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.     

Comparison of radiological severity in psoriatic arthritis and rheumatoid arthritis

OBJECTIVE: To compare the radiological severity of patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA). METHODS: Patients were identified from the University of Toronto PsA and RA databases. Using the earliest available radiographs, each RA patient was matched to a single PsA patient on the basis of sex, age, and disease duration. Two rheumatologists blinded to the patient's diagnosis scored the radiographs using the modified Steinbrocker method. RESULTS: PsA and RA groups were similar with respect to demographics as well as the use of disease modifying antirheumatic medications. No significant difference in Steinbrocker score for the hands and feet or the hands only was noted. Patients with RA had a higher radiological score in the feet. The 2 groups were similar in the number of joints with significant radiological damage (Steinbrocker 3 and 4). CONCLUSION; Overall the radiological severity in the hands and feet of patients with PsA was comparable to that of patients with RA.     

Ability of foot radiographs to predict rheumatoid arthritis in patients with early arthritis

OBJECTIVE: In a cohort of patients with early arthritis, to evaluate how well foot radiographs at study inclusion predicted a diagnosis of rheumatoid arthritis (RA) 2 years later. METHODS: A cohort of patients with arthritis of less than one year duration was evaluated in a multicenter study and followed for 30 +/- 11 months. An observer blinded to patient data read all 149 hand and foot radiographs done at study inclusion, using item 7 of the 1987 American College of Rheumatology (ACR) criteria for RA and Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for the 1987 ACR item 7 was 0.52 for bony decalcification and 0.87 for erosions. Intra and interobserver correlation coefficients for Sharp's scores ranged from 0.90 to 0.98. Erosions at the feet were significantly associated with RA. The item 7 erosion component at the feet was more specific than the full item 7 (97.5% vs 94%; p = 0.01). Sharp's erosion score at the feet was not better than the erosion component of item 7 (sensitivity 18%; specificity 97.5%). Combined use of radiographs of the hands and feet improved the diagnostic performance of the item 7 erosion component; (sensitivity and specificity of item 7 erosions at the hands combined with the feet were 32.5% and 94.5%, respectively). CONCLUSION: The "erosion" criterion at the feet had the best diagnostic performance and was significantly associated with a diagnosis of RA. Combining hand and foot radiographs improved diagnostic performance.     

The 5-yr HAQ-disability is related to the first year's changes in the narrowing, rather than erosion score in patients with recent-onset rheumatoid arthritis

OBJECTIVE: To evaluate the predictive validity of radiological change on 5-yr disability in rheumatoid arthritis (RA). METHODS: The study was designed to be multicentre, prospective, longitudinal, with a 5-yr follow-up. Participants were RA patients (ACR criteria), with a disease duration of <1 yr at entry. Radiographs of the hands and feet in posteroanterior view at baseline and after 12 months of follow-up (van der Heijde's modification of Sharp method) were used for structural evaluation. Disability was evaluated with Health Assessment Questionnaire (HAQ) at yr 5. Analyses consisted of (i) correlation existing between the changes in the radiological scores during the first year and the HAQ value at yr 5 and (ii) determination of the optimal cut-off in the changes in the radiological scoring system, by ROC curve analysis, in which variable to be explained was disability status at yr 5, defined by HAQ value of at least 1. RESULTS: Due to missing data and/or lost to follow-up, 135 patients (out of the 191 recruited patients) were included in the analyses (mean change in the radiological score = 4.9 +/- 8.7 points, mean HAQ at yr 5 = 0.62 +/- 0.68). There was a statistically significant correlation between the HAQ-disability status at yr 5 and the changes observed in the radiological total damage and narrowing scores during the first year (r = 0.18, P = 0.046 and r = 0.25, P = 0.006, respectively). Conversely, the short-term changes in the erosion score were not correlated with subsequent HAQ-disability (r = 0.084, P = 0.36). A change of at least 2 points in the total X-ray score was considered as optimal (sensitivity, specificity, positive and negative predictive values of 66.7, 53.9, 32.8 and 82.8%, respectively). CONCLUSION: This work shows that early changes in joint damage in patients with recent-onset RA are related to subsequent HAQ-disability. This relationship is due to changes in narrowing, rather than in erosion score, suggesting that the joint narrowing score might be of great importance in the follow-up of RA patients and in the reports of scientific results. The weak performance of the thresholds established using predictive validity for subsequent HAQ-disability compromise their use at the individual level.     

