Date: Sunday, November 8, 2020
Session Type: Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Interleukin-6 (IL-6) is a key cytokine in the pathogenesis of rheumatoid arthritis (RA). Tocilizumab (TCZ) and Sarilumab (SAR) are monoclonal antibodies that bind to membrane and soluble forms of human IL-6 receptor, efficiently inhibiting IL-6/STAT3 signaling. Our group had previously reported the bioassay for measuring the strength of IL-6/STAT3 signal inhibition by TCZ (Arthritis Research & Therapy 2017.19:231). In this study, we measured phosphorylated STAT3 (pSTAT3) in RA patients treated with subcutaneous (s.c) administration of TCZ and SAR, in order to assess the difference in the strength of IL-6/STAT3 signal inhibition among both medications.
Methods: RA patients who achieved low disease activity (CDAI< =10) by treatment with weekly or biweekly administration of 162 mg s.c of TCZ (TCZ q1w, n = 8, and TCZ q2w group, n = 8), and those with 200 mg s.c of SAR biweekly (SAR q2w group, n = 7) were collected. Whole blood samples from each group were stimulated with each concentration of recombinant human (rh) IL-6 (0, 0.1, 1, 10, 100 ng/ml). The proportion of pSTAT3 positive CD4+ T cells was measured by phosflow cytometric analysis.
Results: The clinical characteristics of each group were not different in each group (Table1). Proportion of pSTAT3 positive CD4+ T cells stimulated by 100ng/ml of rhIL-6 showed significant difference in each group (median 1.8 [0.9-3.0]% vs 7.7 [2.9-8.0]% vs 12.5 [11.4-16.6]% in TCZ q1w, SAR q2w, TCZ q2w group, respectively, p< 0.05 for all comparisons)(Figure 1).
Conclusion: The strength of IL-6/STAT3 signal inhibition by SAR 200mg q2w showed significantly higher level than that of TCZ s.c q2w but lower than TCZ s.c q1w. The result of this study might be useful in considering the adjustment of the strength of IL-6 blockade treatment in each RA patient.
To cite this abstract in AMA style:Saito S, Suzuki K, Yoshimoto K, Kondo Y, Kikuchi J, Otomo K, Hanaoka H, Kaneko Y, Takeuchi T. The Strength of IL-6/STAT3 Signal Inhibition by SAR S.c q2w Showed Significantly Higher Level Than That of TCZ S.c q2w but Lower Than TCZ S.c q1w [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/the-strength-of-il-6-stat3-signal-inhibition-by-sar-s-c-q2w-showed-significantly-higher-level-than-that-of-tcz-s-c-q2w-but-lower-than-tcz-s-c-q1w/. Accessed October 20, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-strength-of-il-6-stat3-signal-inhibition-by-sar-s-c-q2w-showed-significantly-higher-level-than-that-of-tcz-s-c-q2w-but-lower-than-tcz-s-c-q1w/