Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an open-label study.
OBJECTIVE
To investigate the safety of therapeutic tumor necrosis factor alpha (TNFalpha) blockade in patients with systemic lupus erythematosus (SLE), in whom this proinflammatory cytokine is significantly increased and may be involved in the disease pathogenesis.


METHODS
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-TNFalpha antibody, in addition to immunosuppression with azathioprine or methotrexate.


RESULTS
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 > or = 60% within 8 weeks, remaining at low levels until the end of the observation period (at least several months).


CONCLUSIONS
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.
Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Martin
M
Aringer
Winfried B
WB
Graninger
Günter
G
Steiner
Josef S
JS
Smolen
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy; D001323:Autoantibodies / Q000097:blood; D001379:Azathioprine / Q000008:administration & dosage; D016470:Bacteremia / Q000209:etiology; D002308:Cardiolipins / Q000276:immunology; D003165:Complement System Proteins / Q000032:analysis; D004247:DNA / Q000276:immunology; D004927:Escherichia coli Infections / Q000209:etiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D000069285:Infliximab; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008181:Lupus Nephritis / Q000188:drug therapy / Q000652:urine; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D012449:Safety; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D014552:Urinary Tract Infections / Q000209:etiology
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; D002308:Cardiolipins; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins; D004247:DNA; D000069285:Infliximab; D001379:Azathioprine; D008727:Methotrexate