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Objective: With modern initial aggressive combination treatments with synthetic disease-modifying antirheumatic drugs (sDMARD), most patients with rheumatoid arthritis (RA) achieve remission, have marginal radiographic progression, and sustain normal function. Here we aim to identify the patients failing these targets even after aggressive treatment., Methods: Ninety-nine patients with early, active RA were treated with a combination of 3 sDMARD and prednisolone (PRD), and either infliximab or placebo infusions during the first 6 months, aiming at strict remission. After 24 months, the treatments became unrestricted. At 60 months, 4 evident clinical features of treatment failure were defined: area under curve (AUC) between 6-60 months for disease activity score assessing 28 joints > 2.6; AUC 6-60 for health assessment questionnaire > 0.5; progression in total Sharp/van der Heijde score 0-60 months > 3 units; and need of PRD or biologic DMARD treatment at 60 months., Results: A total of 93 patients were followed up for 60 months. Of them, 45 had no features of treatment failure, 30 had 1, 10 had 2, 7 had 3, and 1 patient had all 4 features. Having 2-4 features of treatment failure at 5 years was predicted by the health assessment score at baseline, and by even low residual disease activity at 3 and 6 months., Conclusions: Only 20% of the patients with RA treated early with combination sDMARD and PRD have more than 1 clinical feature of treatment failure at 60 months. Residual clinical disease activity at 3-6 months was the most important predictor for identifying these patients. The study was registered at www.clintrials.gov (NCT00908089).

Objective: Randomized controlled studies have demonstrated protective advantages of biologic therapies over the synthetic disease-modifying antirheumatic drugs (DMARD) in slowing joint damage progression in patients with rheumatoid arthritis (RA). This effect appears to be largely independent of the clinical disease control. We measured the rate of radiographic progression in patients with RA in clinical remission treated with synthetic versus biologic DMARD., Methods: This is an observational cohort study of patients with RA in clinical remission, nested within the Swiss Clinical Quality Management in Rheumatoid Arthritis (SCQM-RA) Registry. The primary study outcome was the rate of radiographic progression (Ratingen erosion score), and a secondary outcome was functional disability [Health Assessment Questionnaire-Disability Index (HAQ-DI)] progression. We compared the rate of progression between synthetic and biologic DMARD using a multivariate regression model for longitudinal data, adjusting for potential confounders., Results: A total of 2055 patients in the SCQM-RA registry were in remission at least once from 1999 to 2012 and met the study inclusion criteria. Baseline characteristics of patients in remission receiving synthetic and biologic DMARD were not significantly different in terms of prognostic factors for joint damage progression. During followup, erosion progression differed significantly between the 2 groups [1.4% (95% CI: 1.1-1.6) vs 0.9% (95% CI: 0.5-1.2) of progression over 3 years, respectively, p < 0.001], with less damage progression in patients treated with biologic DMARD than with synthetic DMARD. This difference remained significant after adjusting for confounding factors. The evolution of the HAQ-DI score was also statistically better in the biologic group (p < 0.001)., Conclusion: This observational study confirms that the rate of structural damage progression in clinical remission is decreased taking biologics compared to synthetic DMARD. However, while the difference is statistically significant it is probably not relevant from a clinical perspective.

Objective: To compare the initial clinical, biological, and radiographic findings of early arthritis by positivity for rheumatoid factor (RF) and/or anticyclic citrullinated peptide antibodies (anti-CCP), and to validate a patient profile based on this serologic information., Methods: The ESPOIR cohort comprises patients presenting synovitis of at least 2 joints for 6 weeks to 6 months. Patients underwent testing for IgM rheumatoid factor (IgM-RF) and anti-CCP2 antibodies and were divided into 4 groups: RF- and anti-CCP- (group 1), RF+ and anti-CCP- (group 2), RF- and anti-CCP+ (group 3), RF+ and anti-CCP+ (group 4). We compared the groups in terms of clinical, biological, and radiographic features (baseline scores and 6-month and 12-month progression)., Results: Of the 813 recruited patients, 406 (50%) were in group 1, 91 (11.2%) in group 2, 34 (4.1%) in group 3, and 281 (34.6%) in group 4. Mean baseline erythrocyte sedimentation rate and C-reactive protein were higher for anti-CCP+ groups (groups 3 and 4) than for other groups (p < 0.001), and van der Heijde-modified Sharp score for radiographs was higher for group 4 than for other groups (p < 0.001). Clinical presentation was not consistently associated with serologic profile. Radiographic progression at 1 year was higher for anti-CCP+ groups than other groups (p < 0.001)., Conclusion: The phenotype of patients with early arthritis with or without anti-CCP and/or RF positivity did not correspond to a particular clinical presentation. However, baseline acute-phase reactants and short-term radiographic progression were high in patients with anti-CCP positivity, which may be associated with the inflammatory process and progressive disease in patients with early arthritis.

