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To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials.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.After 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, ∼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.The M‐SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials. [ABSTRACT FROM AUTHOR]

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.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, time2 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. Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time2 −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. 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]

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). 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). 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 (<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]). 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. [ABSTRACT FROM AUTHOR]