Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease in which B-lymphocytes play an pivotal role. We have induced B cell depletion utilising a combination of rituximab, cyclophosphamide, and steroids given intravenously. This regime depletes B-lymphocytes in the peripheral blood. We now report a long-term follow up study of 24 patients who had failed conventional immunosuppression.
24 patients (22 female, 2 male, mean age 30 years, range 17–49) were treated. The mean disease duration was 7.9 years (range 1–18 years). Twelve of the patients were Caucasian, 8 Afro-Caribbean and 4 of Asian origin. The majority of these patients were treated with two infusions of 1 g rituximab, two infusions of 750 mg cyclophosphamide and two infusions of methylprednisolone 100 mg. Patients were allowed to continue on prednisolone and hydroxychloroquine. Only 2 patients continued on azathioprine.
The global BILAG score reduced from a median of 13.9 at baseline (SEM = 1.18) to 5 (SD = 1) at three months and 5.0 (SEM = 0.6) at six months. 23/24 patients achieved depletion in the peripheral blood (CD19+ <0.005/l) and there was improvement in BILAG score in each of the eight systems or organs. The period of B lymphocyte depletion ranged from three to eleven months except in 1 patient who remains depleted for > 4 years. Whereas the mean total serum immunoglobulins levels remained within the normal range, analysis of the serum C3 levels (in 21 patients) showed a statistically significant improvement (P < 0.0005) at six months as did anti-dsDNA binding (P < 0.02). 1 patient, scored the most active (BILAG global score 45) died of sepsis five months after the infusion having shown a considerable improvement at three months. 1 patient had a severe infusion reaction. No other serious adverse events were observed. 7 patients have now been retreated, 1 on two further occasions. 1 patient failed to deplete on retreatment due to a documented specific HACA response.
B lymphocyte depletion therapy utilising rituximab has been shown to be an effective treatment for active refractory lupus. Our data further indicate that both clinical and serological improvement is seen in the majority of these patients. The efficacy and apparent safety of this treatment in established cases of lupus indicate the possible use of this treatment in patients earlier in the course of their disease.