Abstract
BackgroundDespite the success of TNF-inhibitor therapy in rheumatoid arthritis treatment, up to 40% of patients fail to respond adequately. This study aimed to identify transcriptome-based biomarkers of adalimumab response in rheumatoid arthritis (RA) to aid timely switching in non-responder patients and provide a better mechanistic understanding of the pathways involved in response/non-response.MethodsThe Affymetrix Human Transcriptome Array 2.0 (HTA) was used to measure the transcriptome in whole blood at pre-treatment and at 3 months in EULAR good- and non-responders to adalimumab therapy. Differential expression of transcripts was analysed at the transcript level using multiple linear regression. Differentially expressed genes were validated in independent samples using OpenArray™ RT-qPCR.ResultsIn total, 813 transcripts were differentially expressed between pre-treatment and 3 months in adalimumab good-responders. No significant differential expression was observed between good- and non-responders at either time-point and no significant changes were observed in non-responders between time-points. OpenArray™ RT-qPCR was performed for 104 differentially expressed transcripts in good-responders, selected based on magnitude of effect or p value or based on prior association with RA or the immune system, validating differential expression for 17 transcripts.ConclusionsAn early transcriptome signature of DAS28 response to adalimumab has been identified and replicated in independent datasets. Whilst treat-to-target approaches encourage early switching in non-responsive patients, registry evidence suggests that this does not always occur. The results herein could guide the development of a blood test to distinguish responders from non-responders at 3 months and support clinical decisions to switch non-responsive patients to an alternative therapy.
Highlights
Despite the success of Tumour necrosis factor (TNF)-inhibitor therapy in rheumatoid arthritis treatment, up to 40% of patients fail to respond adequately
Cohort characteristics Seventy patients receiving adalimumab therapy were included in the initial study
There was no correlation between this principal component and age, gender, Disease modifying anti-rheumatic drugs (DMARDs) use, baseline 28-joint count disease activity score (DAS28), DAS28 components, RNA integrity number (RIN), or RNA extraction batch
Summary
Despite the success of TNF-inhibitor therapy in rheumatoid arthritis treatment, up to 40% of patients fail to respond adequately. TNF-inhibitor (TNFi) therapies have revolutionised the treatment of rheumatoid arthritis (RA) for many patients, reducing synovial inflammation and long-term disability attributed to cartilage and bone destruction [1,2,3]. Despite their success, up to 40% of patients fail to respond adequately leaving them vulnerable to further disease progression and potential adverse effects of treatment [4, 5]. A reliable biological biomarker or panel of biomarkers would be measured in newly diagnosed patients and throughout the treatment time-course to predict and monitor response to therapy. This would aid timely therapeutic switching in patients in whom the treatment is unlikely to be effective but requires the identification of reliable biomarkers and development of a statistical classifier of treatment response
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
