Digital tomosynthesis as a new diagnostic tool for assessing of chronic gout arthritic feet and ankles: comparison of plain radiography and computed tomography

This aimed to compare the three radiographic methods of digital tomosynthesis (DT), plain radiography, and computed tomography (CT) for evaluating changes in feet of patients with chronic gouty arthritis. Two independent radiologists read the plain radiography, DT, and CT images of 30 male patients with gout. The degrees of erosion and joint space narrowing were scored using the Sharp–van der Heijde scoring method in 18 foot joints, which consisted of four proximal interphalangeal and one interphalangeal joint of the first toe, five metatarsophalangeal, five tarsometatarsal, and three naviculo-cuneiform joints of the foot. DT showed high reproducibility [0.929 for intraobserver intraclass correlation coefficient (ICC) and 0.838 for interobserver ICC]. DT showed similar results to those of CT and superior results to those of plain radiography for evaluating radiographic damage [mean total score, 8.5 ± 14.6 (±standard deviation) for plain radiography, 12.9 ± 12.4 for DT, and 12.6 ± 11.2 for CT]. This study showed that DT is a good method for evaluating radiographic changes in patients with gout. Further research is needed to apply DT to actual clinical settings.     

Reproducibility and sensitivity to change of 5 methods for scoring hand radiographic damage in patients with rheumatoid arthritis

OBJECTIVE: To compare intrarater and interrater reproducibility and sensitivity to change of 5 scoring methods for radiographic damage on hand radiographs in patients with rheumatoid arthritis (RA). METHODS: Radiographs of 22 patients from Norway and France with average 2 years' disease duration at baseline and mean 30 months' followup were assessed by 2 readers according to Larsen, Larsen/Rau, Sharp, Sharp/van der Heijde, and Simple Erosion Narrowing Score (SENS) methods. Reproducibility at baseline and on progression was assessed using intraclass correlation coefficients (ICC) and Bland-Altman graphs. Sensitivity to change was compared across methods by computing the country-adjusted standardized response means (SRM) ratio. RESULTS: Intrarater reproducibility varied with the reader (ICC ranging from 0.90 to 0.97), with Larsen and Larsen/Rau ranking highest. Interrater reproducibility was highest with Sharp and Sharp/van der Heijde (ICC 0.76 to 0.93). Bland-Altman graphs showed a decrease of concordance in cases of more severe damage. Sensitivity to change was higher with Sharp and Sharp/van der Heijde modified for erosions (SRM ratio 1.44 and 1.70), than with Larsen/Rau and SENS. The differences between Sharp, Sharp/van der Heijde, and Larsen were less for joint space narrowing. There was a significant reader effect (p < 0.05) in all but the Sharp method. Expressed as percentage of the maximum score, the smallest detectable difference varied between 3.5% (Sharp/van der Heijde) and 14.2% (SENS erosion). CONCLUSION: All methods have high intraobserver and interobserver reliability. The interrater reproducibility decreases with disease severity. Recent modified methods perform best to detect changes, but the advantages of SENS seemed to be lost when applied on hand radiographs alone. Training the readers appears to be essential.     

Adapted versions of the Sharp/van der Heijde score are reliable and valid for assessment of radiographic progression in juvenile idiopathic arthritis

OBJECTIVE: To develop adapted versions of the Sharp/van der Heijde radiographic scoring system for use in juvenile idiopathic arthritis (JIA), and to investigate their validity in JIA patients with polyarticular disease. METHODS: The study group comprised 177 patients with polyarticular JIA. Radiographs of the wrist/hand of each patient were obtained at baseline (first observation) and then at 1, 3, 5, 7/8, and 10 years and were assessed independently by 2 pediatric rheumatologists according to different adaptations of the Sharp/van der Heijde method. To facilitate score assignment, the radiograph for each patient was compared with a bone age-related standard. Validation procedures included analysis of reliability, construct validity, and score progression over time. RESULTS: Interobserver and intraobserver agreement on longitudinal score values and score changes was good for all of the adapted scoring versions (intraclass correlation coefficient >0.85). Score changes over time were moderately to strongly correlated with the clinical indicators of long-term joint damage and with the amount of long-term radiographic damage as measured with the carpo:metacarpal ratio, thereby demonstrating good construct validity. A steady increase in scores over time was observed, with joint space narrowing being the most common form of damage throughout the disease course. The inclusion of 5 new areas appeared to increase the overall construct validity of erosion scores. CONCLUSION: Our results show that the adapted versions of the Sharp/van der Heijde score are reliable and valid for the assessment of radiographic progression in patients with JIA.     

Prediction of radiographic progression in synovitis-positive joints on maximum intensity projection of magnetic resonance imaging in rheumatoid arthritis

Contrast-enhanced magnetic resonance imaging with maximum intensity projection (MRI-MIP) is an easy, useful imaging method to evaluate synovitis in rheumatoid hands. However, the prognosis of synovitis-positive joints on MRI-MIP has not been clarified. The aim of this study was to evaluate the relationship between synovitis visualized by MRI-MIP and joint destruction on X-rays in rheumatoid hands. The wrists, metacarpophalangeal (MP) joints, and proximal interphalangeal (PIP) joints of both hands (500 joints in total) were evaluated in 25 rheumatoid arthritis (RA) patients. Synovitis was scored from grade 0 to 2 on the MRI-MIP images. The Sharp/van der Heijde score and Larsen grade were used for radiographic evaluation. The relationships between the MIP score and the progression of radiographic scores and between the MIP score and bone marrow edema on MRI were analyzed using the trend test. As the MIP score increased, the Sharp/van der Heijde score and Larsen grade progressed severely. The rate of bone marrow edema-positive joints also increased with higher MIP scores. MRI-MIP imaging of RA hands is a clinically useful method that allows semi-quantitative evaluation of synovitis with ease and can be used to predict joint destruction.     

Radiographic damage of large joints in long-term rheumatoid arthritis and its relation to function

OBJECTIVE: To describe the extent of radiographic damage of large joints in long-term rheumatoid arthritis (RA) and its relationship to small joint involvement and physical function. METHODS: After 12 yr of follow-up, radiographs of all large joints (Larsen large joint score 0-60) of 105 recent RA patients were assessed. Correlations were evaluated between the Larsen large joint score and radiographic damage of the hands and feet as measured by the van der Heijde modification of the Sharp score (SHS) and the health assessment questionnaire (HAQ). We determined the relative contributions of radiographic damage of small and large joints, disease activity and psychological function to the HAQ. RESULTS: The median Larsen large joint score was 3. In 54% of the patients at least one large joint was erosive. The correlation of the Larsen score with the SHS and HAQ scores was 0.76 and 0.60, respectively. Disease activity and radiographic damage of the large joints were the major determinants of the HAQ score. CONCLUSION: Large joint involvement after 12 yr of follow-up is extensive and is associated with functional disability. Large joint involvement is closely associated with small joint involvement.     

Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: Results from the induction and maintenance psoriatic arthritis clinical trial 2

OBJECTIVE: To evaluate the effect of infliximab on progression of structural damage over 1 year in patients with active psoriatic arthritis (PsA) enrolled in the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2. METHODS: In this double-blind, placebo-controlled study, 200 patients with active PsA were randomly assigned (1:1 ratio) to receive infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, and 6, and every 8 weeks thereafter through week 54. At week 24, patients initially assigned to receive placebo crossed over to receive infliximab (5 mg/kg). Based on predefined criteria, patients randomized to receive placebo could enter early escape by receiving infliximab (5 mg/kg) starting at week 16, and patients randomized to receive infliximab could have the dose increased to 10 mg/kg starting at week 38. Patients were analyzed according to the treatment they were randomized to receive. Radiographs of hands and feet were obtained at baseline and at weeks 24 and 54. Two readers blinded to treatment assignment and radiograph sequence independently evaluated erosions and joint space narrowing using the Sharp/van der Heijde scoring method modified for PsA. RESULTS: At week 24, patients randomized to receive infliximab 5 mg/kg had significantly less radiographic progression compared with patients randomized to receive placebo, with mean +/- SD changes from baseline in the total Sharp/van der Heijde score of -0.70 +/- 2.53 and 0.82 +/- 2.62, respectively (P < 0.001). At week 54, mean +/- SD changes from baseline in the total Sharp/van der Heijde score were -0.94 +/- 3.40 in patients randomized to receive infliximab and 0.53 +/- 2.60 in those receiving placebo/infliximab (P = 0.001). CONCLUSION: Infliximab significantly inhibits radiographic progression in patients with PsA as early as 6 months after starting treatment, and the beneficial effect continues through 1 year of infliximab therapy.     

Long term evaluation of radiographic disease progression in a subset of patients with rheumatoid arthritis treated with leflunomide beyond 2 years

OBJECTIVES: To assess the effect of long term (>2 years) leflunomide treatment on radiographic progression in patients with RA. METHODS: Patients treated with leflunomide for >2 years in one of three phase III trials and subsequent extensions, for whom paired, evaluable radiographs at baseline and study end point were available, were included. Radiographs of hands and feet were assessed according to the modified Sharp/van der Heijde scoring method, for erosion, joint space narrowing, and total score. Changes from baseline were assessed, and a predicted yearly progression rate estimated for each patient. RESULTS: 128 of the original 824 patients were included, with mean disease duration 5.1 years and mean leflunomide treatment duration 4.3 years until the final x ray examination. The mean change from baseline in total score was 8.6 with yearly adjusted rate 1.9, and the median change was 2 with yearly adjusted rate 0.5, compared with 7.9 and 4.9, respectively, before leflunomide treatment. After treatment, the rate improved in 92/128 (72%) patients and deteriorated in 21/128 (16%). In 42 (33%) patients who had a total score >0 at baseline, no radiographic progression occurred after leflunomide treatment. CONCLUSIONS: In a subset of patients who continued treatment long term, leflunomide treatment reduced the rate of radiographic damage.     

Minimal clinically important difference in radiological progression of joint damage over 1 year in rheumatoid arthritis: preliminary results of a validation study with clinical experts

To determine the minimal clinically important difference (MCID) between hand and foot films with a 1 year interval assessed with the Sharp/van der Heijde or Larsen/Scott scoring method. Progression scores of the 2 methods were compared with the opinion of an international expert panel on clinical relevance of radiological joint damage in 4 predefined clinical settings. The expert panel consisted of 3 rheumatologists, who evaluated 46 pairs of hand and foot films, taken with 1 year intervals, of patients with early rheumatoid arthritis. Receiver operating characteristics curves analyzed the accuracy of different threshold values (progression scores) of the 2 scoring methods to detect the presence or absence of clinically important difference, as defined by the expert panel as external criterion. The threshold value with the highest accuracy was subsequently chosen as the score representing the MCID. Five Sharp/van der Heijde units and 2 Larsen/Scott units were the best cutoffs. The accompanying sensitivities ranged from 77% to 100% for the Sharp/van der Heijde method and from 73% to 84% for the Larsen/Scott method for the 4 clinical settings. The specificities were between 78% and 84% for the Sharp/van der Heijde method and between 74% and 94% for the Larsen/Scott method. The smallest progression score that can be detected apart from interobserver measurement error, the smallest detectable difference (SDD), was equal to or larger than the calculated MCID, 5 Sharp/van der Heijde units and 6 Larsen/Scott units in our study, if the mean progression scores of the same 2 observers were used. The SDD is a conservative estimate of the MCID; our panel rated progression at or below this level as clinically significant.     

Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis.

