Circulating immune cell biomarkers in Psoriatic Arthritis: associations with clinical manifestations and treatment response in the TOFA-PREDICT trial
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F T Perton1, J N Pouw2, J Spierings2
1Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. f.perton@umcutrecht.nl.
Background:
To investigate the associations of circulating immune cell biomarkers with clinical manifestations and treatment response in Psoriatic Arthritis (PsA), and to evaluate whether these biomarkers improve prediction of individual response to tofacitinib, methotrexate, or etanercept.
Methods:
Data from the TOFA-PREDICT development cohort (n = 80) were used. DMARD naïve patients were randomized to tofacitinib or methotrexate, and csDMARD inadequate responders were randomized to tofacitinib or etanercept. Treatment response (achievement of Minimal Disease Activity) was scored at week 16. Clinical data and peripheral blood mononuclear cells were analyzed at baseline and week 16. Relevant biomarkers for clinical manifestations or treatment response were selected using sparse partial least squares (sPLS) regression and extreme gradient boosting. Associations with PsA clinical manifestations were analyzed using multivariate linear regression. Biomarker profiles for treatment response were derived by sPLS regression. Lastly, a Ridge regression model was used to evaluate whether selected biomarkers improved the prediction of individual treatment response beyond a previously developed clinical model.
Results:
The biomarkers explained up to 27% and 11% of observed variance for psoriasis severity and the swollen joint count, respectively. Baseline biomarker profiles classified etanercept and methotrexate responders relatively well, but did not distinguish tofacitinib responders. Adding biomarker data to clinical data did not improve the accuracy of individual response prediction (AUC-ROC 0.74).
Conclusion:
Our comprehensive set of circulating immune cell biomarkers showed no additional value in precision medicine, when added to clinical predictors. However, the observed associations provide relevant insights into pathophysiological mechanisms underlying differential treatment response and clinical manifestations.
Trial Registration:
EudraCT Trial registration number 2017-003900-28, registration date January 25th 2018.
