Prospective cohort study of effects of infliximab on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis.
BACKGROUND
Antibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFalpha antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy.


METHODS
Thirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined.


RESULTS
At baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly (p<0.001), whereas anti-CCP showed little change (p=0.053). ANA titres increased significantly (p<0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16-3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16-4.13]).


CONCLUSIONS
During infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.
Bruns
Alexandra
A
Rheumatology Department, Bichat Teaching Hospital, AP-HP, CHU Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Nicaise-Roland
Pascale
P
Hayem
Gilles
G
Palazzo
Elisabeth
E
Dieudé
Philippe
P
Grootenboer-Mignot
Sabine
S
Chollet-Martin
Sylvie
S
Meyer
Olivier
O
D000974:Antibodies, Antinuclear / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D000069285:Infliximab; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000097:blood*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; D000069285:Infliximab