A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus.
Although corticosteroids and immunosuppressants are widely used for the treatments of systemic lupus erythematosus (SLE), safer and more effective therapies are prerequisite. We and others have reported that anti-CD20 antibody rituximab targeting B cells are effective for refractory SLE and, therefore, safety and clinical efficacy of rituximab in SLE was evaluated by a multicenter phase I/II clinical trial. An open-label, multicenter study of 15 patients with active and refractory SLE (total British Isles Lupus Assessment Group [BILAG] score 8 to 17) was conducted. Rituximab was administered to 5 SLE patients as 4 infusions of 500 mg/body every week and to 10 SLE patients as 2 infusions of 1000 mg/body every other week. Assessment of safety, infusion reactions and adverse effects was used as the primary outcome for clinical tolerability and was evaluated by 28 weeks. Rituximab was well tolerated, with most experiencing no significant adverse effects. B cells rapidly reduced in all patients and remained low until 6 months post-treatment. Four patients developed human antichimeric antibodies without affecting efficacy of rituximab. Changes in routine safety laboratory tests clearly related to rituximab were not observed. Nine among 14 evaluable patients achieved the major or partial clinical response of BILAG score and prednisolone dose significantly decreased at the 28 weeks. Rituximab therapy appears to be safe for the treatment of active SLE patients and holds significant therapeutic promise, at least for the majority of patients experiencing profound B-cell depletion.
Tanaka
Yoshiya
Y
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan. tanaka@med.uoeh-u.ac.jp
Yamamoto
Kazuhiko
K
Takeuchi
Tsutomu
T
Nishimoto
Norihiro
N
Miyasaka
Nobuyuki
N
Sumida
Takayuki
T
Shima
Yoshihito
Y
Takada
Kazuki
K
Matsumoto
Isao
I
Saito
Kazuyoshi
K
Koike
Takao
T
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001402:B-Lymphocytes; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab