Correlations between changes in cytokines and clinical outcomes for early phase (proof of concept) trials in active diffuse systemic sclerosis using data from an imatinib study

OBJECTIVE Data from a small study testing imatinib to treat SSc were used to determine if cytokine changes were related to differences in clinical parameters to model future early phase trials pairing cytokine changes and clinical parameters. METHODS Plasma and punch skin biopsy specimens collected at baseline and 6 months were analysed for levels of 26 fibrotic and inflammatory cytokines using multiplexed immunoassays and ELISA. Seven of nine patients on active treatment had paired data. Biopsies were biopulverized and standardized to protein levels in the tissue homogenate. Plasma was frozen at -80°C and analysed using multiplexed immunoassays or ELISAs standardized to CRP. Correlations between fold changes in cytokines and differences in clinical parameters (skin score, physician and patient global assessments and HAQ) were performed. P < 0.01 was considered significant. RESULTS After 6 months of imatinib treatment, plasma levels of soluble vascular cell adhesion molecule 1 decreased significantly (P < 0.001), while tissue levels of soluble intercellular adhesion molecule 1 increased (P < 0.01). Some significant correlations between fold changes in certain plasma fibrotic and inflammatory cytokines and changes in clinical parameters after 6 months of treatment were found: patient global scores and IL-13 (r = 0.964, P < 0.0001); ESR and IL-12p70 (r = -0.903, P < 0.01); in tissue samples, patient global score and soluble E-selectin (r = 0.913, P < 0.01); and physician global score with sCD40L (r = -0.883, P < 0.01). CONCLUSION Some serum and tissue cytokines may have a role in early phase clinical trials of SSc, correlating with changes in clinical parameters. Serum and tissue samples could be analysed in early phase trials to determine whether they support the clinical observations. TRIAL REGISTRATION http://clinicaltrials.gov/show/NCT01545427.