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.     

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.     

Smallest detectable difference in radiological progression

Omeract IV started a discussion on the development of radiological response criteria in rheumatoid arthritis (RA). Such criteria depend on the definition of what constitutes the minimum clinically important progression of damage. Because such a definition is currently not available, as a first step we have used the concept of random measurement error to determine what is the smallest detectable difference (SDD) in radiological progression between 2 radiographs of a particular patient. Baseline and 12 month radiographs (hands, wrists, feet) of 52 patients representative of the spectrum of radiological progression were selected from a randomized controlled trial of early rheumatoid arthritis (COBRA study) and were read paired and chronologically by 2 observers using the van der Heijde modified Sharp method (0-448 scale) and another 2 observers using the Scott modified Larsen method (0-200). The measurement error of progression was determined using the metric 95% limits of agreement method of Bland and Altman. In the setting of early RA the SDD is 11 modified Sharp score units and 8 modified Larsen score units if there is an equal distribution of baseline damage and progression in the sample and the mean score of the same trained observers is always used. The SDD is 15.5 modified Sharp score units and 11 modified Larsen score units if there is an equal distribution of baseline damage and progression in the sample and the mean score of any 2 trained observers is used. Other SDD were determined depending on the context of measurement. Although this exercise needs repetition in other settings, the SDD is a useful starting point in the development of radiological response criteria.     

Documenting damage progression in a two-year longitudinal study of rheumatoid arthritis patients with established disease (the DAMAGE study cohort): is there an advantage in the use of magnetic resonance imaging as compared with plain radiography?

OBJECTIVE: In early rheumatoid arthritis (RA), longitudinal studies have demonstrated that magnetic resonance imaging (MRI) is more sensitive than radiography in demonstrating progressive erosive joint damage. The present study evaluated the progression of erosive damage in patients with established RA by using limited field of view MRI and comparing the results with those obtained by radiography. METHODS: MRI and radiographic studies were available from 47 of 60 patients enrolled in a 2-year RA observational study. MRI of the metacarpophalangeal (MCP) joints was performed at baseline and 2 years later, and a single observer scored all of the MR images with the use of an MRI scoring method developed by the Outcome Measures in Rheumatology Clinical Trials MRI RA study group. MR images from 14 patients were reread by the same observer after 1 week to assess intraobserver reliability. Radiographs were obtained at baseline and at 2 years, and were scored by an observer using the Scott modification of the Larsen score. Radiographs from 14 patients were reread after 1 week to assess the intraobserver reliability. The smallest detectable difference (SDD) was calculated for the MRI scores, the total Larsen scores, and the Larsen scores of the dominant-hand MCP joints (MCPs 2-5) for direct comparison with the MRI results. RESULTS: The median disease duration was 5.1 years (range 0.5-29 years). Evidence of erosion progression was identified by MRI in 30 patients (64%). The SDD based on the intraobserver scores was calculated as +/-3.25 units. Using this result, 11 patients (23%) showed evidence of erosion progression on MRI that was greater than the SDD. The SDD for progression based on the intraobserver total Larsen radiographic scores was 0.77 units, and the SDD for the Larsen scores of the dominant-hand MCP joints was 1.55 units. On the basis of these results, radiographic progression was noted in 19 patients (40%) by the total Larsen score and 7 patients (15%) by the dominant-hand MCP Larsen score. The most striking finding was that although MRI and radiograph scores identified a similar group of patients as having progression of joint damage, the radiographs of both hands appeared to be more responsive to change, albeit with the caveat that radiographic progression was most marked outside the dominant-hand MCP joints. CONCLUSION: There was no clear advantage of MRI with a limited field of view as compared with radiographic imaging of both hands in detecting progression of joint damage over 2 years in this group of patients with established RA. The conclusion drawn from this study is not that radiographs are better than MRI or vice versa, but that careful analysis is required to determine the optimal imaging method, or combination of imaging methods, for each study population, depending on the objective and duration of the study.     