OBJECTIVE: To determine the reliability and sensitivity to change of a simplified radiological scoring method [simple erosion narrowing score (SENS)] for rheumatoid arthritis (RA). SENS was compared to the Sharp/van der Heijde score (SHS) as a gold standard. METHODS: Sets of seven radiographs of hands and feet were taken of 20 RA patients with a wide spectrum of radiological damage. For 14 patients, these seven radiographs were taken during a follow-up period of 5 yr, and for six patients during a follow-up of 10 yr. Each set of radiographs was scored twice by the same observer (DvdH). Erosions and joint space narrowing were scored with SHS (range 0-448) in 32 and 30 joints in the hands, respectively, and both in 12 joints in the feet. SENS gives a score of 1 if there is any erosion in a joint and also 1 if there is any narrowing in the joint (range 0-86). In each case, SENS was derived from SHS. To analyse data, generalizability theory and repeated measurements ANOVA were used. RESULTS: The overall reliability coefficient was 0.81 for SHS and 0.80 for SENS. Intra-observer reliability [intraclass correlation coefficient (ICC)] was 0.99 and 0.98 for SHS and SENS, respectively. The ICC for the sensitivity to change was 0.84 for SHS and 0.88 for SENS. The smallest detectable difference (SDD) could be determined for both methods. The presence of progression based on this SDD was very comparable between the two methods. CONCLUSION: The measurement properties of SENS are good and comparable to SHS. This makes SENS suitable for use in clinical practice and in large (epidemiological) studies, especially in the first years of disease.     

An overview of radiographic analysis of joint damage in rheumatoid arthritis and its use in metaanalysis

A brief history of the development of scoring methods to represent the extent of radiographic abnormalities in rheumatoid arthritis shows that grading systems have become more detailed with time. Taken together with the observation that physicians continue to modify scoring methods it is clear that we have not yet arrived at the ideal method. Issues to be considered in evaluating scoring methods include which abnormalities and which joints to score and what scale to use. Data from one early trial indicate that erosion and joint space narrowing scores do not progress in lockstep and progression in one does not predict progression in the other; this leads to the conclusion that including both features in a scoring method is important. Data from the same trial raise the possibility that joint space narrowing scores for the proximal interphalangeal finger joints may not be helpful in detecting treatment differences, illustrating that further investigation of which joints to include in scoring is needed. The possibility that an expanded scoring scale might be more sensitive to recording a change in radiographic damage also was raised. A simple method of determining which patients show progression of damage was proposed based on assessing the distribution of negative progression scores (baseline erosion scores subtracted from followup scores adjusted for time). It was pointed out that radiographic assessment has established that a few drugs slow the progression of joint damage. Radiographic evaluation of disease progression should continue to be utilized as an outcome measure in evaluating new therapies.     

Prognostic factors for joint destruction in rheumatoid arthritis: a prospective longitudinal study of 318 patients

OBJECTIVE: To quantify articular damage and to investigate prognostic factors for joint damage progression in rheumatoid arthritis (RA). METHODS: RA patients satisfying the 1987 American College of Rheumatology criteria and with disease duration under 5 years were sampled from the EURIDISS longitudinal cohort study in Norway, The Netherlands, and France. Hand radiographs were assessed at baseline and at 2 to 3 year followup using Sharp score modified by van der Heijde. Assessment of erosion and joint space narrowing, performed in sequential order by a single reader blinded to patients' characteristics, had high intraobserver reproducibility (intraclass correlation coefficient 0.98-0.99). Baseline prognostic factors were analyzed in a multivariate linear regression model. RESULTS: A total of 318 patients with RA aged 52.4 years (70.4% were female) and with a mean 2 years' disease duration at baseline were followed over 30 months. Median (quartiles) baseline and followup modified Sharp scores were 3 (0-11) and 9 (1-27), respectively, with 35.8% and then 22.3% of patients with no radiological damage. Controlling for age, sex, and country, the final joint damage was predicted by baseline modified Sharp score, rheumatoid factor positivity, time from disease diagnosis, patient global health assessment, and erythrocyte sedimentation rate, and by followup duration, explaining 76.8% of the outcome variance. CONCLUSION: This multinational study confirmed the prognostic role in RA of a set of features previously identified in smaller cohorts. It indicates which disease characteristics should be focused on in the early years of RA to identify patients at higher risk of developing severe disease and who are candidates for aggressive therapy.     

