Rituximab in Refractory Lupus Nephritis

Linking up nicely with Nate’s rituximab post from this Tuesday, I wanted to mention a patient with lupus nephritis whom I saw in clinic this week. She had had horrendous renal disease, as seen on the three kidney biopsies she needed over the course of her illness. She failed to achieve remission despite multiple courses of steroids, cytoxan etc, but had the most remarkable response rituximab: complete remission after 2 doses, with a completely bland urinary sediment and a serum creatinine of 0.6 mg/dL one year out. I should also mention that she is now on maintenance MMF. Her case raises a few important questions; I used this review to try and answer some of them.


What’s the evidence for using Rituximab in refractory Lupus Nephritis?
To date, there is published data from over 20 studies, comprising 300 patients, of cases of refractory lupus or lupus nephritis treated with rituximab, with reported response rates of around 75%. However, positive reporting bias is a real concern, and no randomized trials in renal disease exist.

She continues to have very active serology; what does this mean?
Autoantibody levels in lupus and vasculitis do not predict relapse very well in general. The published studies report that responders will typically demonstrate a fall in anti–double-stranded DNA antibodies, and a correction of complement depletion. So, they appear to have more of a role in predicting response to treatment

She has had 2 doses of rituximab so far, without complication. Should she receive a third?
This patient has now been in remission for over 1 year. However, I’m concerned about the possibility of an impending relapse. Relapses are reported as occurring after an average of 10 to 13 months, although some patients maintain remission for several years. Also, her peripheral B cells (CD19+ or CD20+ lymphocytes) have recently recovered. Patients who fail to achieve depletion tend to have poor or no clinical response, whereas prolonged B cell depletion is associated with a prolonged clinical response. Protocol re-treatment at 4- or 6-mo intervals is under evaluation, so for now there is no good answer to this question.