Journal
RHEUMATOLOGY
Volume 50, Issue 2, Pages 283-292Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/keq344
Keywords
Rheumatoid arthritis; Biologics; Biomarkers; Personalized medicine; Pharmacogenomics; Predictive markers
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Funding
- French Ministry for Research
- Arthritis Foundation
- French Society of Rheumatology
- Amgen France
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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 epsilon 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-1 beta. Conclusion. 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).
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