Serum cytokine levels towards precision medicine in Still's disease: a subanalysis of a randomized controlled trial of tocilizumab.

OBJECTIVES

To predict the efficacy of IL-6 inhibition in patients with Still's disease by analysing inflammatory cytokine profiles before and during an IL-6 receptor inhibitor therapy.

METHODS

This is a subanalysis of the 52-week, randomized, double-blind, placebo-controlled trial of tocilizumab, an IL-6 receptor inhibitor, in patients with Still's disease. Multiple serum cytokine levels were measured regularly, and their pattern and profiles were analysed based on the response to tocilizumab.

RESULTS

A total of 26 patients (13 in the tocilizumab group and 13 in the placebo group) were enrolled. Before tocilizumab treatment, IL-6 levels were correlated with DAS with 28 joints (r = 0.67, P < 0.01), and IL-1β, IL-6 and IL-18 levels tended to be correlated with systemic feature score (r = 0.33, P = 0.09; r = 0.38, P = 0.05; r = 0.40, P = 0.04, respectively). IL-6 and IL-6 receptor levels were significantly elevated after tocilizumab initiation, while the other cytokines showed no significant difference compared with placebo. Baseline levels of IFN-γ and IL-1β were significantly higher in non-responders compared with responders (28.49 vs 5.65 pg/ml, P = 0.03; 0.26 vs 0.04 pg/ml, P = 0.048), and IFN-γ and IL-18 levels at week 52 remained high in non-responders (15.56 vs 7.03 pg/ml, P = 0.02; 5924 vs 392 pg/ml, P = 0.02).

CONCLUSIONS

The effect of tocilizumab is limited to the IL-6 signalling pathway in Still's disease. Patients who did not respond to tocilizumab exhibited distinct cytokine profiles that pivot the IFN-γ axis. These findings highlight the role of IL-6 inhibition in Still's disease and shed light on its personalized treatment strategies.

CLINICAL TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry; UMIN000012987.