IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review

Abstract

Tocilizumab (TCZ) is an interleukin-6 (IL-6) inhibitor used for the treatment of rheumatoid arthritis (RA). It was developed in 2008, and its effectiveness is supported by evidence from all over the world based on its first decade of use. Although the overall efficacy and safety profiles of TCZ are similar to those of tumor necrosis factor (TNF) inhibitors, TCZ displays certain differences. The most notable advantage of TCZ is its usefulness as a monotherapy. Additionally, TCZ is favorable in the improvement of systemic inflammatory symptoms such as anemia and fatigue. The low immunogenicity of TCZ contributes favorably to long-term drug retention. Due to frequent relapse after TCZ cessation, TCZ use should be tapered beyond remission. During TCZ therapy, C-reactive protein (CRP) is unable to recognize disease activity and the severity of infection. The most common adverse events (AEs) are infection and abnormalities in laboratory findings including dyslipidemia, neutropenia, thrombocytopenia, and abnormality of liver enzymes. TCZ obscures the symptoms of infection. Therefore, stealth infections without obvious CRP elevation can sometimes cause severe damage to patients. Lower intestinal perforation is an uncommon but serious AE in TCZ therapy. Further clinical investigations will continue to refine the IL-6 inhibitory strategy.

Keywords:

• Interleukin-6
• rheumatoid arthritis
• tocilizumab
• sarilumab
• sirukmab

Acknowledgement

The authors would like to thank Enago (www.enago.jp) for the English language review.

Conflict of interest

AO received honoraria for speech from Chugai Pharmaceutical Co, Asahi Kasei Pharm Co, Sanofi KK, Janssen Pharmaceutical KK, Pfizer Co, Bristol-Myers Squibb Co, Eisai Co, GlaxoSmithKline KK, Novartis Co, AYUMI Pharmaceutical Co, and consultant fee from Chugai Pharmaceutical Co. YK and SH have no conflicts of interest to disclosure. KY is a patent holder on the applied patent for the clinical use of tocilizumab on Still’s disease. KY also received lecture fee from Chugai Pharmaceutical Co.