Modular Analysis of Peripheral Blood Gene Expression in Rheumatoid Arthritis Captures Reproducible Gene Expression Changes in Tumor Necrosis Factor Responders

Objective To establish whether the analysis of whole‐blood gene expression is useful in predicting or monitoring response to anti–tumor necrosis factor (anti‐TNF) therapy in patients with rheumatoid arthritis (RA). Methods Whole‐blood RNA (using a PAXgene system to stabilize whole‐blood RNA in the c...

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Published in:Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2015-02, Vol.67 (2), p.344-351
Main Authors: Oswald, Michaela, Curran, Mark E., Lamberth, Sarah L., Townsend, Robert M., Hamilton, Jennifer D., Chernoff, David N., Carulli, John, Townsend, Michael J., Weinblatt, Michael E., Kern, Marlena, Pond, Cassandra M., Lee, Annette, Gregersen, Peter K.
Format: Article
Language:English
Subjects:
Adalimumab
Adult
Aged
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized - pharmacology
Antibodies, Monoclonal, Humanized - therapeutic use
Antirheumatic Agents - pharmacology
Antirheumatic Agents - therapeutic use
Arthritis, Rheumatoid - blood
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - genetics
Cohort Studies
Dose-Response Relationship, Drug
Drug therapy
Etanercept
Female
Gene expression
Gene Expression Regulation - drug effects
Gene Expression Regulation - genetics
Humans
Immunoglobulin G - pharmacology
Immunoglobulin G - therapeutic use
Infliximab
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
Receptors, Tumor Necrosis Factor - therapeutic use
Rheumatoid arthritis
RNA - blood
RNA - genetics
TNF inhibitors
Treatment Outcome
Tumor Necrosis Factor-alpha - antagonists & inhibitors
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Summary:Objective To establish whether the analysis of whole‐blood gene expression is useful in predicting or monitoring response to anti–tumor necrosis factor (anti‐TNF) therapy in patients with rheumatoid arthritis (RA). Methods Whole‐blood RNA (using a PAXgene system to stabilize whole‐blood RNA in the collection tube) was obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a combined total of 240 RA patients who were beginning therapy with anti‐TNF. We used an approach to gene expression analysis that is based on modular patterns of gene expression, or modules. Results Good and moderate responders according to the European League Against Rheumatism criteria exhibited highly significant and consistent changes in multiple gene expression modules after 14 weeks of therapy, as demonstrated by hypergeometric analysis. Strikingly, nonresponders exhibited very little change in any modules, despite exposure to TNF blockade. These patterns of change were highly consistent across all 3 cohorts, indicating that immunologic changes after TNF treatment are specific to the combination of both drug exposure and responder status. In contrast, modular patterns of gene expression did not exhibit consistent differences between responders and nonresponders at baseline in the 3 study cohorts. Conclusion These data provide evidence that using gene expression modules related to inflammatory disease may provide a valuable method for objective monitoring of the response of RA patients who are treated with TNF inhibitors.
ISSN:2326-5191
2326-5205
DOI:10.1002/art.38947