Earlier Rituximab Better for Lupus Nephritis Patients

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ATLANTA—Lupus nephritis patients who receive rituximab earlier in the course of their disease rather than later have better outcomes, new findings suggest.

“We have been trying to use rituximab in a different way,” said David Isenberg, MD, Academic Director of Rheumatology at University College London, London, England.

Over the past 10 years, lupus nephritis patients usually have been treated with rituximab at the end of their disease course. “They have failed conventional immunosuppression and failed steroids and they are given rituximab because there is really nowhere else to go with them,” Dr. Isenberg said. “Now, we are starting to treat patients with lupus with rituximab at the time of diagnosis and get them better without the side effects that come with steroids.”

Patients given rituximab at the time of diagnosis tend to have a substantial reduction in the amount of oral steroids normally required during the first six months of treatment. This is important, Dr. Isenberg said, because it shows that early use of rituximab can achieve the same outcomes without patients experiencing the serious adverse side effects associated high doses of oral steroids.

Traditional therapies for lupus nephritis have been limited in their ability to achieve rapid disease control and damage prevention. However, rituximab has been widely reported to be effective in treating renal disease flares. In 2009, Dr. Isenberg and his colleagues published data (Lu et al. Arthritis Rheum. 2009;61:482-487) indicating that the clinical value of rituximab is related to the period of B-cell depletion.

The study included 38 lupus nephritis patients treated between July 2001 and December 2009 at the University College Hospital London. All had a minimum of 12 months of follow-up. The researchers evaluated patients at baseline and six months after the start of rituximab treatment.  For this investigation, response to treatment was defined as an absolute CD19 cell count below 0.005 x 109/L. The absence of these cells reflects the degree of success in removing the B lymphocytes. Values above this were considered evidence of repopulation.

The researchers found that after the first cycle of rituximab, 34 patients (89%) were successfully depleted of CD19 cells. However, after six months, only 11 patients (32%) remained depleted.  The investigators compared the depleted versus the repopulated group and found no differences in terms of classical disease activity markers: erythrocyte sedimentation rate, anti-dsDNA antibodies, and serum levels of the C3 component of the complement system of the blood. ESR is a widely used nonspecific marker of inflammation. Anti-dsDNA antibodies are antibodies most closely associated with active lupus. Low serum C3 levels are linked to active lupus.

In addition, other serological markers such as the anti-C1q antibodies, ENAab and anti-cardiolipin antibodies showed no association with depletion status.

Analysis of ENAab subgroups revealed that patients who tested negative for anti-Sm antibodies tended to remain depleted at six months. Anti-Sm antibodies are a lupus-specific marker found in about 10% of white lupus patients and 30% of black lupus patients. Baseline proteinuria and serum creatinine level failed to influence response. In terms of ethnicity, patients of Afro-Caribbean origin were more likely to have repopulated at six months than patients of other ethnic groups.

The researchers presented their findings at the American College of Rheumatology annual meeting.

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