B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus.
OBJECTIVE
To determine the safety and efficacy of B lymphocyte depletion therapy in patients with refractory childhood-onset systemic lupus erythematosus (SLE).


METHODS
Seven patients (4 of whom were female), ages 7.7-16.1 years (median 14.8 years) with active SLE that was resistant to standard immunosuppressive agents were treated with B cell depletion. During a 2-week period, patients received two 750-mg/m2 intravenous infusions of rituximab, with intravenous cyclophosphamide (if they had not previously received this treatment) and high-dose oral corticosteroids.


RESULTS
Patients were followed up for a median of 1.0 years, and no serious adverse effects were noted. In all patients, the clinical symptoms and signs for which rituximab therapy was initiated were improved. There was significant improvement in the British Isles Lupus Assessment Group global scores, from a median score of 22 (range 14-37) at baseline to a median score of 6 (range 4-11) at followup (P = 0.002). In 2 patients with severe multisystem and life-threatening disease unresponsive to standard therapy (including plasma exchange), renal replacement therapy was successfully withdrawn following B cell depletion therapy. These 2 patients have subsequently shown further significant improvement in renal function and proteinuria.


CONCLUSIONS
This open-label study demonstrates that targeted B cell depletion therapy can be a safe and efficacious addition to therapy with standard immunosuppressive agents in patients with refractory childhood SLE. The drugs used for treatment of childhood SLE need to be the most effective, least toxic agents, allowing normal growth and development.
Marks
Stephen D
SD
Department of Paediatric Nephrology, Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK. s.marks@ich.ucl.ac.uk
Patey
Sue
S
Brogan
Paul A
PA
Hasson
Nathan
N
Pilkington
Clarissa
C
Woo
Patricia
P
Tullus
Kjell
K
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D007668:Kidney / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D010865:Pilot Projects; D000069283:Rituximab; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide