Induction of autoantibodies during prolonged treatment with infliximab.
OBJECTIVE
To determine the frequency and correlates of autoantibody formation in patients with rheumatic diseases treated with infliximab in a routine clinical setting.


METHODS
All patients receiving at least 5 infusions of infliximab, and with anticipated continuation, were prospectively evaluated for the development of the following antibodies: antinuclear antibody (ANA), anti-DNA, anti-Sm, anti-RNP, anti-SSA and anti-SSB. Correlates with pharmacologic treatments, response to infliximab, and adverse events were assessed.


RESULTS
Seventy-six percent of 42 patients receiving prolonged treatment with infliximab developed new autoantibodies, and these persisted in 57%. The most common new autoantibody was ANA in 45%, followed by anti-DNA in 33%, anti-Sm in 31%, and anti-RNP in 29%. New autoantibody formation was associated with both a greater number of infusions (p = 0.015) and a higher total dose of infliximab infused (p = 0.047). No other treatment, disease characteristic, or loss of efficacy to infliximab discriminated between those developing antibodies compared to those without new antibody formation. No patient developed clinical signs of a new connective tissue disease.


CONCLUSIONS
Autoantibody formation is seen commonly in patients receiving prolonged treatment with infliximab. Concomitant immunosuppressive treatments did not preclude the formation of antibodies. The clinical significance of antibody formation remains to be determined.
Louis
Mariam
M
Division of Rheumatology, McGill University Health Centre at Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4.
Rauch
Joyce
J
Armstrong
Mary
M
Fitzcharles
Mary-Ann
MA
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D000069285:Infliximab