Anti-cyclic citrullinated peptide antibody titers decrease in rheumatoid arthritis patients treated with tocilizumab: A pilot study

Abstract

Objectives: To analyze the effects of tocilizumab on peripheral B-cell subpopulation and its ability to produce anti-cyclic citrullinated peptide (CCP) antibody in patients with rheumatoid arthritis (RA).

Methods: Thirteen consecutive RA patients initiated with tocilizumab were enrolled in our prospective study. Anti-CCP antibody titers and clinical parameters were evaluated during treatment. Peripheral blood B-cell subsets were analyzed using flow cytometry according to the Human Immunology Project.

Results: Disease activity was significantly improved and anti-CCP antibody titers significantly decreased at week 24 compared to baseline. The percentages of post-switch memory B cells in CD19+ cells transiently increased at week 12, but there was no significant difference in any of the investigated B-cell subpopulations at week 24 compared to baseline. The ratios of post-switch memory to naïve B cells (post-switch/naïve) correlated negatively with anti-CCP antibody titers regardless of the time-points.

Conclusion: Our study indicated that tocilizumab has a potential to reduce anti-CCP antibody production presumably by affecting post-switch/naïve ratio, and that anti-CCP antibody titers reflect B-cell distribution/subpopulation. As anti-CCP antibodies are produced in lymph nodes or ectopic lymphoid structures in synovial tissues, not in circulation, transient increment of post-switch memory B cells after tocilizumab treatment may reflect the altered balance of B-cell distribution between circulation and arthritic joints, resulting in suppressed production of anti-CCP antibody in situ.

Keywords:

• Anti-cyclic citrullinated peptide antibody
• B-cell subpopulation
• rheumatoid arthritis
• tocilizumab

Acknowledgements

We thank M. Shitamichi for her technical contributions.

Conflict of interest

T.A. received grants and personal fees from Astellas, grants and personal fees from Takeda, grants and personal fees from Mitsubishi Tanabe, grants and personal fees from Chugai, grants and personal fees from Pfizer, grants and personal fees from Daiichi Sankyo, grants from Otsuka, personal fees from Eisai, personal fees from AbbVie, outside the submitted work. S.Y. received grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Bristol Myers Squibb, personal fees from Tanabe-Mitsubishi Pharmaceutical, grants from Novartis Pharmaceutical, personal fees from Pfizer, outside the submitted work. The other authors have declared no conflict of interest associated with this manuscript. Y.M. and M.S. are employees of Chugai Pharmaceutical.