An eight-gene blood expression profile predicts the response to infliximab in rheumatoid arthritis.
BACKGROUND
TNF alpha blockade agents like infliximab are actually the treatment of choice for those rheumatoid arthritis (RA) patients who fail standard therapy. However, a considerable percentage of anti-TNF alpha treated patients do not show a significant clinical response. Given that new therapies for treatment of RA have been recently approved, there is a pressing need to find a system that reliably predicts treatment response. We hypothesized that the analysis of whole blood gene expression profiles of RA patients could be used to build a robust predictor to infliximab therapy.


RESULTS
We performed microarray gene expression analysis on whole blood RNA samples from RA patients starting infliximab therapy (n = 44). The clinical response to infliximab was determined at week 14 using the EULAR criteria. Blood cell populations were determined using flow cytometry at baseline, week 2 and week 14 of treatment. Using complete cross-validation and repeated random sampling we identified a robust 8-gene predictor model (96.6% Leave One Out prediction accuracy, P = 0.0001). Applying this model to an independent validation set of RA patients, we estimated an 85.7% prediction accuracy (75-100%, 95% CI). In parallel, we also observed a significantly higher number of CD4+CD25+ cells (i.e. regulatory T cells) in the responder group compared to the non responder group at baseline (P = 0.0009).


CONCLUSIONS
The present 8-gene model obtained from whole blood expression efficiently predicts response to infliximab in RA patients. The application of the present system in the clinical setting could assist the clinician in the selection of the optimal treatment strategy in RA.
Grup de Recerca de Reumatologia, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Antonio
A
Julià
Alba
A
Erra
Carles
C
Palacio
Carlos
C
Tomas
Xavier
X
Sans
Pere
P
Barceló
Sara
S
Marsal
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D020869:Gene Expression Profiling; D006801:Humans; D000069285:Infliximab; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015203:Reproducibility of Results; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D053645:Interleukin-2 Receptor alpha Subunit; D000069285:Infliximab