Ultrasonographic and radiographic results from a two-year controlled trial of immediate or one-year-delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis

OBJECTIVE: To compare the impact of immediate and delayed introduction of anti-tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). METHODS: Twenty-four patients with erosive early RA (duration < 3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high-frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system. RESULTS: From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between-group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076). CONCLUSION: The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.     

Association of early radiographic damage with impaired physical function in rheumatoid arthritis: a ten-year, longitudinal observational study in 238 patients

OBJECTIVE: To investigate the longitudinal relationship between physical disability, disease activity, and radiographic damage over 10 years in patients with rheumatoid arthritis (RA). METHODS: A cohort of 238 consecutively enrolled RA patients from the European Research on Incapacitating Disease and Social Support study (age range 20-70 years, mean disease duration 2.3 years, 68% rheumatoid factor [RF] positive) was followed up longitudinally for 10 years. Assessments at baseline and at years 1, 2, 5, and 10 comprised review of demographic variables, measurement of disease activity with the erythrocyte sedimentation rate (ESR), functional evaluations using the Health Assessment Questionnaire (HAQ) and grip strength (average value of the right and left hand), and radiographs of the hands scored by the van der Heijde modification of the Sharp method. Marginal modeling by generalized estimating equations was used to study the longitudinal relationship between the ESR and modified Sharp radiographic damage score with respect to explaining the HAQ score and grip strength. Age, sex, RF status, and disease duration were entered as covariates. RESULTS: The HAQ score and grip strength were longitudinally associated with the momentary modified Sharp/van der Heijde score as well as with progression in this score, independent of the ESR. Therefore, an increase of 10 units in the modified Sharp/van der Heijde score will result in a 0.03-unit increase in HAQ score and a 0.95-kg decrease in grip strength, after adjustment for the ESR. CONCLUSION: This 10-year observational study provides evidence that both radiographic damage and disease activity are independent contributors to impaired physical function in RA, both early and late in the disease process.     

The course of radiologic damage during the first six years of rheumatoid arthritis

OBJECTIVE: To describe the radiologic course in a large cohort of patients with early rheumatoid arthritis (RA) and to analyze individual components of damage. METHODS: Five hundred two patients with recent-onset RA (disease duration <1 year) underwent annual radiologic assessment for a maximum of 6 years in this longitudinal prospective study. The study was designed to investigate the efficacy of 3 different therapeutic strategies. For the assessment of radiologic damage, radiographs of the hands and feet were scored according to the modified Sharp/van der Heijde method (SHS; range 0-448). A mean of 2.9 (range 1-7) radiographs was read per patient. RESULTS: Stable rates of progression of the SHS, erosion score, and narrowing score were found over the course of RA: the mean rates were 8.6, 5.4, and 3.2 modified Sharp units per year, respectively. The rate of progression of newly (not previously) damaged joints declined, and the rate of progression of already damaged joints (which became more damaged) increased during followup, leading to an equal contribution to progression of the SHS at 5 years. The joints of the feet, especially the fifth metatarsophalangeal joint, generally became eroded earlier and more of them became eroded compared with the joints of the hands. CONCLUSION: Radiologic damage progresses at a constant rate. In advanced disease, monitoring the progression of previously existing damage is as important as assessing new abnormalities in previously undamaged joints. Radiographs of the feet should be included in assessments of radiologic damage that are used in clinical intervention trials and daily practice.     

Radiographic study on the pattern of wrist joint destruction in rheumatoid arthritis

When planning therapy for rheumatoid arthritis (RA) in the wrist joint, knowing the pattern of joint destruction is important. There were a few studies using the Larsen and modified Larsen method to evaluate RA wrist joint destruction. However, these methods are inadequate for thoroughly assessing the severity of joint destruction because joint bone erosion and joint space narrowing could not be evaluated individually in these methods. To clarify the pattern of RA wrist joint destruction in the different zones of the wrist, we conducted a large-scale radiographic study. We modified the van der Heijde/Sharp method to assess radiographic images. Subjects were 191 RA patients (22 men and 169 women; mean age 57.0 years) who were examined at our center between 2001 and 2003 and underwent plain X-ray of both wrist joints (n = 382). Using X-ray images of the wrist joint, classification was performed based on the severity of wrist joint surface bone erosion and joint space narrowing at different zones, and the results were statistically analyzed. The results showed that joint space narrowing in the midcarpal joint (MCJ) advanced faster than in the radiocarpal joint (RCJ). Conversely, bone erosion in the RCJ advanced faster than in the MCJ. In X-ray diagnosis of RA wrist joint disorders, knowing the pattern of destruction is useful for assessing the presence or absence of early joint destruction and in planning therapy.     

