Abstract
Accumulating clinical evidence show that not all rheumatoid arthritis (RA) patients benefit to the same extent from a Tripterygium wilfordii Hook F (TwHF)-based therapy-Tripterysium glycosides tablets (TG tablets), which emphasizes the need of predictive biomarkers and tools for drug response. Herein, we integrated TG tablets' response-related miRNA and mRNA expression profiles obtained from the clinical cohort-based microarray, miRNA target prediction, miRNA-target gene coexpression, as well as gene-gene interactions, to identify four candidate circulating miRNA biomarkers that were predictive of response to TG tablets. Moreover, we applied the support vector machines (SVM) algorithm to construct the prediction model for the treatment outcome of TG tablets based on the levels of the candidate miRNA biomarkers, and also confirmed its good performance via both 5-fold cross-validation and the independent clinical cohort validations. Collectively, this circulating miRNA-based biomarker model may assist in screening the responsive RA patients to TG tablets and thus potentially benefit individualized therapy of RA in a daily clinical setting.
Highlights
Rheumatoid arthritis (RA) represents a systemic autoimmune disorder that is characterized by chronic arthritis, synovium hyperplasia, bone and cartilage erosion, as well as joint swelling and destruction
Responders to TG tablets were defined as patients who were treated with TG tablets for 12 weeks achieved American College of Rheumatology Criterion of 20% (ACR 20), and non-responders were defined as patients who were treated with TG tablets for 12 weeks but not achieved ACR 20 (American College of Rheumatology Subcommittee on Rheumatoid Arthritis, 2002)
An increasing number of clinical evidence show that not all RA patients benefit to the same extent from the Tripterygium wilfordii Hook F (TwHF)-based therapy, suggesting that it is of great significance to develop predictive biomarkers and tools for determination of patients who may have a low probability of response to the TwHF-based therapy, so as to allow clinicians to choose alternative drugs at an earlier stage of the disease without any delay of efficacious treatment, in line with the concept of precision medicine (Bluett and Barton, 2017)
Summary
Rheumatoid arthritis (RA) represents a systemic autoimmune disorder that is characterized by chronic arthritis, synovium hyperplasia, bone and cartilage erosion, as well as joint swelling and destruction. TwHF-based therapy has been extensively used in the treatment of RA as a disease-modifying anti-rheumatic drug (DMARD) for many years in China (Bao and Dai, 2011; Wang et al, 2016). Prediction of Response to TwHF-Based Therapy randomized controlled trials (Chang et al, 1999; Lv et al, 2015; Wang et al, 2016, 2017). Wang et al (2016) reported that TG tablets alone attained a markedly higher modified American College of Rheumatology Criterion of 20% (ACR 20) response, compared with methotrexate, leflunomide, sulphasalazine, tacrolimus, minocycline; Lv et al (2015) observed that the combination of methotrexate and TG tablets was better than methotrexate monotherapy in controlling disease activity in patients with active RA. About 30% of RA patients treated with TG tablets fail to achieve clinical improvement, which emphasizes the need of predictive biomarkers and tools
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