Dataset Information

A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures.

ABSTRACT:

Objectives

Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs.

Methods

Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm and biological plausibility of identified proteins was assessed by enrichment analysis.

Results

A total of 180 patients with RA were included in the discovery dataset and 58 in the validation dataset from a UK-based prospective multicentre study. Ten individual proteins were found to be significantly associated with RA clinical outcome measures. The association of T-complex protein 1 subunit η with DAS28 remission was replicated in an independent cohort. Subnetwork analysis of the 10 proteins from the regression analysis identified the ontological theme, with the strongest associations being with acute phase and acute inflammatory responses.

Conclusion

This longitudinal study of 180 patients with RA commencing etanercept has identified several putative protein biomarkers of treatment response to this drug, one of which was replicated in an independent cohort.

SUBMITTER: Ling SF

PROVIDER: S-EPMC10986807 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Publications

A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures.

Ling Stephanie F SF Yap Chuan Fu CF Nair Nisha N Bluett James J Morgan Ann W AW Isaacs John D JD Wilson Anthony G AG Hyrich Kimme L KL Barton Anne A Plant Darren D

Rheumatology (Oxford, England) 20240401 4

<h4>Objectives</h4>Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs.<h4>Methods</h4>Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with t ...[more]

PMID: 37389432

Similar Datasets

Project description:ObjectiveTo evaluate radiographic and clinical outcomes up to 24 months in patients with RA enrolled in the Canadian Methotrexate and Etanercept Outcome study.MethodsIn this open-label non-inferiority trial, patients with inadequate response to MTX received etanercept plus MTX for 6 months and then were randomized to either etanercept monotherapy or continued etanercept plus MTX until 24 months. Radiographic data were analysed using the modified total Sharp score (mTSS), joint space narrowing and erosion scores. Secondary outcomes included the 28-joint DAS with ESR (DAS28-ESR), Simplified Disease Activity Index, Clinical Disease Activity Index, HAQ Disability Index (HAQ-DI) and safety.ResultsTwo hundred five of 258 patients enrolled were randomized (98 etanercept, 107 etanercept plus MTX). At month 24, the mean increase from baseline to month 24 for the etanercept and etanercept plus MTX arms, respectively, for the mTSS were 0.4 (s.d. 1.9) and 0.0 (s.d. 1.4); for joint space narrowing, 0.1 (s.d. 0.6) and 0.0 (s.d. 0.7) and for erosion, 0.3 (s.d. 1.5) and 0.0 (s.d. 1.0). At month 24, the mean increase from month 6 mean scores/count increases for DAS28-ESR were 0.56 (s.d. 1.26) and 0.08 (s.d. 1.50); for Simplified Disease Activity Index, 4.7 (s.d. 13.1) and 0.9 (s.d. 12.5); for Clinical Disease Activity Index, 4.1 (s.d. 12.3) and 1.0 (s.d. 12.3) and for HAQ-DI, 0.20 (s.d. 0.45) and 0.02 (s.d. 0.54). Patients with DAS28-ESR low disease activity (LDA)/remission at month 6 had numerically better outcomes at month 24 than patients with moderate to high disease activity at month 6. In patients with LDA/remission at month 6, outcomes were similar at month 24 between etanercept monotherapy and etanercept plus MTX, whereas patients with moderate to high disease activity at month 6 had numerically better outcomes with etanercept plus MTX than etanercept at month 24. There were no new safety signals and serious adverse events were not different between groups.ConclusionThese results support the possibility of discontinuing MTX in patients who have tolerability issues with MTX if they achieve LDA/remission.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov/; NCT00654368).

Dataset Information

A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures.

Objectives

Methods

Results

Conclusion

Publications

A proteomics study of rheumatoid arthritis patients on etanercept identifies putative biomarkers associated with clinical outcome measures.

Similar Datasets

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