Ex vivo inhibited cytokine profiling may explain inferior treatment response to golimumab after adalimumab failure in rheumatoid arthritis

OBJECTIVES: Clinical data suggest that the response of rheumatoid arthritis patients to treatment with golimumab is much lower among those who switched from adalimumab than among those who switched from etanercept. To elucidate the mechanism behind this difference in response to sequential biologic treatment, we examined the effect of TNF inhibitors on ex vivo cytokine production profiling. METHODS: In a prospective cohort study, blood samples were obtained from patients before the start of a biologic. Peripheral blood mononuclear cells were pre-incubated for 1 hour with the therapeutic in vivo concentration of adalimumab, etanercept or golimumab and stimulated for 24 hours with heat killed Candida albicans or Pam3Cys. Cytokine concentrations of IL-1beta, IL-6 and TNFalpha were determined by ELISA. RESULTS: Ex vivo cytokine profiling was performed in 71 patients. Golimumab, adalimumab and etanercept significantly (p<0.01) decreased Candida albicans-induced IL-1beta and IL-6 production and Pam3Cys-induced IL-6 production. In contrast to etanercept, golimumab and adalimumab decreased the concentration of TNFalpha below the detection limit. Absolute changes in cytokine levels after inhibition by golimumab or adalimumab were all significantly correlated (Spearman rank rs: 0.52-0.99, p