Study on B-cell depletion therapy

36% of patients with refractory systemic lupus erythematosus (SLE or lupus) remain well after undergoing B-cell depletion therapy (BCDT) without needing further standard immunosuppressive agents, according to a study presented at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain.

Overactive B-cells are commonly found in patients with SLE and reducing the number of B-cells in the system by BCDT has been suggested as a promising therapy for SLE patients who are unresponsive to other treatments.

In this study, initiated in 2000, patients with refractory SLE were treated with BCDT (based on rituximab) using a combination protocol with cyclophosphamide and steroids. Of the 33 patients who had a minimum of 6 months follow-up duration at the time of analysis (mean duration 37 months, range 6-79), 12 patients remained well. Median duration of B-cell depletion was 4 months (range 2-15), with 2 patients remaining depleted at time of analysis (73 and 8 months respectively). B-cell depletion was beneficial clinically, with a decrease of median global BILAG scores (clinical activity index see Editors note) from 13 to 5 when measured between 5 and 8 months p<0.0001).

Autoantibody profiling was also examined during the study as a possible predictor of flare of disease. Patients with low baseline serum C3 (84%) had a shorter time to flare post-BCDT (a lower level is a strong indicator of high levels of disease activity) and patients with anti-ENA antibodies notably anti-Sm antibodies (63%) were more likely to flare at any time after BCDT with an odds ratio (OR) of 6 (p=0.03).

Co-author of the paper, Professor David Isenberg, from University College London in the United Kingdom, commented: Although double blind trials are awaited, our results are encouraging. They show that B-cell depletion therapy is a promising therapeutic option for lupus patients who have a historically difficult to treat disease, and potentially could minimise the need for continuous immunosuppressive therapy. Through monitoring the autoantibody profile of these patients we have seen a strong association with disease activity post-BCDT, offering us valuable insight for future patient identification strategies.

Of the 20 patients who experienced flares after receiving BCDT, 11 flared between 6-12 months post-BCDT, with a mean time to flare (TTF) of 10 months post-BCDT. Thirteen patients have been retreated with at least another cycle of rituximab. In terms of B-cell depletion, one patient in the study sample did not deplete at all.

The study concludes that the long term safety profile of B-cell depletion therapy is so far favourable, though ongoing vigilance is recommended. Serious adverse events included reports of pneumococcal sepsis, severe serum sickness reaction and seizure related to hyponatriaemia. Two patient deaths occurred during the follow up assessment period.