated. Treatment with MMF at 3 g/day was continued through at least week 52.

The primary efficacy endpoint measure considered in the study was renal response, defined as complete renal response (CRR), partial renal response (PRR), or no response (NR), at week 52. Overall, 88% and 93% of placebo and rituximab patients, respectively, completed 52 weeks of study; 81% and 89% completed 78 weeks. The results found (direct form source):

• CRR and PRR were achieved in 33/72 (45.8%) placebo- and 41/72 (56.9%) rituximab-treated patients (P=0.55), the difference mostly accounted for by partial responses. The primary endpoint (superior response rate with rituximab) was not achieved.

• Rituximab depleted peripheral CD19+ B cells in 71/72 patients (secondary endpoint).

• Eight placebo patients and no rituximab-treated patients required cyclophosphamide rescue therapy through week 52.

• Statistically significant improvements in serum complement C3, C4, and anti-dsDNA antibody levels were observed with rituximab (secondary endpoints). In both treatment groups, a reduction in anti-dsDNA greater than the median reduction was associated with improvement in proteinuria.

• Rates of serious adverse events, including infections, were similar in both groups. Neutropenia, leucopenia, and hypotension occurred more frequently in the rituximab group. Two deaths occurred, both in the rituximab group, and they were considered to be unrelated to study drug.

The authors note that the study did not demonstrate a statistically significant difference between patients treated with rituximab and patients treated with placebo, although there were more partial responses in the rituximab group. They discuss possible reasons for the results shown, including that previous research in this area has focused on patients who a refractory to standard therapies, such as MMF and cyclophosphamide.

The authors conclude, “Although rituximab therapy led to more responders and greater reductions in anti-dsDNA and C3/C4 levels, it did not improve clinical outcomes after 1 year of treatment. The combination of rituximab with MMF and corticosteroids did not result in any new or unexpected safety signals.”