RESEARCH - Long-term effects of Remicade on bone and cartilage turnover markers in patients with RA

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ls of the Rheumatic Diseases 2008;67:353-357

Copyright © 2008 BMJ Publishing Group Ltd & European League Against

Rheumatism

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EXTENDED REPORTS

Long-term effects of infliximab on bone and cartilage turnover markers

in patients with rheumatoid arthritis

F Chopin 1, P Garnero 2, A le Henanff 3, F Debiais 4, A Daragon 5, C

Roux 6, J Sany 7, D Wendling 8, C Zarnitsky 9, P Ravaud 3, T 1

1 Inserm Unit 890, University Hospital of St-Etienne, France

2 Inserm Unit 664 and Molecular Markers, Synarc, Lyon, France

3 Hôpital Bichat, Paris, France

4 University Hospital of Poitiers, France

5 University Hospital of Rouen, France

6 Hôpital Cochin, Paris, France

7 Hôpital Lapeyronie, Montpellier, France

8 University Hospital of Besançon, France

9 Groupe Hospitalier du Havre, France

Background: Rheumatoid arthritis (RA) is associated with systemic bone

loss, subchondral bone erosion and cartilage degradation under the

control of pro-inflammatory cytokines, including tumour necrosis

factor (TNF). Therefore, we tested the hypothesis that administration

of infliximab, an anti-TNF drug in the treatment of RA, would modulate

systemic and local bone resorption and reduce cartilage degradation.

Methods: We performed a prospective study of a multicentric cohort of

48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4

(7.8) years, who started infliximab after failure of other

disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54

weeks after initiating Infliximab therapy we measured the following

biochemical markers: pro-collagen serum type I N-terminal propeptide

(PINP), a marker of bone formation; serum C-terminal cross-linked

telopeptide of type I collagen (CTX-I), a marker of cathepsin

K-mediated bone collagen degradation believed to reflect systemic bone

resorption; serum C-terminal cross-linked telopeptide of type I

collagen (ICTP), an index of matrix metalloprotease (MMP) mediated

type I collagen degradation reflecting preferential joint metabolism;

and urinary CTX-II a biochemical markers of cartilage degradation.

Total hip and lumbar spine bone mineral density (BMD) was assessed at

baseline, and after 6 and 12 months by dual-energy x-ray

absorptiometry (DXA). No patient received bisphosphonates while 77%

were under oral glucocorticoids.

Results: BMD remained stable over 1 year. Serum CTX-I levels rapidly

decreased by 19% and 28% at week 6 and week 22, respectively (analysis

of variance (ANOVA) p = 0.032) values returning to pre-treatment level

at week 54. By contrast, ICTP levels progressively declined with a

maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP

levels remained stable over time, which led to a 30 to 40% improvement

in bone remodelling balance, as assessed by the ratios PINP/CTX and

PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II

in the whole population, but a slight decrease (ANOVA p = 0.041) in

those with pre-treatment levels above the upper limit of normal range.

Conclusions: In summary, the improvement in the formation/resorption

marker ratio suggests beneficial systemic and local bone effects of

infliximab in patients with RA.

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http://ard.bmj.com/cgi/content/abstract/67/3/353?etoc

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