Objective To summarize the efficacy and safety profile of Tocilizumab (TCZ), a humanized monoclonal antibody against interleukin-6 (IL-6), approved for the treatment of rheumatoid arthritis (RA). Methods A systematic literature review was conducted to identify English language articles within Pubmed and the Cochrane Library from January 1989 to August 2011 reporting results from phase III TCZ double-blinded randomized controlled trials (RCT), non-controlled clinical trials and open-label extensions with duration ≥ 6 months. Study outcomes had to include at least one of the following: American College of Rheumatology (ACR) 20, 50, 70; tender/swollen joint count, HAQ disability, radiographic outcomes and drug persistence. Phase II RCTs were included only if they contained relevant information not available in phase III RCTs. To review TCZ pharmacology, relevant studies were selected to evaluate pharmacokinetics and pharmacodynamics. Results Ten published clinical trials (7 phase 3, 3 phase 2) for TCZ were retrieved (7,833 articles initially identified) and 31 from Cochrane library. Compared to MTX monotherapy, TCZ 8 mg/Kg monotherapy had higher rates of ACR20 (p<0.001), ACR50 (p=0.002) and ACR70 (p<0.001) scores at week 24. TCZ 8mg/Kg IV + oral MTX had a higher ACR20 response rate than placebo + oral MTX in patients with RA that failed to respond to MTX or anti-TNF therapy (p<0.001). Patients on TCZ 8mg/Kg had less radiographic progression on Sharp-Genant Score, (85% had no progression) than the control group (67% had no progression, p<0.001). The rate of serious infections was 4.7 events /100 patient years of exposure in the TCZ groups. A greater frequency of neutropenia, thrombocytropenia, hyperlipidemia, and transaminitis was observed with TCZ compared to placebo. Conclusion The short term efficacy and safety profile of TCZ is promising. Additional long term safety data are needed to better characterize the risk-benefit profile of this agent.
【저자키워드】 Tocilizumab, IL-6, rheumatoid arthritis, juvenile idiopathic arthritis, MRA,