An open study of B lymphocyte depletion in systemic lupus erythematosus.
OBJECTIVE
To gain preliminary evidence for the safety and efficacy of B lymphocyte depletion therapy in refractory systemic lupus erythematosus (SLE).


METHODS
Six female patients with active SLE, resistant to standard immunosuppressive therapy, were treated on an open-label basis. During a 2-week period, each patient received two 500-mg infusions of rituximab, two 750-mg infusions of cyclophosphamide, and high-dose oral corticosteroids.


RESULTS
No significant adverse events were observed during followup. Patient 1 had not improved at 3 months but was then lost to followup. At 6 months, all 5 remaining patients had improved, as evidenced by improvement in British Isles Lupus Assessment Group global scores, from a median of 14 (range 9-27) at baseline to a median of 6 (range 3-8) at 6 months. Manifestations of SLE such as fatigue, arthralgia/arthritis, and serositis responded particularly well to this protocol. Hemoglobulin levels increased in patients 2, 3, 5, and 6. The erythrocyte sedimentation rate decreased in patients 2, 3, 4, and 5 and was stable in patient 1. In patients 4 and 5, the urinary protein-to-creatinine ratio decreased significantly. C3 serum levels increased in all 5 patients who had low levels at baseline; in two of these patients, patients 2 and 5, C3 values were normal at 6 months. The variation in the level of anti-double-stranded DNA antibody was different in individual patients.


CONCLUSIONS
This study provides sufficient evidence for the safety and possible efficacy of B lymphocyte depletion therapy in SLE to justify a formal controlled trial.
Leandro
Maria J
MJ
Rheumatology, Middlesex Hospital, University College, 4th Floor Arthur Stanley House, 40-50 Tottenham Street, London W1T 4NJ, UK. maria.leandro@ucl.ac.uk
Edwards
Jonathan C
JC
Cambridge
Geraldine
G
Ehrenstein
Michael R
MR
Isenberg
David A
DA
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001402:B-Lymphocytes / Q000276:immunology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D011239:Prednisolone