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.     

Documenting damage progression in a two‐year longitudinal study of rheumatoid arthritis patients with established disease (the DAMAGE study cohort): Is there an advantage in the use of magnetic resonance imaging as compared with plain radiography?

Objective

In early rheumatoid arthritis (RA), longitudinal studies have demonstrated that magnetic resonance imaging (MRI) is more sensitive than radiography in demonstrating progressive erosive joint damage. The present study evaluated the progression of erosive damage in patients with established RA by using limited field of view MRI and comparing the results with those obtained by radiography.

Methods

MRI and radiographic studies were available from 47 of 60 patients enrolled in a 2‐year RA observational study. MRI of the metacarpophalangeal (MCP) joints was performed at baseline and 2 years later, and a single observer scored all of the MR images with the use of an MRI scoring method developed by the Outcome Measures in Rheumatology Clinical Trials MRI RA study group. MR images from 14 patients were reread by the same observer after 1 week to assess intraobserver reliability. Radiographs were obtained at baseline and at 2 years, and were scored by an observer using the Scott modification of the Larsen score. Radiographs from 14 patients were reread after 1 week to assess the intraobserver reliability. The smallest detectable difference (SDD) was calculated for the MRI scores, the total Larsen scores, and the Larsen scores of the dominant‐hand MCP joints (MCPs 2–5) for direct comparison with the MRI results.

Results

The median disease duration was 5.1 years (range 0.5–29 years). Evidence of erosion progression was identified by MRI in 30 patients (64%). The SDD based on the intraobserver scores was calculated as ±3.25 units. Using this result, 11 patients (23%) showed evidence of erosion progression on MRI that was greater than the SDD. The SDD for progression based on the intraobserver total Larsen radiographic scores was 0.77 units, and the SDD for the Larsen scores of the dominant‐hand MCP joints was 1.55 units. On the basis of these results, radiographic progression was noted in 19 patients (40%) by the total Larsen score and 7 patients (15%) by the dominant‐hand MCP Larsen score. The most striking finding was that although MRI and radiograph scores identified a similar group of patients as having progression of joint damage, the radiographs of both hands appeared to be more responsive to change, albeit with the caveat that radiographic progression was most marked outside the dominant‐hand MCP joints.

Conclusion

There was no clear advantage of MRI with a limited field of view as compared with radiographic imaging of both hands in detecting progression of joint damage over 2 years in this group of patients with established RA. The conclusion drawn from this study is not that radiographs are better than MRI or vice versa, but that careful analysis is required to determine the optimal imaging method, or combination of imaging methods, for each study population, depending on the objective and duration of the study.

     

Radiographic scoring methods as outcome measures in rheumatoid arthritis: properties and advantages

BACKGROUND: Use of scored radiographs as an outcome measure can help estimate the progression of rheumatoid arthritis (RA). Radiographs not only provide permanent records with which to evaluate RA serially, but can also be randomised and blinded, a major advantage in clinical trials. OBJECTIVES AND METHOD: Medline was searched for information about the principal methods of assessing joints affected by RA. Each technique was evaluated for its measurement properties, advantages, and limitations. MAIN FINDINGS: The most commonly used methods are those devised by Sharp, Larsen, and van der Heijde/Sharp, and their variants. Methods based on the Sharp technique provide separate scores for erosion and for joint space narrowing. Larsen and variants, together with the Simple Erosion Narrowing Score (SENS) method, provide an overall score. Each method's measurement properties (feasibility, time consumption, etc) depend on the degree of detail it considers. Authors consistently recommend taking a posteroanterior view of hand and foot radiographs, and the use of trained raters. Intra- and interrater reliability values are generally higher than 0.70 (less often assessed by the intraclass correlation coefficient than the correlation coefficient). Sensitivity to change is calculated by several techniques (standardised response mean (SRM), adjusted SRM, minimal detectable change, smallest detectable difference). Most methods assessed with SRM reach a value of 0.80 or more. CONCLUSION: Standardised procedures are available for performing and reading radiographs in RA. The choice of scoring method depends on the time and staff available, and the required degree of reliability and sensitivity to change.     

A comparison of three radiologic scoring systems for the long-term assessment of rheumatoid arthritis: findings of an ongoing prospective inception cohort study of 132 women followed up for a median of twelve years

OBJECTIVE: To compare the sensitivity and efficiency of 3 different radiologic scoring systems in measuring radiologic progression of rheumatoid arthritis (RA) over a 12-year period. METHODS: Radiographs of the hands and feet of 112 RA patients were assessed at 0, 3, 6, and 12 years of disease duration using the Sharp score as modified by van der Heijde (SHS), the Sharp score with increased maximum scores (Sharp Max), and the Kellgren score. The sensitivity to change was tested using the standardized response mean (SRM); the efficiency was determined by calculating the number of patients needed to detect 50% difference in progression between 2 patient groups. RESULTS: Radiologic abnormalities were steadily progressive irrespective of the scoring method used. In early disease, the SRM was significantly larger for the SHS and Kellgren scores compared with the Sharp Max score. In late disease, the Kellgren score was slightly more sensitive to change compared with the SHS and Sharp Max scores; the difference, however, did not reach significance. In erosive disease, the SRM was significantly larger for the Kellgren compared with the SHS and Sharp Max scores. The numbers of patients needed to detect a 50% difference during the 0-3-year followup period were 129, 138, and 124 for the SHS, the Sharp Max, and the Kellgren, respectively. The numbers of patients needed to detect a 50% difference during the 6-12-year followup period were 117, 121, and 104, respectively. The numbers of patients needed to detect a 50% difference during the 6-12-year followup in patients with erosive disease were 74, 78, and 68, respectively, for the 3 scores. The Kellgren required 33 minutes to score 10 sets of radiographs of the hands and feet; the SHS score took 55 minutes. CONCLUSION: The Kellgren scoring system is the most efficient method for monitoring the radiologic progression of RA. The Kellgren and the SHS are equally sensitive to change early in the disease, whereas the Kellgren score becomes more sensitive to change late in the disease in patients with erosions.     

Clinical utility of anti-carbamylated antibody in rheumatoid arthritis female patients: Emerging predictive value compared to anti-cyclic citrullinated peptide and rheumatoid factor

Aim of the workTo evaluate the frequency of anti-carbamylated protein (anti-CarP) antibodies positivity in female rheumatoid arthritis (RA) patients; to study their association with different disease aspects clinically and radiologically and to assess their potential predictive role of RA disease compared to other autoantibodies.Patients and methodsFifty-one RA female patients and 44 age-matched controls were studied. Duration of morning stiffness, disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Laboratory investigations included acute phase reactants, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies. Conventional radiography of both hands and feet was performed and assessed by a simple erosion narrowing score (SENS). All patients were evaluated by ultrasound 7 (US7) score.ResultsThe mean age of patients was 46.9 ± 8.6 years with disease duration of 6.2 ± 5.3 years. Anti-CarP antibody was positive in 52% and 54.5% of patients seronegative for anti-CCP and RF respectively. RF was positive in 40 (78.4), anti-CCP was positive in 26(51%), and anti-CarP in 21 (41.2%) patients. Anti-CarP antibodies were significantly associated with radiological damage, DAS28, HAQ and acute phase reactants. The sensitivity and specificity were 41.2% and 88.6%, respectively for anti-CarP, 51% and 93.2% for anti-CCP and 78.4% and 90.9% for RF to diagnose RA.ConclusionsAn association between anti-CarP antibody positivity and the disease activity, severity, structural damage and hence poor disease outcome has been demonstrated. Testing anti-CarP antibodies could be a useful marker for the assessment of disease activity as well as the expectation of prognosis in RA patients.     

Long term high intensity exercise and damage of small joints in rheumatoid arthritis

OBJECTIVE: To investigate the effect of long term high intensity weightbearing exercises on radiological damage of the joints of the hands and feet in patients with rheumatoid arthritis (RA). METHODS: Data of the 281 completers of a 2 year randomised controlled trial comparing the effects of usual care physical therapy (UC) with high intensity weightbearing exercises were analysed for the rate of radiological joint damage (Larsen score) of the hands and feet. Potential determinants of outcome were defined: disease activity, use of drugs, change in physical capacity and in bone mineral density, and attendance rate at exercise sessions. RESULTS: After 2 years, the 136 participants in high intensity weightbearing exercises developed significantly less radiological damage than the 145 participants in UC. The mean (SD) increase in damage was 3.5 (7.9) in the exercise group and 5.7 (10.2) in the UC group, p = 0.045. Separate analysis of the damage to the hands and feet suggests that this difference in rate of increase of damage is more pronounced in the joints of the feet than in the hands. The rate of damage was independently associated with less disease activity, less frequent use of glucocorticoids, and with an improvement in aerobic fitness. CONCLUSION: The progression of radiological joint damage of the hands and feet in patients with RA is not increased by long term high intensity weightbearing exercises. These exercises may have a protective effect on the joints of the feet.     

Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis in response to disease-modifying antirheumatic drug treatment and correlation with radiologic outcome

OBJECTIVE: To demonstrate the effect of treatment with disease-modifying agents on the expression of osteoprotegerin (OPG) and RANKL in the synovial tissue from rheumatoid arthritis (RA) patients and to correlate these changes with radiologic damage measured on sequential radiographs of the hands and feet. METHODS: Synovial biopsy specimens were obtained at arthroscopy from 25 patients with active RA (16 of whom had a disease duration <12 months) before and at 3-6-month intervals after starting treatment with a disease-modifying agent. Immunohistologic analysis was performed using monoclonal antibodies to detect OPG and RANKL expression, with staining quantitated using computer-assisted image analysis and semiquantitative analysis techniques. Serial radiographs of the hands and feet were analyzed independently by 2 radiologists and a rheumatologist using the van der Heide modification of the Sharp scoring method. RESULTS: Thirteen patients achieved a low disease state as defined by a disease activity score <2.6 while 19 patients achieved an American College of Rheumatology response >20% after disease-modifying antirheumatic drug (DMARD) treatment. Successful DMARD treatment resulted in an increase in OPG expression and a decrease in RANKL expression at the synovial tissue level, which correlated with a reduction in erosion scores measured on annual radiographs of the hands and feet. CONCLUSION: Successful treatment-induced modulation of OPG and RANKL expression at the synovial tissue level, resulting in a reduction in the RANKL:OPG ratio, is likely to have a significant impact on osteoclast formation and joint damage in patients with active RA.     

Power Doppler ultrasonographic monitoring of response to anti-tumor necrosis factor therapy in patients with rheumatoid arthritis

OBJECTIVE: To evaluate the validity, responsiveness, and predictive value of power Doppler ultrasonography (PDUS) monitoring of response to tumor necrosis factor (TNF) blocking agents in rheumatoid arthritis (RA). METHODS: Three hundred sixty-seven RA patients were prospectively recruited at 25 Spanish centers; complete clinical, laboratory, and PDUS data were obtained on 278 patients. The patients underwent clinical, laboratory, and PDUS assessment at baseline and after 1, 3, 6, and 12 months of anti-TNF treatment, and radiographic assessment of the hands and feet at baseline and 12 months. The Disease Activity Score in 28 joints (DAS28) was recorded at each visit. PDUS examination included 86 intraarticular and periarticular sites in 28 joints. US synovial fluid (SF), synovial hypertrophy (SH), and PD signal were scored in all synovial sites. US count and index for SF, SH, and PD signal were obtained. Sensitivity to change of the PDUS variables was assessed by estimating the smallest detectable difference (SDD) from the intraobserver variability. RESULTS: A significant parallel improvement in DAS28 and PDUS parameters was found at followup assessment (P < 0.0005 for within-subject between-visit changes). The SDD for PDUS parameters was lower than the mean changes throughout followup. Time-integrated values of US joint count for PD signal and rheumatoid factor (RF) showed predictive value in relation to progression of radiographic erosion (R = 0.64), and time-integrated values of US joint count for PD signal, RF, and erythrocyte sedimentation rate were predictors of progression of the total radiographic score (R = 0.59). CONCLUSION: These findings indicate that PDUS is a valid method for monitoring response to anti-TNF therapy in RA; results obtained by PDUS are reproducible and sensitive to change. PDUS findings may have predictive value in relation to radiologic outcome.     

