Add-on tocilizumab versus conventional treatment for systemic sclerosis, and cytokine analysis to identify an endotype to tocilizumab therapy

Abstract

Objectives: To evaluate the anti-interleukin (IL)-6 receptor antibody tocilizumab (TCZ) as a treatment of systemic sclerosis (SSc), a randomised parallel group study was conducted, and compared their results and baseline cytokine/chemokine profiles.

Methods: Patients were assigned to a TCZ add-on group (TCZ group, n = 7) and a conventional therapy group (Conv group, n = 6). TCZ (8 mg/kg/month) for 6 months, and the modified Rodnan total skin score (mRSS) were used to compare the efficacy. The association of medical history, baseline pulmonary function tests, blood cell counts, serum C-reactive protein (CRP) and 26 cytokines/chemokines and decrease in mRSS were analysed.

Results: The mean change in mRSS was larger in the TCZ group (6.3) than in the Conv group (3.4), but the difference was not statistically significant because of high variance in the TCZ group. Patients with shorter disease histories and higher CRP had larger decreases in mRSS, and the decrease in mRSS was negatively correlated with IL-13 and C–C motif chemokine ligand (CCL)5.

Conclusion: Although significant between-group differences were not observed, some patients had a decrease in mRSS. Short disease duration, high CRP, low IL-13 and low CCL5 may represent an SSc endotype responsive to TCZ therapy.

Keywords:

• Systemic sclerosis
• tocilizumab
• IL-6
• IL-13
• CCL5

Acknowledgements

We are very grateful to Professor Toshio Tanaka and Professor Atushi Kumanogoh for their support and insightful comments. We thank Dr Hiroyuki Murota for his important comments on the clinical evaluation. We also thank Mrs. Hiromi Nishinaka for her outstanding assistance.

Conflict of interest

Y.S. has received speaker fees from Chugai Pharmaceutical Co. Ltd. and consulting fees from F. Hoffmann-La Roche, Ltd. The TCZ used in this study was supplied by Chugai Pharmaceutical Co. Ltd. All other authors have declared no conflicts of interest.

Additional information

Funding

This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (#14591444).