PMID- 23925361
OWN - NLM
STAT- MEDLINE
DCOM- 20150505
LR  - 20161125
IS  - 0578-1426 (Print)
IS  - 0578-1426 (Linking)
VI  - 52
IP  - 4
DP  - 2013 Apr
TI  - [The efficacy and safety of tocilizumab combined with disease-modifying 
      anti-rheumatoid drugs in the treatment of active rheumatoid arthritis: a 
      multi-center, randomized, double-blinded, placebo-controlled trial].
PG  - 323-9
AB  - OBJECTIVE: To evaluate the efficacy and safety of human anti-interleukin-6 (IL-6) 
      receptor antibody (tocilizumab) in combination with disease-modifying 
      anti-rheumatoid drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) 
      patients with moderate to severe activity and inadequate response to DMARDs. 
      METHODS: The present study was a multi-center, randomized, double-blinded, 
      placebo controlled trial. Eligible patients were randomized (tocilizumab:Placebo 
      = 2:1) to one of two groups: tocilizumab 8 mg/kg group or placebo group. The drug 
      was administered every 4 weeks by infusion along with stable dose of DMARDs. The 
      primary analysis evaluated at week 24 included: the proportion of patients with 
      American College of Rheumatology (ACR)20, ACR50 and ACR70 response; the average 
      changes of ACR core components from baseline; the proportion of patients with 
      disease activity score (DAS28) </= 3.2 and DAS28 < 2.6. Patients who completed 
      double-blinded phase could choose to enter 24-week open-label therapy with 
      tocilizumab 8 mg/kg infusion every 4 weeks. RESULTS: Totally 139 patients from 
      tocilizumab group and 69 patients from placebo group completed the 24-week 
      double-blinded period respectively with comparable baseline characteristics. The 
      proportion of patients with ACR20, ACR50 and ACR70 in tocilizumab group was 
      significantly higher than that in placebo group: 69.8% vs 24.6% (P < 0.05), 38.8% 
      vs 10.1% (P < 0.05) and 12.9% vs 2.9% (P < 0.05) respectively. ACR core 
      components change, proportion of patients with DAS28 </= 3.2 and DAS28 < 2.6 were 
      all better in tocilizumab group than those in the placebo group. Decreased level 
      of biomarkers C-terminal crosslinking telopeptide of type I collagen generated by 
      matrix metalloproteinases (ICTP), matrix metalloproteinase 3 (MMP-3) and 
      N-terminal propeptide of type IIA collagen (PIIANP) were observed in patients 
      with tocilizumab treatment, indicating its positive effects on bone metabolism. A 
      total of 202 patients received tocilizumab treatment in the study with the 
      longest duration as 48 weeks, and all the indexes were improved further with the 
      elongation of the treatment time. During the doubled blind phase, 42.4% of 
      patients in the tocilizumab group had >/= 1 adverse event (AE), compared with 27.9% 
      of patients in the control group. The most common AE was infection, and most of 
      the AEs were mild to moderate. Serious AEs occurred in 0.7% and 5.9% of patients 
      in the tocilizumab and control groups, respectively. More patients in the 
      tocilizumab group had higher percentage of increased alanine transaminase and 
      aspartate transaminase (12.9% and 9.4%) compared to the placebo group (4.4% and 
      4.4%). Increase of total cholesterol, high density lipoprotein, low density 
      lipoprotein, and triacylglycerol were observed in the tocilizumab group, but no 
      increase of occurrence of cardiac events. No additional safety signals were found 
      during the extension phase. CONCLUSION: The study showed that tocilizumab 
      combined with DMARDs was safe and effective in reducing articular and systemic 
      symptoms in patients with an inadequate response to DMARDs.
FAU - Shi, Qun
AU  - Shi Q
AD  - Department of Immunology, Peking Union Medical College Hospital, Peking Union 
      Medical College, Chinese Academy of Medical Sciences, Beijing 100032, China. 
      zhaoyan_pumch 2002@yahoo.com.cn
FAU - Zhao, Yan
AU  - Zhao Y
FAU - Bao, Chun-de
AU  - Bao CD
FAU - Li, Xing-Fu
AU  - Li XF
FAU - Huang, Feng
AU  - Huang F
FAU - Zhu, Ping
AU  - Zhu P
FAU - Li, Zhan-Guo
AU  - Li ZG
FAU - Gu, Jie-Ruo
AU  - Gu JR
FAU - Zhang, Zhi-Yi
AU  - Zhang ZY
FAU - Zhao, Dong-Bao
AU  - Zhao DB
FAU - Zhao, Shuang-Ling
AU  - Zhao SL
FAU - Jiang, Qiu-di
AU  - Jiang QD
FAU - Tian, Jin
AU  - Tian J
FAU - Zhang, Feng-Chun
AU  - Zhang FC
LA  - chi
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - China
TA  - Zhonghua Nei Ke Za Zhi
JT  - Zhonghua nei ke za zhi
JID - 16210490R
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
RN  - I031V2H011 (tocilizumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antirheumatic Agents/adverse effects/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Humans
MH  - Interleukin-6
MH  - Receptors, Interleukin-6
MH  - Safety
MH  - Severity of Illness Index
MH  - Treatment Outcome
EDAT- 2013/08/09 06:00
MHDA- 2015/05/06 06:00
CRDT- 2013/08/09 06:00
PHST- 2013/08/09 06:00 [entrez]
PHST- 2013/08/09 06:00 [pubmed]
PHST- 2015/05/06 06:00 [medline]
PST - ppublish
SO  - Zhonghua Nei Ke Za Zhi. 2013 Apr;52(4):323-9.