Impact of three anti-TNFalpha biologics on existing and emergent autoimmunity in rheumatoid arthritis and spondylarthropathy patients.
OBJECTIVE
The objective of this study was to analyze the effects of 3 anti-TNFalpha agents on markers of autoimmunity in rheumatoid arthritis (RA) and spondylarthropathy (SPA) patients.


METHODS
First-time anti-TNFalpha biologics (infliximab, etanercept, or adalimumab) were prescribed to 156 RA and 95 SPA (58 ankylosing spondylarthritides, 37 psoriatic arthritides). During 1-2 years of follow-up, clinical, biological [antinuclear (ANA) and anti-double-stranded (dsDNA) antibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP) for RA], and therapeutic data were collected biannually.


RESULTS
ANA appeared or ANA and anti-dsDNA titers increased significantly (P < 0.001) more under infliximab than etanercept in both rheumatisms and than adalimumab in RA patients. During the 2-year follow-up, ANA appeared more in RA patients taking adalimumab than etanercept (P = 0.003), but independently of the anti-TNFalpha used; anti-dsDNA titers rarely became positive. Under etanercept or infliximab, ANA and anti-dsDNA were not influenced by the underlying pathology nor were they affected by infliximab intensification over 18 months. Only one case of cutaneous lupus was observed in a patient having IgG anti-dsDNA. The therapeutic responses were independent of ANA and anti-dsDNA titers for all rheumatisms and biologics. In RA patients, RF titers, but not anti-CCP levels, declined with the therapeutic response for all biologics.


CONCLUSIONS
This is the first study that has evaluated the impact of three TNFalpha blockers on ANA and anti-dsDNA antibodies in RA and SPA patients. Autoimmunity was more induced with infliximab than etanercept and to a lesser degree to adalimumab but, more importantly, this emergent autoimmunity was exceptionally associated to clinical manifestations of lupus.
Bacquet-Deschryver
H
H
Department of Rheumatology, Rouen University Hospital & Inserm U905 (IFRMP 23), Institute for Biomedical Research, University of Rouen, 76031 Rouen Cedex, France.
Jouen
F
F
Quillard
M
M
Ménard
J F
JF
Goëb
V
V
Lequerré
T
T
Mejjad
O
O
Daragon
A
A
Tron
F
F
Le Loët
X
X
Vittecoq
O
O
D000068879:Adalimumab; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012720:Severity of Illness Index; D025242:Spondylarthropathies / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001323:Autoantibodies; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept