Abstract | OBJECTIVE: Safer and more effective therapies are needed for the treatment of systemic lupus erythematosus (SLE). B lymphocytes have been shown to play fundamental pathogenic roles in SLE, and therefore, elimination of B cells with the use of rituximab may represent a new therapy for SLE. METHODS: A phase I/II dose-escalation trial of rituximab added to ongoing therapy in SLE was conducted. Rituximab was administered as a single infusion of 100 mg/m2 (low dose), a single infusion of 375 mg/m2 (intermediate dose), or as 4 infusions (1 week apart) of 375 mg/m2 (high dose). CD19+ lymphocytes were measured to determine the effectiveness of B cell depletion. The Systemic Lupus Activity Measure (SLAM) score was used as the primary outcome for clinical efficacy. RESULTS:
Rituximab was well tolerated in this patient population, with most experiencing no significant adverse effects. Only 3 serious adverse events, which were thought to be unrelated to rituximab administration, were noted. A majority of patients (11 of 17) had profound B cell depletion (to <5 CD19+ B cells/microl). In these patients, the SLAM score was significantly improved at 2 and 3 months compared with baseline (P = 0.0016 and P = 0.0022, respectively, by paired t-test). This improvement persisted for 12 months, despite the absence of a significant change in anti-double-stranded DNA antibody and complement levels. Six patients developed human antichimeric antibodies (HACAs) at a level > or =100 ng/ml. These HACA titers were associated with African American ancestry, higher baseline SLAM scores, reduced B cell depletion, and lower levels of rituximab at 2 months after initial infusion. CONCLUSION:
Rituximab therapy appears to be safe for the treatment of SLE and holds significant therapeutic promise, at least for the majority of patients experiencing profound B cell depletion. Based on these results, controlled trials of rituximab appear to be warranted.
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Authors | R John Looney, Jennifer H Anolik, Debbie Campbell, Raymond E Felgar, Faith Young, Lois J Arend, James A Sloand, Joseph Rosenblatt, Iñaki Sanz |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 50
Issue 8
Pg. 2580-9
(Aug 2004)
ISSN: 0004-3591 [Print] United States |
PMID | 15334472
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- Rituximab
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Topics |
- Adult
- Antibodies, Monoclonal
(administration & dosage, adverse effects, pharmacokinetics)
- Antibodies, Monoclonal, Murine-Derived
- B-Lymphocytes
- Female
- Humans
- Lupus Erythematosus, Systemic
(therapy)
- Lymphocyte Depletion
- Male
- Middle Aged
- Rituximab
- Treatment Outcome
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