Title
Markers for Type II Collagen Breakdown Predict the Effect of Disease-Modifying Treatment on Long-Term Radiographic Progression in Patients with Rheumatoid Arthritis
Author
TNO Preventie en Gezondheid
Landewé, R.
Geusens, P.
Boers, M.
van der Heijde, D.
Lems, W.
te Koppele, J.
van der Linden, S.
Garnero, P.
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 (beta = 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 (
Subject
c terminal crosslinking telopeptide of type 1 collagen
c terminal crosslinking telopeptide of type 2 collagen
methotrexate
prednisolone
salazosulfapyridine
unclassified drug
controlled study
creatinine urine level
disease activity
disease course
disease marker
drug efficacy
drug megadose
follow up
inflammation
joint radiography
linear regression analysis
low drug dose
major clinical study
monotherapy
scoring system
urinalysis
Adult
Anti-Inflammatory Agents
Antirheumatic Agents
Arthritis, Rheumatoid
Biological Markers
Collagen
Collagen Type I
Collagen Type II
Disease Progression
Drug Therapy, Combination
Female
Humans
Male
Methotrexate
Middle Aged
Peptides
Prednisolone
Sulfasalazine
To reference this document use:
http://resolver.tudelft.nl/uuid:f2e956f5-2313-4576-8be9-7a649dde9d7d
DOI
https://doi.org/10.1002/art.20222
TNO identifier
237748
ISSN
0004-3591
Source
Arthritis and Rheumatism, 50 (50), 1390-1399
Document type
article