To evaluate dynamics of cytokine profile characteristics in patients with rheumatoid arthritis (RA) treated with tocilizumab and to identify parameters that can be used to predict the effectiveness of therapy.
42 patients (32 women) aged 43-55 (mean 50.5) years with the duration of disease 23-81 (mean 56.5 months), DAS28 6.4 (5.8-7.05). Each patient was given 6 i/v infusions of 8 mg tocilizumab/day at 4 week intervals in addition to standard therapy. Serum levels of IL-1b, IL-1Pa, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF-basic, G-CSF, GM-CSF, IFN-g, IP-10, MCP-1, MIP-1alpha, MIP-1b, PDGF bb, RANTES, TNF-alpha, VEGF were determined by xMAP multiplex technology.
Good therapeutic effect in accordance with EULAR criteria was documented in 35 and satisfactory one in 7 patients; remission based on CDAI occurred in 33% of the cases. The levels of proinflammatory (IL-1b, -2, -6, -12, -15, -17, IFN-gamma, TNF-alpha) and anti-inflammatory (IL-4, -5, -9, -10, -13) cytokines, hemokines (IL-8, MCP-1, MIP-1a, MIP-1b, MIP-1b) and growth factors (IL-7, GM-CSF, VEGF, FGF basic, IP-10) dropped down by week 24 of the treatment (p < 0.05). Remission based on CDAI was associated with higher baseline levels of IL-1b, -2, GM-CSF and TNF-alpha and good outcome according to EULAR criteria with the rapid fall in IL-10 and -13 levels.
Therapy with tocilizumab results in the rapid and well apparent decrease in the concentration of the practically entire spectrum of cytokines. Measurement of IL-1b, -2, -10, -13, GM-CSF and TNF-alpha may be useful for the prediction of the effectiveness of therapy of RA with tocilizumab.