Safety and efficacy of tumor necrosis factor α blockade in systemic lupus erythematosus: An open-label study
Article first published online: 8 OCT 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 10, pages 3161–3169, October 2004
How to Cite
Aringer, M., Graninger, W. B., Steiner, G. and Smolen, J. S. (2004), Safety and efficacy of tumor necrosis factor α blockade in systemic lupus erythematosus: An open-label study. Arthritis & Rheumatism, 50: 3161–3169. doi: 10.1002/art.20576
- Issue published online: 8 OCT 2004
- Article first published online: 8 OCT 2004
- Manuscript Accepted: 13 JUL 2004
- Manuscript Received: 8 JAN 2004
To investigate the safety of therapeutic tumor necrosis factor α (TNFα) blockade in patients with systemic lupus erythematosus (SLE), in whom this proinflammatory cytokine is significantly increased and may be involved in the disease pathogenesis.
In an open-label study, 6 patients with moderately active SLE (4 with nephritis and 3 with arthritis refractory to other therapies) were given 4 300-mg doses of infliximab, a chimeric anti-TNFα antibody, in addition to immunosuppression with azathioprine or methotrexate.
The only significant adverse events observed were urinary tract infection in 3 patients, 1 of which was accompanied by Escherichia coli bacteremia, and a prolonged febrile episode of putatively viral origin in 1 of them. These patients had similar infectious conditions in the past. In none of the patients was it necessary to terminate the treatment prematurely. Levels of antibodies to double-stranded DNA and cardiolipin increased in 4 patients each, but this was not associated with a decrease in serum complement levels, with vascular events, or with flares. In contrast, disease activity declined during therapy. All 3 patients with joint involvement experienced remission of arthritis, which relapsed 8–11 weeks after the last infliximab infusion. In the 4 patients with lupus nephritis, proteinuria decreased significantly within 1 week after initiation of therapy and was diminished by ≥60% within 8 weeks, remaining at low levels until the end of the observation period (at least several months).
Infliximab did not lead to adverse events related to an increase in SLE activity, although autoantibodies to double-stranded DNA and cardiolipin increased, as expected. This finding, coupled with the clinical improvement in the inflammatory manifestations of the disease, indicates that further study in larger controlled trials is warranted.