Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7 yrs

To assess safety and efficacy of repeated B-cell depletion with rituximab in patients with rheumatoid arthritis (RA).

Thirty-seven patients with refractory RA entered into a programme of repeated B-lymphocyte depletion (up to 5 cycles, 89 cycles in total) with protocols based on the anti-CD20 monoclonal antibody, rituximab, have been observed over periods of >5 yrs (n = 22) or 3-5 yrs (n = 14).

Twenty two subjects have been followed up for >5 yrs. Average duration of benefit per cycle was 15 months (maximum 43 months), and time to re-treatment 20 months. Nineteen patients remain on the programme. Patients were withdrawn for lack of efficacy (n = 5), hypersensitivity infusion reaction (n = 1), brevity of response (n = 8), or occurrence of adverse respiratory events (n = 1). Sixteen major lower respiratory events occurred during the 180 patient-yrs of follow-up. Of these only one had low IgG. In patients receiving rituximab +/- cyclophosphamide (cy) carcinomata have developed as follows: breast (3, +cy), ovary (1, +cy), transitional cell (1, +cy), and renal cell (1, -cy). Falls in total immunoglobulin levels to below the normal range occurred in 12 patients for IgM (undetectable levels in three after repeated cycles), seven for IgG and one for IgA, not taking into account patients who started off with low immunoglobulin levels before the first cycle.

Repeated B-lymphocyte depletion over a 5-yr period appears to be an acceptable and relatively well-tolerated therapy in RA with a relatively high rate of continuation. Long-term effects on immunoglobulin levels require surveillance.