Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra).
OBJECTIVE
The overall non-response rate to biologics remains 30-40% for patients with RA resistant to MTX. The objective of this study was to predict responsiveness to the anakinra-MTX combination by peripheral blood mononuclear cell gene profiling in order to optimize treatment choice.


METHODS
Thirty-two patients treated with anakinra (100 mg/day s.c.) and MTX were categorized as responders when their 28-joint DAS (DAS-28) had decreased by ≥1.2 at 3 months. Pre-treatment blood samples had been drawn.


RESULTS
For seven responders and seven non-responders, 52 microarray-identified mRNAs were expressed as a function of the response to treatment, and unsupervised hierarchical clustering correctly separated responders from non-responders. The levels of seven of these 52 transcripts, as assessed by real-time, quantitative RT-PCR, were able to accurately classify 15 of 18 other patients (8 responders and 10 non-responders), with 87.5% specificity and 77.8% negative-predictive value for responders. Among the 52 genes, 56% were associated with IL-1β.


CONCLUSIONS
This predictive gene expression profile was obtained with a non-invasive procedure. After further validation in other cohorts of patients, it could be proposed and used on a large scale to select likely RA responders to combined anakinra-MTX. Trial registration. Clinical Trials; NCT00213538 (http://www.clinicaltrials.gov).
Department of Rheumatology, University of Rouen, 76031 Rouen Cedex, France.
Carine
C
Bansard
Thierry
T
Lequerré
Céline
C
Derambure
Olivier
O
Vittecoq
Martine
M
Hiron
Alain
A
Daragon
Sophie
S
Pouplin
Maryvonne
M
Daveau
Olivier
O
Boyer
François
F
Tron
Xavier
X
Le Loët
Jean-Philippe
JP
Salier
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D016896:Treatment Outcome; D054928:Validation Studies as Topic
D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D008727:Methotrexate