Comparison of disability and quality of life in rheumatoid and psoriatic arthritis

OBJECTIVE: There is controversy about the severity of peripheral psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA). Early reports found PsA to be a milder disorder, excepting the mutilans form. Recent reports suggest that PsA can be as severe as RA. We compared severity, disability, and quality of life in patients with PsA and RA matched primarily for disease duration. METHODS: Data relating to the extent and severity of disease were recorded in a hospital clinic setting. Recent radiographs of hands and feet were read blinded to diagnosis, and information on function and quality of life was collected with the Health Assessment Questionnaire (HAQ) and EuroQol-5D, respectively. RESULTS: Forty-seven patients were matched for disease duration (median PsA 5 yrs, RA 7 yrs). The male/female ratio was 24/23 for PsA, 16/31 for RA, and median ages were 45 and 51 years, respectively. Patients with RA had significantly more joint involvement of metacarpophalangeal joints and wrists, whereas distal interphalangeal joints, spine, sternoclavicular joints, and sacroiliac joints were significantly more involved in PsA. No difference was found regarding Ritchie Articular Index, inflammatory markers, HAQ score, or EuroQol-5D. Patients with RA had significantly more damage on radiographs of hands and feet: median (range) Larsen score hands PsA 8 (0-91), RA 38 (0-125); feet PsA 4 (0-34), RA 11(0-56). Patients with RA were taking significantly more disease modifying drugs. CONCLUSION: Peripheral joint damage is significantly greater in RA than in PsA after equivalent disease duration, but function and quality of life scores are the same for both groups. The additional burden of skin disease in PsA may account for this.     

Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting

OBJECTIVE: To analyse the frequency and prognostic factors of radiographic progression in a series of Spanish patients with early rheumatoid arthritis (RA) after 1 yr of treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Sixty patients (47 females, 13 males) with RA with a disease duration shorter than 2 yr [mean (s.d.) duration 9.5+/-6.6 months] were treated with the same therapeutic protocol using gold salts as the first DMARD and methotrexate as a second option, and were followed up for 1 yr. Radiographic progression in the hands and feet (total radiographic Larsen score and the erosion joint count) was used as the outcome variable. Clinical, laboratory, immunogenetic and radiographic data were obtained at study entry. Disease activity and response to therapy were measured at 6 and 12 months. RESULTS: Erosive disease was found in 21.7% of patients at baseline and in 38.3% after 1 yr. Although a substantial reduction in disease activity was observed during the 1 yr follow-up [disease activity score (DAS28) 5.8+/-0.8 at entry and 3.9+/-1.3 at 12 months, P < 0.001], the Larsen score rose from 1.9+/-3.3 to 5.6+/-9.8 after 1 yr. In 26.6% of patients, a raised erosion joint count was observed after 1 yr. Radiographic progression in the total joint radiographic damage (increase in Larsen score of >or=2) was observed in 36.6%. In the multivariate analysis, baseline pain [visual analogue scale (VAS)] and the presence of two copies of the shared epitope were associated with radiographic progression in the erosion joint count. Disease duration before study entry, VAS pain and Larsen score at baseline were significant predictors of radiographic progression in total damage (Larsen score). Baseline radiographic damage had the highest positive predictive value for progression. CONCLUSIONS: Radiographic progression was observed in up to 36.6% of patients with early RA after 1 yr of DMARD therapy in spite of a significant reduction in disease activity. Baseline factors, such as VAS pain, disease duration until DMARD therapy, damage score at baseline and the presence of two copies of the shared epitope, were associated with radiographic progression.     

