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

1, 2, 3, 4, 5, 6, 7, 8

 

  1. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. shsaito@keio.jp
  2. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  3. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  4. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  5. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  6. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  7. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
  8. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

CER16094
2023 Vol.41, N°7
PI 1451, PF 1455
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PMID: 36533996 [PubMed]

Received: 28/07/2022
Accepted : 17/10/2022
In Press: 15/12/2022
Published: 10/07/2023

Abstract

OBJECTIVES:
To assess differences in the strength of inhibition of IL-6/STAT3 signalling induced by subcutaneously (sc) administered tocilizumab (TCZ) and sarilumab (SAR).
METHODS:
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.
RESULTS:
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).
CONCLUSIONS:
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.

DOI: https://doi.org/10.55563/clinexprheumatol/k0ctlf

Rheumatology Article