Objective: Factors relevant to the discordance between the patient global assessment (PGA) and estimator global assessment (EGA) in patients newly diagnosed with rheumatoid arthritis (RA) were examined., Methods: Seventy-five consecutive newly diagnosed patients with RA were prospectively enrolled. We used 3 models in which discordance between PGA and EGA at 12 months was set at 5 mm, 10 mm, or 20 mm. We adopted 10 mm as representative and examined time course changes in clinical variables over 12 months., Results: No significant difference was found between the concordance and the higher PGA groups regarding baseline characteristics and treatment. At 12 months, EGA, swollen joint count, and inflammatory marker values were not different, but pain visual analog scale and tender joint count were significantly higher in the higher PGA group, and the Health Assessment Questionnaire improved less. In the 10 mm and 20 mm models, the structural remission rate was significantly lower in the higher PGA group and the rapid radiological progression rate significantly higher. The discrepancy was already significant at 3 months., Conclusion: In newly diagnosed RA, PGA at 12 months may be more sensitive for indicating progressive joint destruction and functional impairment when compared with EGA, and there is a discrepancy directed toward a worse assessment by patients.

Objective: To report the 5-year outcome of a large prospective cohort of patients with very early rheumatoid arthritis (RA), and to identify factors predictive of outcome., Methods: Patients were recruited if they had early arthritis of < 6 months' duration, had a high probability of developing RA, and had never been prescribed disease-modifying antirheumatic drugs (DMARD) or steroids. Logistic regression analysis was used to determine factors that predict outcome., Results: We included 813 patients from December 2002 to April 2005. Age was 48.1 ± 12.6 years, delay before referral 103.1 ± 52.4 days, 28-joint Disease Activity Score (DAS28) 5.1 ± 1.3, Health Assessment Questionnaire (HAQ) 1.0 ± 0.7; 45.8% and 38.7% had rheumatoid factor or antibodies to cyclic citrullinated peptide (anti-CCP), respectively; 22% had hand or foot erosions; 78.5% fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8% during followup. At 5 years, 573 patients were evaluated. The outcome was mild for most patients: disease activity (median DAS28 = 2.5) and HAQ disability (median 0.3) were well controlled over time; 50.6% achieved DAS28 remission and 64.7% low disease activity. Radiographic progression was low (2.9 Sharp unit/year) and only a few patients required joint surgery. Nevertheless, some patients developed new comorbidities. During the 5 years, 82.7% of patients had received at least 1 DMARD (methotrexate, 65.9%), 18.3% a biological DMARD, and about 60% prednisone at least once. Anti-CCP was the best predictor of remaining in the cohort for 5 years, of prescription of synthetic or biologic DMARD, and of radiographic progression., Conclusion: The 5-year outcome of an early RA cohort in the 2000s was described. Anti-CCP was a robust predictor of outcome. The generally good 5-year outcome could be related to early referral and early effective treatment, key processes in the management of early RA in daily practice.

Objective: To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy., Methods: Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28., Results: In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28., Conclusion: In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

Objective: To determine the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in patients with psoriatic arthritis (PsA) and to identify the features associated with its occurrence., Methods: Patients were recruited from the University of Toronto PsA observational cohort initiated in 1978. All patients fulfilled the CASPAR criteria. Radiographs of peripheral joints and spine were obtained every 2 years. DISH was defined as flowing bony bridges in at least 4 contiguous thoracic vertebrae. Each PsA patient with DISH was matched by sex to 3 PsA patients without DISH. Demographics, disease characteristics, and radiographic features were compared using McNemar test, Fisher's exact test, chi-square test, and paired t test as appropriate. Logistic regression analyses models with stepwise regression were conducted., Results: DISH was observed in 78 (8.3%) of 938 patients with PsA. Patients with DISH were older and had longer disease duration, higher body mass index (BMI), and higher uric acid levels. Diabetes and hypertension were more prevalent in patients with DISH than in those without. The severity of radiographic damage to peripheral joints was also greater in patients with DISH. The presence of inflammatory back pain, HLA-B*27 allele, and sacroiliitis was similar in both groups. Patients with DISH had more syndesmophytes and calcaneal spurs. Older age, higher BMI, and the presence of radiographic damage to peripheral joints were associated with DISH in multivariate analysis., Conclusion: The diagnosis of DISH is possible in the presence of axial PsA. DISH was associated with known DISH-related factors including older age and high BMI, as well as the presence of radiographic damage to peripheral joints.

Objective: Clinical remission currently is the treatment target for all patients with rheumatoid arthritis (RA). At the same level of inflammation, the prognosis regarding joint damage is believed to be different for anticitrullinated protein antibody (ACPA)-negative and ACPA-positive patients. Our objective was to show the difference in prognosis at similar disease activity levels, and to illustrate how this could be translated to differentiation of treatment targets., Methods: Data were used from the Nijmegen Early RA Cohort. The relation between the time-averaged disease activity level (by Disease Activity Score; DAS) and joint damage progression over 3 years was analyzed, separately for ACPA-negative and ACPA-positive patients. Joint damage was assessed as change in Ratingen score, and dichotomized as occurrence of erosions in joints that were unaffected at baseline. Linear and logistic multivariable regression models were used., Results: The regression coefficient of DAS on change in Ratingen score was 3.9 (p < 0.001) for ACPA-negative and 4.7 (p < 0.001) for ACPA-positive patients, showing less joint damage progression at the same disease activity level in ACPA-negative patients. This difference became greater with increasing disease activity. The probability for erosions in joints unaffected at baseline was 0.35 in ACPA-negative patients when time-averaged DAS was < 2.4 versus 0.80 in ACPA-positive patients., Conclusion: At the same level of inflammation, ACPA-negative patients have less joint damage and lower probability for damage in newly affected joints than ACPA-positive patients. Low disease activity might be a sufficiently strict treatment target for ACPA-negative patients to prevent progression of joint damage.

Objective: Radiographic damage was recently identified as a feature of poor prognosis in polyarticular juvenile idiopathic arthritis (pJIA). However, most radiographic studies did not differentiate pJIA from other subtypes of JIA and little is known about pJIA persisting into adulthood. We describe radiological peripheral involvement in young adults with pJIA compared to patients with rheumatoid arthritis (RA)., Methods: All consecutive patients with pJIA followed in a transition program were included. Age, sex, disease duration, and medical or surgical treatment information was collected. Laboratory tests and standard radiographs of the hands and wrists, feet, and hips were analyzed by 2 independent radiologists blinded to the diagnosis. One RA control group (age < 55 yrs), matched for sex and disease duration, was recruited., Results: Forty-three patients with pJIA and 59 with RA were included. Radiographs showed hand lesions in 79% of pJIA and 86% of patients with RA, feet lesions in 74% of pJIA and 80% of patients with RA, and hip damage in 35% of pJIA and 17% of patients with RA (p = nonsignificant). Specific to the juvenile forms were lower frequency of proximal interphalangeal joint involvement (51% vs 76%; p = 0.03) and higher risk of bilateral hip damage (86% vs 25%; p < 0.01) than in adult RA., Conclusion: Structural peripheral damage is as common and as severe in young adults with pJIA as in adults with RA. The main specific feature of pJIA seems to be a high risk of bilateral hip damage. This requires a particular monitoring of pJIA patients with unilateral hip involvement to detect bilateralization.

Objective: To compare the performance of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria with the 1987 American Rheumatism Association (ARA) criteria for rheumatoid arthritis (RA) in an early arthritis cohort., Methods: The study included 79 patients with early arthritis (symptoms < 12 months) and a minimum of 1 year of followup between January 2004 and August 2010. Case notes were reviewed to determine which criteria were fulfilled at initial, 3-month, 1-year, and 2-year visits. Requirements for disease-modifying antirheumatic drug (DMARD) therapy and presence of joint erosions were compared at 2 years., Results: At the initial visit, twice as many patients fulfilled the 2010 criteria (67%) compared with the 1987 criteria (34%; p < 0.001). Forty-four percent of patients who fulfilled only the 2010 criteria at the initial visit went on to fulfill both 1987 and 2010 criteria at 3 months (p < 0.001). Eight patients did not meet the 1987 RA criteria solely because of short symptom duration. All 17/79 patients who developed joint erosions went on to eventually fulfill both criteria. Of those patients who fulfilled only the 2010 criteria at baseline, 25/27 (93%) ultimately received DMARD therapy compared with 24/26 (92%) of those fulfilling both 1987 and 2010 criteria., Conclusion: The 2010 ACR/EULAR RA criteria allowed earlier RA classification compared to the 1987 ARA criteria, although both criteria were equivalent in predicting joint erosions and subsequent need for DMARD (Australian New Zealand Clinical Trials Registry ANZCTR 12608000292370).

