B-lymphocytes (BL) play a critical role in Systemic Lupus Erythematosus (SLE). BL depletion therapy still remains an attractive option, despite the disappointing results of RCTs.
Methods
Twelve SLE patients [2 males, mean age 43.8 yrs (29-54)] with polyarthralgia and multiorgan involvement including class IV or III/V (ISN/RPS) glomerulonephritis (9 cases), skin lesions (9 cases, with necrotizing ulcers in3), polyneuropathy (7cases, with CNS involvement in 2), lymphoadenopathy (6) e polysierositis (5) have been treated withan IBLD protocol for intolerance to conventional immunosuppressive therapy (6 cases) or as a front line therapy (6 cases). Protocol: Rituximab 375 mg/sm on days 1, 8, 15, 22, and 2 more doses after one and two months, associated with 2 IV administrations of 10 mg/kg of cyclofosfamide, and 3 infusions of methylprednisolone (15 mg/kg) followed by oral prednisone (0.8 mg/die, rapidly tapered to 5 mg/day in 10 weeks).
No further immunosuppressive maintenance therapy has been given.
Results
IBLD obtained a complete depletion of CD20+ BL for 12-18 months. Patients had been followed-up for 48.9 (25-93) months. A significant decreases (p<0.05) were found in the levels of ESR (baseline mean value: 54.2 mm; 3 months: 33; end of follow-up: 14.9), anti-dsDNA antibodies (baseline: 192 U; 3 months: 112; end of follow-up: 17) and proteinuria (baseline: 4.9 g/24 hours; 3 months: 0.97; end of follow-up: 0.22). Conversely, C4 values (baseline 11 mg/dl) significantly increased (p<0.05) after 3 months (22 mg/dl) and at the end of the follow-up (20 mg/dl). Three patients relapsed after 36, 41 and 72 months, respectively. They showed again a complete remission after retreatment over 13-48 months of observation.
Conclusions
These data confirm the opportunity to reconsider the regimens of BL depletion in the treatment of the most severe forms of SLE despite the disappointing results of RCTs. A promising role of Rituximab in protocols of “intensified induction therapy” in selected patients for whom avoiding immunosuppressive maintenance therapy is particularly appealing can be envisaged.