Results a of preliminary study of rituximab for difficult NPSLE
- Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system
- Annals of the Rheumatic Diseases, Volume 66, Number 4, April 2007, pp. 470 – 475
What is the topic?
Lupus may affect the central nervous system (NPSLE), with estimates varying widely (from 12to to 75%) for the number of lupus patients who experience minor or moderate flares in the nervous system. Serious lupus flares in the brain are rare. Symptoms of NPLSE include headaches, confusion or thinking disorders (often referred to "lupus fog"), mood changes, problems with vision, and seizures. Depending on the symptoms, a variety of medications are available to treat lupus-related nervous system disorders, and for many lupus patients, nervous system involvement is completely reversible. However, some lupus patients with NPSLE do not respond to the current treatments, and in rare cases the complications can be quite serious.
What did the researchers hope to learn?
Researchers in Japan sought to determine if rituximab (trade name: Rituxan®) could be an effective treatment for patients with significant NPSLE that had failed to respond to the conventional lupus treatments. Rituximab is a monoclonal antibody that has been approved for use in treating rheumatoid arthritis and other autoimmune diseases.
Who was studied?
The researchers studied 10 patients who had NPSLE that had not improved with aggressive immunosuppressive treatment, either intravenous cyclophosphamide, cyclosporine A, plasma exchange, or immunoadsorption.
How was the study conducted?
Each of the 10 patients studied was given rituximab as an infusion in a vein. Doses differed as did the number of times the patients were treated, with some patients receiving rituximab twice a week for two weeks, others once a week for four weeks, another one every other week for four weeks; one patient had only one dose of the drug. Patients were then followed for up to 45 months. At the start of the rituximab treatment, patients were also treated with low-to-moderate doses of steroids and continued to use this treatment after they received the rituximab. One patient was also allowed to continue taking an immunosuppressant.
What did the researchers find?
The researchers found that rituximab was effective in treating the NPSLE symptoms in all 10 patients. In particular, patients who had mental confusion at the start of the study improved rapidly, within a matter of days. Rituximab also improved mood disorders within a few weeks or months after treatment. Many of these improvements persisted for months, and some of the patients remained symptom-free at the end of the follow-up period. However, some of the patients relapsed after long-term remission, requiring either retreatment with rituximab, increased corticosteroids, or immunosuppressants. Several patients also developed infections, which may have been related to the suppression of the immune system resulting from the use of rituximab and/or the other treatments they received.
What were the limitations of the study?
This is a very preliminary report and no final conclusions can be drawn from it. This study only involved 10 patients, and their clinical symptoms were diverse. Some of the patients, despite a history of not responding to past treatments, might have gotten better on the steroids alone. Further research with a larger number of participants is definitely called for. With more studies involving greater numbers of patients and the ability to compare rituximab to alternative treatments, researchers may be able to determine whether this treatment really is effective and also examine the effect of rituximab on particular symptoms of NPSLE, and also try to determine factors that affect which patients the treatment might or might not work for.
What do the results mean for you?
This very preliminary study suggests that Rituximab is a good candidate to study further as a potential new therapy for NPSLE lupus -- and one that may work when other treatments have failed. This study also suggests the possibility that NPSLE patients will respond to rituximab both rapidly and over long periods of time, although larger studies comparing Rituximab to alternative treatments would be needed to determine if this can be verified.