Objective: To evaluate the efficacy and safety of initial combination treatment with adalimumab (ADA) and methotrexate (MTX) versus monotherapy with ADA or MTX during an open-label extension of PREMIER., Methods: Patients with early rheumatoid arthritis (RA) received blinded ADA plus MTX, ADA alone, or MTX alone for 2 years in PREMIER. At Year 2, patients could enroll in an open-label extension and receive ADA monotherapy; MTX could be added at the investigator's discretion. Longterm efficacy results are presented as observed data., Results: In the open-label period, 497 of the original 799 randomized patients had ≥ 1 dose of ADA (by original randomization: ADA plus MTX, n = 183; ADA, n = 159; MTX, n = 155). In the completers cohort [patients with available Year-5 ACR responses and modified total Sharp scores (mTSS)], the Year-5 mean change from baseline in mTSS for the ADA+MTX arm (n = 124) was 2.9, compared with 8.7 and 9.7 in the ADA (n = 115) and MTX (n = 115) arms. Comprehensive disease remission, defined as the combination of DAS28 remission, normal function (Health Assessment Questionnaire ≤ 0.5), and radiographic nonprogression (ΔmTSS ≤ 0.5), was achieved by more patients in the initial ADA+MTX arm (35%) than in the ADA (13%) or MTX (14%) arms., Conclusion: Initial combination treatment with ADA plus MTX, followed by open-label ADA, led to better longterm clinical, functional, and radiographic outcomes than either initial ADA or MTX monotherapy during 5 years of treatment.

Objective: To quantify the association of radiographic osteoarthritis (ROA) in one knee or hip joint with other knee or hip joints., Methods: We analyzed baseline data from the Johnston County Osteoarthritis Project (n = 3068). We fit 4 models for left/right knee/hip. The Kellgren-Lawrence (KL) radiographic grade severity scale was KL 0/1 (no/questionable ROA), 2 (mild ROA), or 3/4 (moderate/severe ROA). We estimated associations between KL grade in contralateral joints and other joint sites (e.g., worst hip in knee models), adjusting for sex, race/ethnicity (African American/white), age, and measured body mass index, using cumulative odds logistic regression models. Interactions were investigated: race/ethnicity by sex; race/ethnicity and sex by the 2 explanatory variables., Results: Contralateral joint KL grade was strongly associated with KL grade, with OR ranging from 9.2 (95% CI 7.1, 11.9) to 225.0 (95% CI 83.6, 605.7). In the left knee model, the contralateral joint association was stronger among African Americans than whites, but for the other models the associations by race/ethnicity were identical. Models examining other joint sites showed weaker but mostly statistically significant associations (OR 1.4 to 1.8)., Conclusion: We found a strong multivariable-adjusted association between KL grades in contralateral knees and hips, and a modest association with the other joint site (e.g., knees vs hips). These results suggest that diagnosis of ROA in 1 large joint may be a marker for risk of multijoint ROA, and warrant interventions to reduce the incidence or severity of ROA at these other joints.

Objective: Toll-like receptors (TLR) have been implicated in the pathogenesis of arthritis. We investigated the role of functional variants of TLR in the disease phenotype and severity of rheumatoid arthritis (RA)., Methods: All patients from a longterm observational inception cohort (n = 319) were genotyped for 22 single-nucleotide polymorphisms (SNP) in TLR2, 3, 4, 5, 7, 8, and 9 using multiplex assays. Clinical characteristics including sex, age at disease onset, rheumatoid factor (RF), and shared epitope positivity and disease activity score and radiological progression were taken into account. Genotypes were analyzed for association with Disease Activity Scores (DAS28) and joint damage (Rau scores) at 3 and 6 years., Results: After Bonferroni correction, there was a moderate association between RF positivity and TLR8-rs5741883. No other TLR variant was significantly associated with any RA clinical characteristics., Conclusion: Using a large inception cohort and strict statistical evaluation, we could not identify an association between functional TLR variants and RA phenotype and disease severity. This suggests the functional TLR variants do not play a major role in RA phenotype and disease severity.

Objective: Axial involvement is an important manifestation of psoriatic arthritis (PsA). We aimed to identify risk factors associated with the presence of axial PsA (AxPsA) in patients with PsA., Methods: Patients with AxPsA (bilateral sacroiliitis >or= grade 2/unilateral sacroiliitis >or= 3 and inflammatory neck/back pain or limited spinal mobility) at first clinic visit were identified from the University of Toronto PsA clinic database. Risk factors associated with the presence of AxPsA were determined. Subsequently, patients without AxPsA at first clinic visit were identified. Under a multistate framework, the proportion of patients with PsA who subsequently developed AxPsA was estimated robustly using marginal methods and a Markov model. Risk factors at baseline that were associated with future development of AxPsA were identified through multiplicative time-homogeneous Markov models., Results: Our study included 206 patients. Fifty patients had AxPsA at first clinic visit. HLA-B*27, radiographic damage to peripheral joints, and elevated erythrocyte sedimentation rate (ESR) increased odds of having AxPsA, while family history of PsA decreased the odds. One hundred fifty-six patients did not have AxPsA at first clinic visit. On followup, 28 developed AxPsA, and 11 died. We estimated that after 10 years of followup, 15% would develop AxPsA. Nail dystrophy, number of radiographically damaged joints, periostitis, and elevated ESR increased the risk of developing AxPsA, while swollen joints decreased the risk., Conclusion: These results suggest that severe peripheral arthritis and HLA-B*27 are risk factors for AxPsA.

Objective: To determine the relationship between radiographic progression and clinical response for adalimumab plus methotrexate (MTX) versus either monotherapy in patients with early rheumatoid arthritis (RA) in the PREMIER study., Methods: Patients with early RA who received adalimumab plus MTX (n = 240), adalimumab (n = 222), or MTX (n = 216) were grouped by American College of Rheumatology (ACR) response, 28-joint Disease Activity Score (DAS28), or remission-like state [tender joint count (TJC) = 0; DAS28 < 2.6; swollen joint count = 0; ACR100] at 26 and 104 weeks. Radiographic progression was assessed by cumulative probability plots, mean changes in total Sharp score (DeltaTSS), and percentages of progressors (DeltaTSS > 0.5)., Results: Across the spectrum of clinical outcomes, including ACR20 nonresponses and remission-like responses, therapy with adalimumab plus MTX permitted less radiographic progression at Weeks 26 and 104 than MTX monotherapy. Adalimumab monotherapy was generally intermediate. A strong, proportional relationship was observed between clinical response and radiographic efficacy only for MTX monotherapy. The monotherapies approximated the radiographic efficacy of adalimumab plus MTX only among remission-like responders, although progression was significantly greater with MTX monotherapy versus adalimumab plus MTX for patients with TJC = 0. Concurrent clinical (DAS28 < 2.6) and radiographic (DeltaTSS

Objective: To study the value of HLA-DRB1 shared epitope (SE), -308 tumor necrosis factor-alpha (TNF-alpha) gene promoter polymorphism, rheumatoid factor (RF), anti-citrullinated peptide antibodies (anti-CCP), and baseline erosions for predicting radiological outcome at 1 year in patients with recent-onset rheumatoid arthritis (RA)., Methods: Radiological damage was assessed by radiographs at baseline and at 1 year in an inception cohort of 134 RA patients with disease duration

Objective: We previously demonstrated that levels of fibrin d-dimer correlate with disease activity and response to therapies in systemic juvenile idiopathic arthritis (sJIA). We hypothesized that persistence of D-dimer elevation in the patterns previously described, but over a longer followup period, would signal poor outcome., Methods: We studied 31 children identified from 2 centers. Subjects were assigned a risk category based on their first obtained D-dimer concentration. Risk categories were based on results of our initial study, where normalization of D-dimer in patients no longer taking immunosuppressive therapy predicted good short-term outcome, and persistent D-dimer elevation while taking immunosuppressives predicted bad outcome (radiographic abnormalities, joint replacement surgery, or poor functional class) or a severe systemic manifestation. Outcome was determined at the last followup visit, a minimum of 2 years after measurement of the initial d-dimer level., Results: The 31 children were a mean 16.4 years old at an average of 8.8 years after their initial diagnosis. Ten children had a severe outcome during this period; all 10 had a study baseline risk category of "high." Of the 14 subjects who had a high risk category at study baseline, none had a mild outcome., Conclusion: Our study indicated that a paradigm of risk of severe disease based upon persistent elevation of fibrin d-dimer on first measurements (greater than a mean of 29 months in our initial study and at least 24 months in the additional subjects) is promising to predict poor longer-term outcome in sJIA. A larger prospective study is warranted to substantiate the preliminary data and assess the relative comparative value to other biomarkers and clinical endpoints.

Objective: To determine time trends in incidence, prevalence, and clinical characteristics of psoriatic arthritis (PsA) over a 30-year period., Methods: We identified a population-based incidence cohort of subjects aged 18 years or over who fulfilled ClASsification of Psoriatic ARthritis (CASPAR) criteria for PsA between January 1, 1970, and December 31, 1999, in Olmsted County, Minnesota, USA. PsA incidence date was defined as the diagnosis date of those who fulfilled CASPAR criteria. Age- and sex-specific incidence rates were estimated and age- and sex-adjusted to the 2000 US White population., Results: The PsA incidence cohort comprised 147 adult subjects with a mean age of 42.7 years, and 61% were men. The overall age- and sex-adjusted annual incidence of PsA per 100,000 was 7.2 [95% confidence interval (CI) 6.0, 8.4] with a higher incidence in men (9.1, 95% CI 7.1, 11.0) than women (5.4, 95% CI 4.0, 6.9). The age- and sex-adjusted incidence of PsA per 100,000 increased from 3.6 (95% CI 2.0, 5.2) between 1970 and 1979 to 9.8 (95% CI 7.7, 11.9) between 1990 and 2000 (p for trend < 0.001). The point prevalence per 100,000 was 158 (95% CI 132, 185) in 2000, with a higher prevalence in men (193, 95% CI 150, 237) than women (127, 95% CI 94, 160). At incidence, most PsA subjects had oligoarticular involvement (49%) with enthesopathy (29%)., Conclusion: The incidence of PsA has been rising over 30 years in men and women. Reasons for the increase are unknown, but may be related to a true change in incidence or greater physician awareness of the diagnosis.

