Markers for type II collagen breakdown predict the effect of DMARD treatment on radiographic progression in patients with RA

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Arthritis Rheum. 2004 May;50(5):1390-9.

Markers for type II collagen breakdown predict the effect of

disease-modifying treatment on long-term radiographic progression in

patients with rheumatoid arthritis.

Landewe R, Geusens P, Boers M, van der Heijde D, Lems W, te Koppele J,

van der Linden S, Garnero P.

Department of Internal Medicine/Rheumatology, University Hospital

Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands.

Rlan@...

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

Reumatoide 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 (<150 ng/mmoles of urinary creatinine) at

3 months had a significantly higher chance of radiographic stability (no

progression over 5 years) than did patients whose CTX-II levels were

increased both at baseline and at 3 months (odds ratio 4.5 [95% CI 1.5,

13]).

CONCLUSION: The individual CTX-II response measured after 3 months of

therapy in patients with active RA who had increased CTX-II levels at

baseline independently predicts long-term radiographic progression.

Urinary CTX-II levels may be used as early markers of treatment efficacy

in patients with RA.

PMID: 15146408

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