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Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.

ABSTRACT: Sustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in the peripheral blood of patients with RA. Our data reveal that drug treatments alter the molecular profile closer to that of HCs at the transcriptome, serum proteome, and immunophenotype level. Patient follow-up suggests that the molecular profile after drug treatments is associated with long-term stable CR. In addition, we identify molecular signatures that are resistant to drug treatments. These signatures are associated with RA independently of known disease severity indexes and are largely explained by the imbalance of neutrophils, monocytes, and lymphocytes. This high-dimensional phenotyping provides a quantitative measure of molecular remission and illustrates a multi-omics approach to understanding drug response.

SUBMITTER: Tasaki S

PROVIDER: S-EPMC6048065 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.

Tasaki Shinya S Suzuki Katsuya K Kassai Yoshiaki Y Takeshita Masaru M Murota Atsuko A Kondo Yasushi Y Ando Tatsuya T Nakayama Yusuke Y Okuzono Yuumi Y Takiguchi Maiko M Kurisu Rina R Miyazaki Takahiro T Yoshimoto Keiko K Yasuoka Hidekata H Yamaoka Kunihiro K Morita Rimpei R Yoshimura Akihiko A Toyoshiba Hiroyoshi H Takeuchi Tsutomu T

Nature communications 20180716 1

Sustained clinical remission (CR) without drug treatment has not been achieved in patients with rheumatoid arthritis (RA). This implies a substantial difference between CR and the healthy state, but it has yet to be quantified. We report a longitudinal monitoring of the drug response at multi-omics levels in the peripheral blood of patients with RA. Our data reveal that drug treatments alter the molecular profile closer to that of HCs at the transcriptome, serum proteome, and immunophenotype lev ...[more]

PMID: 30013029

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Project description:BACKGROUND:Reliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission. METHODS:RA patients on >?6?months stable therapy in stable low disease activity (DAS28-ESR ??3.2) were assessed every 3?months for 1?year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as 'low disease activity state' (LDAS). Patients not fulfilling any remission criteria over 1?year were classified as 'persistent disease activity' (PDA). MBDA score was measured at baseline/3/6?months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test. RESULTS:Of 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1?year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68-0.75) and IR/SR (AUROCs 0.65-0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65-0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1?year. CONCLUSIONS:This study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.

Dataset Information

Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.

Publications

Multi-omics monitoring of drug response in rheumatoid arthritis in pursuit of molecular remission.

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