Adding rituximab to mycophenolate mofetil and corticosteroids does not improve outcomes in patients with lupus nephritis (LN), according to a study.

As part of the Lupus Nephritis Assessment with Rituximab (LUNAR) trial, American and Mexican investigators led by Brad H. Rovin, MD, Director of Nephrology at the Ohio State College of Medicine in Columbus, Ohio, studied 144 patients (aged 16-75 years) with class III or IV LN who were taking mycophenolate mofetil (MMF) and corticosteroids. They randomized 72 subjects to receive add-on therapy with 1000 mg rituximab on days 1, 15, 168, and 182, and 72 to receive placebo on the same schedule.

Rituximab treatment was not associated with a higher rate of complete or partial renal responses at the end of the study, with a 56.9% rate compared to 45.8% for placebo, the researchers reported online ahead of print in Arthritis & Rheumatism.

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“At this time we cannot recommend the addition of rituximab to MMF for the initial therapy of proliferative lupus nephritis,” Dr. Rovin concluded. “We suspect that there are patients who may benefit from rituximab, but we still need to develop methods to identify who they are.”

LN can occur in up to 50% of patients with systemic lupus erythematosus and is not associated with a good prognosis. Furthermore, standard proliferative treatment of LN achieves renal response rates of only 50%-80%, and many patients achieve partial rather than full remission. Because B cells have been shown to play a key role in LN, and because rituximab depletes CD20-positive B cells while sparing stem cells and plasma cells, Dr. Rovin’s team opted to study rituximab as add-on LN therapy.

MMF was first given at 1.5 g/day in three divided doses and increased, as tolerated, to 3 g/day by week 4 and continued until at least week 52. In addition, patients received oral prednisone 0.75 mg/kg/day up to a maximum of 60 mg until day 16, and were tapered to 10 mg/day or less by week 16. Other immunosuppressive agents were not permitted.

Rituximab depleted peripheral CD19+ B cells in 98.6% of rituximab-treated patients (71/72). The study, however, demonstrated no significant difference in the rate of the primary endpoint—complete and partial renal responses—between the two groups. Moreover, the small difference in the rate was primarily due to more partial responses with rituximab.

Rates of serious adverse events including infections were similar in both groups. Neutropenia, leucopenia, and hypotension were more frequent in the rituximab group.

“Further randomized trials with rituximab can help clarify the role of rituximab in LN treatment, including whether rituximab should be used in place of MMF or cyclophosphamide instead of as add-on therapy, and whether rituximab has a role in salvaging patients with refractory LN,” Dr. Rovin stated.

“These studies remain to be set up, but the results of an ongoing U.K. investigation of rituximab as a primary therapy will be reported soon; results presented in abstract form at scientific meetings indicate this approach has promise.”