PMID- 20039425
OWN - NLM
STAT- MEDLINE
DCOM- 20100311
LR  - 20220330
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 62
IP  - 1
DP  - 2010 Jan
TI  - Rapid and sustained improvement in bone and cartilage turnover markers with the 
      anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid 
      arthritis patients with an inadequate response to methotrexate: results from a 
      substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab 
      in inadequate responders to methotrexate alone.
PG  - 33-43
LID - 10.1002/art.25053 [doi]
AB  - OBJECTIVE: To investigate the effects of tocilizumab (TCZ) added to a stable 
      dosage of methotrexate (MTX) on biochemical markers of bone and cartilage 
      metabolism in patients in the multicenter double-blind, placebo-controlled OPTION 
      (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders) study who have 
      moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to MTX. 
      METHODS: Included in this study were 416 of the 623 patients with active RA 
      enrolled in the OPTION study. Patients were randomized to receive TCZ (4 mg/kg or 
      8 mg/kg) or placebo intravenously every 4 weeks, with MTX continued at the stable 
      prestudy doses (10-25 mg for 20 weeks, with a final followup at week 24). Serum 
      biochemical markers of bone formation (osteocalcin, N-terminal propeptide of type 
      I collagen [PINP]), bone resorption (C-terminal crosslinking telopeptide of type 
      I collagen [CTX-I] and C-terminal crosslinking telopeptide of type I collagen 
      generated by matrix metalloproteinases [ICTP]), cartilage metabolism (N-terminal 
      propeptide of type IIA collagen [PIIANP]), collagen helical peptide [HELIX-II]), 
      and matrix metalloproteinase 3 (MMP-3) were measured at baseline and at weeks 4, 
      16, and 24. RESULTS: TCZ induced marked dose-dependent reductions in PIIANP, 
      HELIX-II, and MMP-3 levels at week 4 that were maintained until week 24, an 
      effect associated with increased levels of bone formation markers that were 
      significant as compared with placebo only for PINP and only at 4 weeks (P < 0.01 
      for both TCZ doses). TCZ induced significant decreases in the bone degradation 
      markers CTX-I and ICTP, providing initial evidence of a beneficial effect on bone 
      turnover. TCZ-treated patients who met the American College of Rheumatology 50% 
      improvement criteria (achieved an ACR50 response) or achieved clinical remission 
      (as determined by a Disease Activity Score in 28 joints <2.6) at week 24 had 
      greater reductions in ICTP, HELIX-II, and MMP-3 levels as compared with ACR50 
      nonresponders. CONCLUSION: TCZ combined with MTX reduces systemic bone 
      resorption, cartilage turnover, and proteolytic enzyme MMP-3 levels, which 
      provides evidence of a limitation of joint damage and possible beneficial effects 
      on skeletal structure in patients with established moderate-to-severe RA.
FAU - Garnero, Patrick
AU  - Garnero P
AD  - INSERM Unit 664, Lyon, France. patrickgarnero@free.fr
FAU - Thompson, Elizabeth
AU  - Thompson E
FAU - Woodworth, Thasia
AU  - Woodworth T
FAU - Smolen, Josef S
AU  - Smolen JS
LA  - eng
SI  - ClinicalTrials.gov/NCT00106548
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type II)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Procollagen)
RN  - 0 (collagen type I trimeric cross-linked peptide)
RN  - 0 (procollagen Type I N-terminal peptide)
RN  - 0 (procollagen type IIA amino-terminal peptide)
RN  - 104982-03-8 (Osteocalcin)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - I031V2H011 (tocilizumab)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Arthritis, Rheumatoid/blood/*drug therapy
MH  - Biomarkers/blood
MH  - Cartilage, Articular/drug effects/physiology
MH  - Chondrogenesis/*drug effects/physiology
MH  - Collagen Type I
MH  - Collagen Type II/blood
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Drug Tolerance
MH  - Female
MH  - Health Status
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 3/blood
MH  - Methotrexate/*therapeutic use
MH  - Middle Aged
MH  - Osteocalcin/blood
MH  - Osteogenesis/*drug effects/physiology
MH  - Peptide Fragments/blood
MH  - Peptides
MH  - Procollagen/blood
EDAT- 2009/12/30 06:00
MHDA- 2010/03/12 06:00
CRDT- 2009/12/30 06:00
PHST- 2009/12/30 06:00 [entrez]
PHST- 2009/12/30 06:00 [pubmed]
PHST- 2010/03/12 06:00 [medline]
AID - 10.1002/art.25053 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2010 Jan;62(1):33-43. doi: 10.1002/art.25053.