Radiographic hand joint space width assessed by computer is a sensitive measure of change in early rheumatoid arthritis

OBJECTIVE: To compare changes in the computerized measurement of radiographic hand joint space width (JSW) to changes in modified Sharp scores in a retrospective 2-year study of early rheumatoid arthritis (RA). METHODS: First and last standard clinical hand radiographs of 245 patients with RA were analyzed blind using purpose-written computer software to measure changes in JSW for proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in the 3 middle fingers of each hand. Before measurement, the radiographs were scored independently by 2 radiologists using a modification of Sharp scoring. RESULTS: The paired changes in JSW (-0.051 +/- 0.005 mm) and Sharp score (+3.81 +/- 0.50) were both significant over the study duration. In measured joints showing an increase in joint space narrowing (JSN) score, 92% had a corresponding reduction in JSW. In patients with an increase in total score, including JSN and erosion scores in fingers and wrists, 84% had a corresponding reduction in mean (PIP + MCP) JSW. Patients with no change in Sharp score (47%) still experienced a significant reduction in measured JSW (-0.027 +/- 0.006 mm). HLA-DR genetic markers of severe disease progression were associated with significantly greater reductions in JSW but not increases in Sharp score. (Values: mean +/- standard error of mean). CONCLUSION: Measured JSW averaged over 6 PIP and 6 MCP joints was a valid and more sensitive measure of change than total Sharp score in this study of early RA.     

Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage

OBJECTIVE: To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). METHODS: 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. RESULTS: Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years. CONCLUSION: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.     

Determination of the minimal clinically important difference in rheumatoid arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring methods by clinical experts and comparison with the smallest detectable difference

OBJECTIVE: To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method. METHODS: The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID. RESULTS: The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%). CONCLUSION: This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change.     

Metodología de presentación de los resultados de progresión radiológica en estudios clínicos

Recent clinical trials that evaluate treatment effectiveness in rheumatoid arthritis assess clinical response and progression of structural damage to joints by calculating radiographic progression over a given time period. In this article, we review three important features that have recently been developed in the methodology of scoring progression: presentation of radiographic data in clinical trials, following the preliminary guideline of van der Heijde, established in 2002, and additional new concepts such as estimated yearly progression rates and probability plots.     

A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs

The aim of this study was to evaluate the predictive value of biological, radiological and clinical parameters for the progression of radiographic joint damage in rheumatoid arthritis (RA) patients treated with conventional disease-modifying anti-rheumatic drugs (DMARDs). We analyzed the 145 patients with active RA for less than 5 years who were participating in the prospective 1-year randomized controlled trial of tocilizumab (SAMURAI trial) as a control arm treated with conventional DMARDs. Progression of joint damage was assessed by sequential radiographs read by two independent blinded X-ray readers and scored for bone erosion and joint space narrowing (JSN) using the van der Heijde-modified Sharp method. Multivariate analysis revealed that increased urinary levels of C-terminal crosslinked telopeptide of type II collagen (U-CTX-II), an increased urinary total pyridinoline/total deoxypyridinoline (U-PYD/DPD) ratio and low body mass index (BMI) at baseline were independently associated with a higher risk for progression of bone erosion. In addition to these three variables, the JSN score at baseline was also significantly associated with an increased risk of progression of the JSN score and total Sharp score. High baseline U-CTX-II levels, U-PYD/DPD ratio and JSN score and a low BMI are independent predictive markers for the radiographically evident joint damage in patients with RA treated with conventional DMARDs.