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Markers for Type II Collagen Breakdown Predict the Effect of Disease-Modifying Treatment on Long-Term Radiographic Progression in Patients with Rheumatoid Arthritis
- Publication Year :
- 2004
-
Abstract
- Objective. To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid arthritis (RA). Methods. Patients had participated in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) trial comparing aggressive step-down combination therapy (the COBRA regimen, including temporary high-dose prednisolone, temporary low-dose methotrexate, and sulfasalazine [SSZ]) and mild monotherapy (SSZ). Urinary CTX-I and CTX-II levels were measured at baseline and 3, 6, 9, and 12 months after initiation of treatment. Radiographs were scored according to the modified Sharp/van der Heijde method (mean of 2 independent readers who were aware of the sequence). Individual long-term radiographic progression was estimated, using baseline radiographs and all radiographs obtained during the followup period, by simple linear regression analysis (curve fitting). Results. Both COBRA therapy and SSZ monotherapy produced a significant decrease in urinary CTX-I and CTX-II levels at 3 months, and this decrease was amplified at 6 months. COBRA therapy suppressed CTX-II (change from baseline levels -36% and -43% at 3 and 6 months, respectively), but not CTX-I, significantly better than did SSZ (-17% and -21% at 3 and 6 months, respectively) at 3 and 6 months. The magnitude of the decrease in urinary CTX-II levels at 3 months significantly predicted long-term (5-year) radiographic progression (β = 0.48 [95% confidence interval (95% CI) 0.13, 0.83]). This effect was independent of the change in disease activity and inflammation indices at 3 months. Patients whose CTX-II levels were normalized (
- Subjects :
- Adult
Male
drug megadose
c terminal crosslinking telopeptide of type 1 collagen
urinalysis
Prednisolone
Anti-Inflammatory Agents
salazosulfapyridine
methotrexate
Collagen Type I
low drug dose
disease marker
Drug Therapy
Rheumatoid
joint radiography
follow up
Humans
controlled study
Collagen Type II
disease course
Arthritis
scoring system
Middle Aged
major clinical study
unclassified drug
drug efficacy
Sulfasalazine
c terminal crosslinking telopeptide of type 2 collagen
inflammation
creatinine urine level
monotherapy
Antirheumatic Agents
Combination
linear regression analysis
Disease Progression
Biological Markers
Female
Collagen
Peptides
disease activity
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.dris...00893..f16f95b58990cd8dd2b2b2e50e51eac2