Differences in the strength of inhibition of interleukin-6 signalling by subcutaneous sarilumab and tocilizumab in rheumatoid arthritis patients.

Abstract

To assess differences in the strength of inhibition of IL-6/STAT3 signalling induced by subcutaneously (sc) administered tocilizumab (TCZ) and sarilumab (SAR). Data were collected on patients with rheumatoid arthritis (RA) who achieved low disease activity (Clinical Disease Activity Index [CDAI]≤10) following treatment with weekly or bi-weekly administration of 162 mg sc of TCZ (TCZ qw group, n=8; TCZ q2w group, n=8), bi-weekly doses of 200 mg sc of SAR (SAR q2w group, n=7), or MTX (n=8) as a control. The clinical characteristics of each group were collected, and the serum concentrations of IL-6 and soluble IL-6 receptor (sIL-6R) were measured using ELISA. Whole blood samples from each group were stimulated with 100 ng/ml of IL-6. The proportion of phosphorylated (p)STAT3-positive CD4+ T cells was measured using phosflow cytometric analysis. The proportion of pSTAT3-positive CD4+ T cells following stimulation with 100 ng/ml of recombinant human IL-6 was significantly different among the groups (median 1.8% [0.9-3.0] vs. 7.7% [2.9-8.0] vs. 12.5% [11.4-16.6] vs. 71.5% [68.0-78.5] for the TCZ qw, SAR q2w, TCZ q2w, and MTX control groups, respectively; p<0.01 for all comparisons). SAR 200 mg q2w showed significantly stronger inhibition of IL-6/STAT3 signalling than TCZ sc q2w but weaker inhibition than TCZ sc qw. The results of this study may be useful for adjusting the IL-6 blockade treatment for patients with RA.