In Ah CHOI1, Sang Jin LEE2, Won PARK3, Sung Hwan PARK4, Seung-cheol SHIM5, Han Joo BAEK6, Dae-Hyun YOO7, Hyun Ah KIM8, Soo Kon LEE9, Yun Jong LEE10, Young Eun PARK11, Hoon-Suk CHA12, Eun Young LEE13, Eun Bong LEE13, Yeong Wook SONG2

1Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea
2Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Institute, Seoul National University, Seoul, South Korea
3Department of Internal Medicine, Inha University Hospital, Incheon, South Korea
4Department of Internal Medicine, The Catholic University of Korea Seoul St. Mary’s Hospital, Seoul, South Korea
5Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea
6Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea
7Department of Internal Medicine, Hanyang University Medical Center, Seoul, South Korea
8Department of Internal Medicine, Hallym University Medical Center, Anyang, South Korea
9Department of Internal Medicine, CHA Bundang Medical Center, Seongnam, South Korea
10Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
11Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea
12Department of Internal Medicine, Sam Sung Medical Center, Seoul, Seoul, South Korea
13Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

Keywords: Arthritis, interleukin-6, interleukin-33, rheumatoid, tocilizumab


Objectives: This study aims to examine the effects of tocilizumab therapy on serum levels of interleukin (IL)-33 and IL-6 in rheumatoid arthritis (RA) patients.
Patients and methods: Interleukin-33 and IL-6 levels in serum samples from 83 RA patients (10 males, 73 females; mean age 51.9 years; range, 26 to 77 years) and 12 healthy controls (2 males, 10 females; mean age 52.2 years; range, 39 to 62 years) were compared by cross-sectional, case control analysis. Of the RA patients, 40 received 24 weeks of tocilizumab therapy and were assigned to the prospective cohort. These 40 patients were then divided into two subgroups as responders and non-responders according to the American College of Rheumatology (ACR) 20. The remaining 43 RA patients did not receive tocilizumab therapy. Serum cytokine levels were analyzed at baseline and after 24 weeks of tocilizumab therapy in these patients.
Results: Interleukin-33 and IL-6 concentrations were significantly higher in RA patients than in healthy controls (p<0.001 for both). Serum IL-33 levels in RA patients showed a significant correlation with rheumatoid factor titer (r=0.660, p<0.001), and IL-6 levels showed a significant correlation with high-sensitivity C-reactive protein levels (Spearman's rank correlation coefficient=0.482, p<0.001). Serum IL-33 levels decreased significantly after 24 weeks of tocilizumab therapy (p<0.001); this was particularly marked in ACR20 responders (p<0.001). However, the decrease in non-responders was not significant (p=0.066). Changes in serum IL-6 levels after 24 weeks of tocilizumab therapy were not significant in either ACR20 responders or non-responders.
Conclusion: Serum IL-33 levels in RA patients receiving tocilizumab therapy decreased significantly, particularly in ACR20 responders. Thus, IL-33 may be a useful marker for monitoring responses to tocilizumab therapy.

Citation: Choi IA, Lee SJ, Park W, Park SH, Shim SC, Baek HJ. Effects of tocilizumab therapy on serum interleukin-33 and interleukin-6 levels in patients with rheumatoid arthritis. Arch Rheumatol 2018;33(4):389-394.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This research was supported by grants from the Ministry of Science, ICT and Future Planning, Republic of Korea (NRF-2015M3A9B6052011) and the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI14C1277), and partly by a grant from JW Pharmaceuticals.