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OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that may result in debilitating joint deformities with destruction of bone and cartilage. Inflammation is still considered the pivotal inducer of both components of joint damage. Results of recent animal studies suggested a prominent contribution of osteoclastic bone resorption that could be dissociated from inflammation. RANKL and its natural decoy receptor, osteoprotegerin (OPG), play key roles in osteoclast activation. In a group of patients with early RA not treated with disease-modifying drugs, we tested the hypothesis that osteoclast activation, reflected by the serum OPG:RANKL ratio at baseline, is negatively associated with progression of bone damage, independent of inflammation. METHODS: OPG and RANKL levels, together with a parameter of inflammation (first-year time-averaged erythrocyte sedimentation rate [tESR]), were measured in 92 patients with newly diagnosed early active RA who were participants in a randomized study. The tESR and the OPG:RANKL ratio were evaluated for the ability to predict 5-year radiographic progression of joint damage. RESULTS: The first-year tESR and the OPG:RANKL ratio, as measured at baseline, independently predicted 5-year radiographic progression of joint damage (both P

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 receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti-tumor necrosis factor alpha [anti-TNFalpha] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of < or =3 years' duration. METHODS: RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX-placebo, MTX-3 mg/kg infliximab, and MTX-6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. RESULTS: At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean +/- SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 +/- 5.8 and 0.5 +/- 5.6 versus 3.7 +/- 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia. CONCLUSION: For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials. METHODS: The validity of the currently available methods, the Bath Ankylosing Spondylitis Radiology Index (BASRI), the Stoke Ankylosing Spondylitis Spine Score (SASSS), and the modified SASSS (M-SASSS), was tested according to the aspects of the Outcome Measures in Rheumatology Clinical Trials filter: truth, discrimination (reliability and sensitivity to change), and feasibility, using radiographs of 133 patients at 4 different time points (baseline, 1 year, 2 years, and 4 years). One observer scored these sets in chronological order. To assess interobserver reliability, a second observer scored radiographs of 20 patients at the 4 different time points. RESULTS: After 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, approximately 40% of patients showed changes in both the lumbar and cervical spine. Therefore, it was concluded that, for the assessment of progression, SI joints and hips are of minor importance. The intraclass correlation coefficient (ICC) varied from 0.87 to 0.98 and ICCs for intraobserver scores varied from 0.96 to 0.99. Concerning progression scores, only the ICC for the M-SASSS measured after 2 years remained acceptable (0.82). The intraobserver scores for progression after 2 years of followup were an ICC of 0.93 for the BASRI, an ICC of 0.79 for the SASSS, and an ICC of 0.95 for the M-SASSS. Concerning sensitivity to change, it was found that the M-SASSS classified the highest percentage of patients with a change >0. CONCLUSION: The M-SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients. [ABSTRACT FROM AUTHOR]