Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis.

Abstract

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 alpha (TNFalpha). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFalpha 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.

• Authors: F Chopin, P Garnero, A le Henanff, F Debiais, A Daragon, C Roux, J Sany, D Wendling, C Zarnitsky, P Ravaud, T Thomas
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 67 Issue 3 Pg. 353-7 (Mar 2008) ISSN: 1468-2060 [Electronic] England
• PMID: 17644538 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antirheumatic Agents
• Biomarkers
• Tumor Necrosis Factor-alpha
• Infliximab

Topics

• Absorptiometry, Photon
• Adult
• Aged
• Antibodies, Monoclonal (pharmacology)
• Antirheumatic Agents (pharmacology)
• Arthritis, Rheumatoid (drug therapy, metabolism, physiopathology)
• Biomarkers (metabolism)
• Bone Density (drug effects)
• Bone Remodeling (drug effects)
• Bone Resorption (metabolism, physiopathology, prevention & control)
• Cartilage, Articular (drug effects, physiopathology)
• Female
• Hip Joint (drug effects, physiopathology)
• Humans
• Infliximab
• Lumbar Vertebrae (drug effects, physiopathology)
• Middle Aged
• Prospective Studies
• Severity of Illness Index
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)