A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience

OBJECTIVE: To determine the clinical presentation and clinical and radiological outcome of early psoriatic arthritis (PsA) at 1 and 2 yr. METHODS: Patients with PsA were assessed at the St. Vincent's University Hospital Early Synovitis Clinic. Standardized clinical and laboratory assessment was performed at presentation and 1- and 2-yr follow-up. Radiographs of the hands and feet were evaluated in chronological order by two trained observers using the Sharp method modified to include the distal interphalangeal (DIP) joints. RESULTS: A total of 129 (12.7%) of 1018 patients were diagnosed with PsA [mean age at onset of arthritis was 40.4 yr (range 11-76); mean duration of disease was 9.9 months (range 0.3-48); 52 oligoarticular, 77 polyarticular]. Means and standard deviations of indices of disease activity at presentation were: 10-cm visual analogue scale = 4.8 +/- 2.7, HAQ score = 0.71 +/- 0.64, ACR functional class III/IV = 41 (35%), Ritchie Articular Index = 5.6 +/- 6, swollen joint count = 6.9 +/- 8, erythrocyte sedimentation rate = 24 +/- 26.4 mm/h, C-reactive protein = 27.6 +/- 58.5 mg/l. At presentation, 49 (38%) patients had peripheral enthesopathy, 13 patients (10%) had inflammatory spine pain and 50 (39%) patients had DIP involvement. A total of 119 had psoriasis at the time of presentation [plaque psoriasis in 112 (94%), mean age of psoriasis onset was 29.8 +/- 16.2 yr, nail dystrophy present in 78 patients (67%)]. At 1 yr of follow-up, 119 (92%) patients were reassessed and 70 (59%) were taking a disease-modifying anti-rheumatic drug (DMARD). At 2 yr, 97 (75%) patients were reassessed and 54 (56%) were taking a DMARD. Despite considerable improvement in inflammation and function scores, only 31 (26%) patients were in remission at 1 yr with 20 (21%) in remission at 2 yr. There was a low rate of DMARD-free remission [14 (12%) at 1 yr and 11 (11%) at 2 yr]. Radiographs of hands and feet were obtained for 117 (91%) patients at presentation and 86 (67%) patients at a median follow-up of 24 months (range 11-56); 47% of patients had joint erosions in hands or feet at follow-up with a mean Sharp erosion score of 3 (0) +/- 5.2 (range 0-25) and a mean Sharp narrowing score of 3.2 (0) +/- 7.5 (range 0-48). CONCLUSION: This study confirms that PsA is a chronic, progressive disease in the majority of patients. Despite clinical improvement with current DMARD treatment, PsA results in radiological damage in up to 47% of patients at a median interval of 2 yr.     

Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression

OBJECTIVE: To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS: In a 3 year prospective study of 33 patients with early RA (symptoms < 1 year at entry) monthly measurements of serum MMP-3 were transformed into time integrated values for 6 month periods for comparison with other markers of disease activity like swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), the disease activity score (DAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and radiological progression, scored according to Sharp's method, in which erosions and joint space narrowing are scored separately and combined to a total Sharp score. RESULTS: Significant correlations were found between serum MMP-3 and SJC, ESR, and CRP during all periods and between 6 and 30 months with the DAS. There were no correlations between serum MMP-3 and TJC or the RAI. During the first 12 months serum MMP-3 was correlated only with the item joint space narrowing of the Sharp score. After 12 months of followup it was also correlated with the total Sharp score and after 18 months it was correlated with all 3 items of the Sharp score. There was a wide interindividual variation in the relation between serum MMP-3 and radiological progression but intraindividually this relation seemed to be rather constant. CONCLUSION: Time integrated values of serum MMP-3 are correlated with time integrated values of other markers of disease activity such as joint swelling, ESR, CRP, and the DAS. Of the radiological scores, as outcome measures, especially joint space narrowing correlated closely with cumulative serum MMP-3.