Responsiveness to anti-tumour necrosis factor alpha therapy is related to pre-treatment tissue inflammation levels in rheumatoid arthritis patients.
OBJECTIVE
The response of rheumatoid arthritis (RA) patients to treatment with neutralising antibodies to tumour necrosis factor alpha (TNFalpha) is highly variable. The underlying mechanism for therapy responsiveness is currently unknown. We therefore evaluated the relationship between baseline molecular profiles of synovial tissues from RA patients and the clinical response to treatment with infliximab.


METHODS
Synovial biopsies were obtained by arthroscopy from 18 RA patients with active disease (28 joint count Disease Activity Score (DAS28) > or = 3.2) before initiation of treatment with infliximab. All patients were on stable methotrexate treatment. Clinical response at 16 weeks was defined as a reduction in DAS28 of > or = 1.2, non-response as reduction in DAS28 < 1.2. Large-scale gene expression profiling using microarrays was performed on synovial tissue samples. To identify biological processes in synovial biopsies that could discriminate between responders and non-responders, we performed pathway analysis on the expression profiles.


RESULTS
A total of 12 patients responded to therapy, while 6 patients failed to fulfil the response criteria. We identified several biological processes, related to inflammation, which were up-regulated in patients who responded to therapy, compared to those who did not show clinical improvement.


CONCLUSIONS
These results indicate that patients with a high level of tissue inflammation are more likely to benefit from anti-TNFalpha treatment.
VU University Medical Centre, Department of Molecular and Cellular Biology & Immunology, C262, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. t.vanderpouwkraan@vumc.nl
T C
TC
van der Pouw Kraan
C A
CA
Wijbrandts
L G
LG
van Baarsen
F
F
Rustenburg
J M
JM
Baggen
C L
CL
Verweij
P P
PP
Tak
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001665:Binding Sites; D001706:Biopsy; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008727:Methotrexate