ORIGINAL ARTICLE

A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus

Authors

Yoshiya Tanaka¹, Kazuhiko Yamamoto², Tsutomu Takeuchi³, Norihiro Nishimoto⁴, Nobuyuki Miyasaka⁵, Takayuki Sumida⁵, Yoshihito Shima⁴, Kazuki Takada⁵, Isao Matsumoto⁶, Kazuyoshi Saito1 and Takao Koike⁷

1. First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan
2. Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
3. Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
4. Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
5. Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
6. Department of Clinical Immunology, University of Tsukuba, Ibaraki, Japan
7. Department of Medicine II, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

Received:

29 January 2007

Accepted:

26 February 2007

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Abstract

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 500mg/body every week and to 10 SLE patients as 2 infusions of 1000mg/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.

Key words

B cells - CD20 - Monoclonal antibody - Rituximab - Systemic lupus erythematosus (SLE)