Objective: To evaluate the 5-year incidence of cervical spine disorders in patients with early rheumatoid arthritis (RA) treated by 2 different disease modifying antirheumatic drug (DMARD) strategies., Methods: In a national, multicenter, prospective FIN-RACo-trial, a cohort of 199 patients with early, clinically active RA was randomly assigned to treatment with a combination of 3 DMARD and prednisolone (Combi group) or with a single DMARD (Single group) with or without prednisolone, aiming to induce remission. After 2 years, the DMARD therapy was unrestricted. Lateral view cervical spine radiographs during full flexion and extension were taken at the 5-year followup visits. The presence of anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI), and subaxial subluxation (SAS) was assessed in the 149 patients with radiographs available (80 Single and 69 Combi)., Results: At the 5-year visits, aAAS, AAI, and SAS were found in 13 (9%), 6 (4%), and 9 (6%) patients, respectively. The corresponding Single/Combi group ratios were 11/2, 5/1, and 5/4. Of the baseline data, only poor physical function [Health Assessment Questionnaire (HAQ); p = 0.024] and Single treatment strategy (p = 0.019) were significantly associated with aAAS. Worse HAQ scores and Disease Activity Score 28 values were found in patients who developed aAAS during the 5-year followup., Conclusion: RA patients with sustained clinical disease activity and poor HAQ are at increased risk of developing aAAS. The development of aAAS during the first 5 years of RA was rare among the patients treated with a combination of DMARD for at least 2 years from the diagnosis. Intensive treatment with traditional DMARD prevents or retards the development of aAAS in patients with recent-onset RA.

Objective: Comparison of performances of 5 (semi)automated methods in measuring joint space width (JSW) in rheumatoid arthritis., Methods: Change in JSW was determined by 5 measurement methods on 4 radiographs per patient from 107 patients included in the COBRA trial (comparing sulfasalazine alone or in combination with methotrexate and corticosteroids). For each method the number of patients with sufficient available results was assessed (efficiency). An independent repeated measurement was carried out on a random sample of 30 patients' baseline and 1-year radiographs, to evaluate within-method reliability of change scores. Discriminatory ability (DA) of the measurement methods (between the 2 treatment arms) was compared with the DA of the Sharp-van der Heijde score (SHS) and its 2 components (erosion and JSW scores)., Results: The overall success rate varied widely between methods. Applying the chosen threshold of a minimum of 50% available joints with a change score per patient resulted in a success rate > 92% in 4/5 methods. Repeatability of measurements was good for most methods (intraclass correlation coefficient > or = 0.80 in 4/5 methods). Almost all measurement methods in 3 followup periods (12/14) showed a lower mean loss of JSW in patients from the intensive treatment group, although this was rarely statistically significant, confirming the known difference in structural damage. JSW as measured by the (semi)automated systems often showed higher DA than the JSW score of the SHS, but was lower than the total SHS and erosion scores., Conclusion: Although efficiency of the methods should be improved further, results already show good reliability and encouraging DA of most methods. Optimal information may be obtained with a combination of scoring of erosions and (semi)automated measurement of JSW.

Objective: To identify the optimal combination for detecting erosions in early rheumatoid arthritis using extremity magnetic resonance imaging (eMRI)., Methods: In 44 patients, eMRI of 1 hand identified 77% who were erosive, 2 hands 89%, and 2 hands and feet 91%., Results: eMRI identified 4 times as many erosions as radiography. At 6 months, eMRI of 1 hand identified an increase in erosions in 50% subjects, 2 hands in 55%, and 2 hands and feet in 55%. When only subjects with a change in erosion score above the smallest detectable difference were considered, these numbers were 30%, 25%, and 20%, respectively., Conclusion: eMRI provides superior erosion identification compared to radiography. Imaging 2 hands can be used as a screening tool and 1 hand to monitor erosions over time.

