Expression levels of selected genes can predict individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment

Abstract

Objectives: Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit’s prediction accuracy of individual RA patients’ response to tumor necrosis alpha (TNFα) blockers.

Methods: A retrospective analysis was performed on RA patients reported in published datasets. A prospective analysis assessed RA patients, before and 3 months after starting a TNFα blocker. Clinical response was evaluated according to EULAR response criteria. Blood samples were obtained before starting treatment and were analyzed utilizing the kit which measures expression levels of selected genes by quantitative real time polymerase chain reaction (PCR). ROC analysis was applied to the published datasets and the prospective data.

Results: The Genefron kit analysis of retrospective data predicted the response to a TNFα blocker in 53 of 61 RA patients (86.8% accuracy). In the prospective analysis, the kit predicted the response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response, and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC analysis applied to the two published datasets yielded an AUC of 0.89. ROC analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity – 100%, specificity – 75%) The statistical power obtained in the prospective study was .9.

Conclusion: The diagnostic kit predicted the response to TNFα blockers in a high percentage of patients assessed retrospectively or prospectively. This personal kit may guide selection of a suitable biological drug for the individual RA patient.

Keywords:

• Rheumatoid arthritis
• personal gene expression
• prediction of response

Transparency

Declaration of funding

The Department of Rheumatology at the Tel-Aviv Medical Center has received financial support from Genefron Ltd. in the form of a grant in order to carry out this study.

Author contributions: D.P. was a major contributor to the study design, collected and analyzed the patient data including disease activity, response to therapy, and demographic and clinical characteristics, and was a major contributor in writing the manuscript. Y.S. was a major contributor to the study design, analyzed published datasets, designed the gene expression studies, analyzed and interpreted the gene expression data and was a major contributor to writing the manuscript. Sh.P. was a major contributor to the study design, collected and analyzed the gene expression data and was a major contributor in writing the manuscript. U.A., D.L., I.K., J.W., V.F., A.D., Of.E. and D.C. contributed patient data. Sa.P. collected and collated the patient data. Or.E. was a major contributor to the study design, collected and analyzed the patient data including disease activity, response to therapy, and demographic and clinical characteristics, and was a major contributor in writing the manuscript.

Declaration of financial/other relationships

Sh.P. has disclosed that he is an employee at Genefron Ltd. Y.S. has disclosed that he is a bioinformatics consultant at Genefron Ltd., Jerusalem, Israel.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

None.