RESEARCH - Rapid and sustained improvement in bone and cartilage turnover with tocilizumab

[Guest guest]

Arthritis Rheum. 2009 Dec 28;62(1):33-43. [Epub ahead of print]

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.

Garnero P, E, Woodworth T, Smolen JS.

INSERM Unit 664, Lyon, France.

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.

PMID: 20039425

http://www.ncbi.nlm.nih.gov/pubmed/20039425

Not an MD