Repair of structural damage in rheumatoid arthritis has drawn much attention with newly available effective treatments. A workshop was held at OMERACT 8 to update current knowledge on the validity of the concept of repair and on the assessment of repair. In preparation for the workshop several studies were performed and the results were presented. This was followed by a discussion and voting on statements on various aspects of repair. A majority of participants agreed that results of the new studies strengthen the validity of the concept of repair, and that repair can be assessed on radiographs. There was less agreement on the best means of measurement and there was a plea for more extensive reporting of data, i.e., not limited to sum scores of all joints together. The conclusions of the workshop mean a big step forward in the acceptance and assessment of repair.

Objective: To study sustainability of remission and good treatment response, and the association of both with radiographic progression, in early rheumatoid arthritis (RA) in the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN-RACo)., Methods: Patients were randomized to receive either a combination of disease modifying antirheumatic drugs (DMARD; COMBI, n = 97) or a single DMARD (SINGLE, n = 98). Remission was defined according to modified American College of Rheumatology (ACR) remission criteria and Disease Activity Score 28 joint count (DAS28) < or = 2.6, and sustained remission as presence of remission at 6, 12, and 24 months. Good treatment response was defined as DAS28 (3/4) 3.2 and decrease of DAS28 >1.2., Results: In 169 patients with complete data, 33 (42%) COMBI and 18 (20%) SINGLE patients achieved modified ACR remission at 2 years, which was sustained in 11 (14%) COMBI and 3 (3%) SINGLE patients. Fifty-four (68%) COMBI and 37 (41%) SINGLE patients were in DAS28 remission at 2 years, which was sustained in 40 (51%) COMBI and 14 (16%) SINGLE patients. Good treatment response was sustained in 67% of COMBI and 27% of SINGLE patients. Over 2 years, the Larsen score increased by a median of 1 (95% CI 0-2) in patients in sustained DAS28 remission compared to 4 (95% CI 2-16) in patients who were in DAS28 remission at 6 months but lost it later; and by 6 (95% CI 2-10) in patients who were not in remission at 6 months., Conclusion: A remarkable proportion of patients with early RA treated with combinations of DMARD were in remission at 2 years, and remission was more often sustained compared to patients treated with a single DMARD. Sustained remission protects against radiographic joint damage.

Objective: To investigate the influence of individual patient risk profiles on the value of the HLA-DRB1 shared epitope (SE) as a predictor of severe erosive damage in rheumatoid arthritis (RA)., Methods: Patient characteristics, clinical signs and symptoms, rheumatoid factor (RF) status, and HLA-DRB1 genotypes were available for 154 Caucasian women with RA. Risk profiles were defined by non-genetic factors that predict severe erosive disease. The additional value of the SE was defined by the likelihood ratios (LR) of SE presence and absence, which were calculated at the individual patient level., Results: In the total population, the LR of SE presence was 1.42 and the LR of SE absence was 0.37, corresponding to an odds ratio of 3.9, indicating a substantially higher risk of severe erosive disease in those with the SE compared to those without. The LR of SE presence and absence varied depending on the risk profile of the women, from 1.01 to 2.25 for SE presence and 0.22 to 0.49 for SE absence. Considering all the patient characteristics, SE status was most significantly related to RF status. Consequently, the LR of SE presence and absence were higher for RF-negative women compared to RF-positive women (SE presence 1.77 vs 1.40, p < 0.001 and SE absence 0.38 vs 0.30, p < 0.001)., Conclusion: The additional value of SE testing for predicting severe erosive disease varies according to patient risk profiles. Given the likely availability of genetic and other novel tests in the future, information about the additional value of test results is needed to ensure the optimal use of such testing in the management of RA.

Objective: The possibility of predicting the effectiveness of intraarticular injection of high molecular weight hyaluronan (HA) was investigated using biological markers., Methods: In 32 patients with osteoarthritis (OA) of the knee, 38 knees were treated with HA injection, and the clinical symptoms were evaluated using the Japanese Orthopaedic Association (JOA) score and pain visual analog scale (VAS). The concentrations of chondroitin 6-sulfate, 4-sulfate (C6S, C4S), and aggrecan were measured in synovial fluid collected at the time of initiation of injection. The relationship between the biological markers and the improvement of clinical symptoms after injection for 1 month was investigated., Results: C6S/C4S and concentration of aggrecan decreased after injection, although these decreases were not significant. Positive correlations were noted between the concentrations of C6S and aggrecan before HA injection and the improvement of the JOA score after injection; however, radiological OA stage had no significant relation with improvement both of the JOA score and VAS., Conclusion: It has been reported that the concentration of aggrecan-derived fragments in synovial fluid decreases with advancement of the OA stage, reflecting decreases in the amount of residual cartilage and suppression of chondrocyte metabolism. Our findings suggested that HA injection exhibits a greater clinical effect in cases with a high intraarticular aggrecan fragment concentration, i.e., cases in which a high amount of residual cartilage and chondrocyte metabolic activity remain. The biological markers were useful in predicting the effectiveness of HA injection for OA of the knee.

