OBJECTIVES: 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. 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).
OBJECTIVES: 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. 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).
Authors: Ty M Thomson; Reynald M Lescarbeau; David A Drubin; Daphna Laifenfeld; David de Graaf; David A Fryburg; Bruce Littman; Renée Deehan; Aaron Van Hooser Journal: BMC Med Genomics Date: 2015-06-03 Impact factor: 3.063
Authors: C Derambure; G Dzangue-Tchoupou; C Berard; N Vergne; M Hiron; M A D'Agostino; P Musette; O Vittecoq; T Lequerré Journal: Arthritis Res Ther Date: 2017-05-25 Impact factor: 5.156
Authors: A N Burska; K Roget; M Blits; L Soto Gomez; F van de Loo; L D Hazelwood; C L Verweij; A Rowe; G N Goulielmos; L G M van Baarsen; F Ponchel Journal: Pharmacogenomics J Date: 2014-03-04 Impact factor: 3.550