Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra)

• Published in: Rheumatology Vol. 50; no. 2; pp. 283 - 292
• Main Authors: BANSARD, Carine, LEQUERRE, Thierry, LE LOËT, Xavier, SALIER, Jean-Philippe, DERAMBURE, Céline, VITTECOQ, Olivier, HIRON, Martine, DARAGON, Alain, POUPLIN, Sophie, DAVEAU, Maryvonne, BOYER, Olivier, TRON, François
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-02-2011; Oxford University Press (OUP)
• Subjects: Adult; Aged; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Biochemistry, Molecular Biology; Biological and medical sciences; Diseases of the osteoarticular system; Drug Therapy, Combination; Female; Gene Expression Profiling; Genomics; Humans; Immunomodulators; Inflammatory joint diseases; Interleukin 1 Receptor Antagonist Protein - administration & dosage; Life Sciences; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Pharmacology. Drug treatments; Treatment Outcome; Validation Studies as Topic; Immunopathology; Diseases of the osteoarticular system; Rheumatology; Biological marker; Autoimmune disease; Inflammatory joint disease; Predictive markers; Personalized medicine; Immunomodulator; Medicine; Chronic; Rheumatoid arthritis; Biologics; Biomarkers; Predictive factor; Anakinra; Pharmacogenomics
• ISSN: 1462-0324; 1462-0332; 1460-2172
• DOI: 10.1093/rheumatology/keq344

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.
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.
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.
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).