Predictors of radiographic joint damage in patients with early rheumatoid arthritis

166

Objective. The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA.Methods. This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers).Results. In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >4, n ‫؍‬ 49) and absence (Sharp score <4, n ‫؍‬ 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively).Conclusion. High baseline levels of urinary CTX-I and CTX-II independently predict an increased risk of radiologic progression over 4 years in patients with early RA, especially those without radiologic joint damage. Urinary CTX-I and CTX-II may be useful for identifying individual RA patients at high risk of progression very early in the disease, before erosions can be detected radiographically. Such patients may be in special need of treatments that inhibit bone and cartilage degradation.

Section: Prediction Of Joint Damage In Early Ra By Bone and Cartilagesupporting

confidence: 91%

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confidence: 99%

Association of baseline levels of markers of bone and cartilage degradation with long‐term progression of joint damage in patients with early rheumatoid arthritis

Garnero¹,

Landewé²,

Boers³

et al. 2002

166

“…This study encompassed a relatively short period of observation, and the changes in radiographic progression seen over 1 year may not necessarily extrapolate to longer observation periods. However, a large body of evidence exists to support the relationship between elevated values of composite disease activity indices, ESR and CRP levels, and radiographic progression in RA patients over many years of observation (7,8,(10)(11)(12)(13)43). Moreover, our findings in the present study are similar to results of a subanalysis from the Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial involving patients with longstanding RA (44).…”

Section: Discussionmentioning

confidence: 99%

“…While progression of radiographic abnormalities may have limited implications with regard to function in the short term, accumulation of destruction over time translates into a decline of functional capacity and quality of life (4)(5)(6). Both functional decline and radiographic progression have been strongly associated with continued disease activity as reflected by persistent elevations in swollen joint counts, the acute-phase response, or disease activity scores derived from composite indices (4,(6)(7)(8)(9)(10)(11)(12)(13). These relationships have been established from previous studies of the natural course of RA and from results of clinical trials of treatments that are no longer the standard of care (14)(15)(16).…”

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confidence: 99%

Predictors of joint damage in patients with early rheumatoid arthritis treated with high‐dose methotrexate with or without concomitant infliximab: Results from the ASPIRE trial

Smolen

Heijde

Clair

et al. 2006

403

254

Objective. To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX.Methods. Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54.Results. C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (>3 mg/dl) and ESR (>52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS >10.5) showed less progression with infliximab plus MTX compared with MTX alone (؊0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab.Conclusion. High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiv-

“…Patients who fail to enter clinical remission can have significant levels of ongoing inflammation, despite meeting currently accepted treatment response criteria (4,7). Other prognostic factors, including the presence of rheumatoid factor, rheumatoid nodules, HLA-DR4/ shared epitope, and anti-cyclic citrullinated peptide antibodies (9)(10)(11)(12), are associated with worse outcomes when using grouped data, but they are not useful in predicting individual outcomes or responses to therapy. New biomarkers are therefore needed that can predict and be used to help prevent long-term radiographic progression in individual patients.…”

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confidence: 99%

Early changes in serum type ii collagen biomarkers predict radiographic progression at one year in inflammatory arthritis patients after biologic therapy

Mullan¹,

Matthews²,

Bresnihan³

et al. 2007

Objective. To investigate whether short-term changes in serum biomarkers of type II collagen degradation (C2C) and types I and II collagen degradation (C1,2C), as well as the biomarker for the synthesis of type II procollagen (CPII) can predict radiographic progression at 1 year following initiation of biologic therapy in patients with inflammatory arthritis.Methods. Serum levels of biomarkers were measured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflecting changes from baseline in all 3 biomarkers (⌬COL) was calculated. Associations with clinical responses according to the 28-joint count Disease Activity Score and with radiographic progression according to the modified Sharp/van der Heijde score (SHS) were assessed.Results. The 1-year increase in the SHS correlated with the 1-month change in C2C results (r ‫؍‬ 0.311, P ‫؍‬ 0.028) and the ⌬COL score (r ‫؍‬ 0.342, P ‫؍‬ 0.015). Radiographic progression was predicted by increases in serum C2C at 1 month (P ‫؍‬ 0.031). The ⌬COL score was significantly associated with 1-year radiographic progression after 1 (P ‫؍‬ 0.022), 3 (P ‫؍‬ 0.015), 6 (P ‫؍‬ 0.048), and 9 (P ‫؍‬ 0.019) months of therapy. Clinical remission was predicted by 1-month decreases in serum levels of C2C (P ‫؍‬ 0.008) and C1,2C (P ‫؍‬ 0.036). By regression analysis, 1-month changes in C2C, C1,2C, and CPII levels were independently associated with, and correctly predicted radiographic outcome in, 88% of the patients.Conclusion. Short-term changes in serum levels of collagen biomarkers following initiation of biologic therapy may better predict long-term clinical and radiographic outcomes. These collagen biomarkers may therefore be valuable new early indicators of short-term biologic treatment efficacy in clinical trials and in individual patients with inflammatory erosive arthritis.Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are forms of progressive inflammatory arthritis characterized by pain and progressive destruction of the joints. Joint destruction occurs when inflamed synovial tissue erodes and degrades adjacent cartilage and bone through the action of locally produced cytokines and metalloproteinases (1). This process can be measured by quantifying the changes in joint space narrowing and erosions that are visible on serial plain radiographs (2). Radiographic joint damage is associated with long-term functional disability (3) and is the accepted assessment tool for monitoring clinical progression and long-term response to therapy (4). Radiographic progression develops over many months and years, however, and is not suitable for assessment of treatment efficacy over short periods.