Objective: To evaluate the ability of baseline hand radiographs to predict the diagnosis 2 years later in a cohort of patients with early arthritis., Methods: A total of 258 patients with arthritis onset within the previous year were evaluated. At baseline, all patients underwent a standardized evaluation including laboratory tests and radiographs. Hand radiographs were read by a blinded observer who used a standardized procedure for detecting features of crystal deposition diseases and rheumatoid arthritis (RA). After 30 +/- 11.3 months, the final diagnosis was established by a panel of rheumatologists. All radiographs were evaluated., Results: Significant associations were found between radiographic features and a clinical diagnosis of RA, calcium pyrophosphate dihydrate (CPPD) arthritis, and hydroxyapatite arthritis. No radiographic abnormalities suggesting psoriatic arthritis or gout were seen. The sensitivities of hand radiographs for diagnosing CPPD or hydroxyapatite arthritis ranged from 80% to 100%. Baseline hand radiographs suggested the final diagnosis in 31/258 patients, including 21 (22.5%) of the 93 patients with RA, 10 of the 11 (91%) patients with CPPD or hydroxyapatite deposition disease, and none of the patients with other disorders. Sensitivity was 29%, specificity 86.5%, positive predictive value 61%, and negative predictive value 63%., Conclusion: In our cohort of patients with recent arthritis, the overall performance of hand radiographs in predicting a diagnosis 2 years later was modest. However, they had an excellent diagnostic value for calcium deposition diseases.

Objective: There is little information on the natural history of patients with rheumatoid arthritis (RA) and associated interstitial lung disease (ILD). Cryptogenic fibrosing alveolitis (CFA) is known to have a poor longterm prognosis, and we compared the 2 conditions through a longitudinal prospective study., Methods: We previously compared baseline clinical, physiological, and radiological characteristics in 18 RA-ILD patients with 18 case controls with CFA. Clinical, physiological, and radiological assessment was repeated in all survivors at 5 years, and data on treatment and mortality were collected., Results: The median age in each group was 77 years and 10 patients in each group were male. More patients with RA-ILD survived to 5 years (8 RA-ILD vs 2 CFA; p = 0.03), and median survival was significantly longer for patients with RA-ILD (60 mo) compared to CFA (27 mo; p

Objective: To describe radiographic findings at disease onset and 3-year followup in patients with juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to assess radiographic progression and its predictors, and to prospectively assess clinical outcome and predictors of persistent disease at 3-year followup., Methods: A total of 197 patients with JRA/JSpA were examined every 6 months for 3 years. Radiographic examination was performed at baseline and 3-year followup of knees and ankles (all patients) and of other joints on clinical indication. Remission was defined as minimum 6 months without medication and no clinical signs of active disease., Results: Radiographic abnormalities were found in 88% of the patients at onset and in 81% after 3 years. Frequency of swelling/osteoporosis decreased and frequency of abnormal growth increased from baseline to followup. Knees, hands, and wrists had most frequently radiographic abnormalities. Radiographic progression occurred in 38% of the patients. Joints with swelling/osteoporosis on radiographs, young age, and a large number of mobility-restricted joints at baseline were predictors of radiographic progression. At 3 years, 26% of the patients were in remission and 75% had been treated with disease-modifying antirheumatic drugs. Reduced well-being, a large number of active joints and negative antinuclear antibody at baseline were predictors of persistent disease after 3 years., Conclusion: After 3 years most patients had radiographic abnormalities and persistent disease. Young age, many affected joints, reduced well-being, and negative antinuclear antibody at onset increased the risk of radiographic progression and persistent disease after 3 years.

Objective: "Blind" shoulder injections are often inaccurate and infiltrate untargeted structures. We tested a hypothesis that optimizing certain anatomical and positional factors would improve accuracy and reduce dispersal., Methods: We evaluated one subacromial and one glenohumeral injection technique on cadavers., Results: Mean accuracy was 91% for subacromial-targeted and 74 and 91% (worst- and best-case scenarios) for joint-targeted injections. Mean dispersal was 19% for subacromial-targeted and 16% for joint-targeted injections. All results bettered those reported previously., Conclusion: These "optimized" techniques might improve accuracy and limit dispersal of blind shoulder injections in clinical situations, benefiting efficacy and safety. However, evaluation is required in a clinical setting.

Children with juvenile spondyloarthropathy, classified as enthesitis-related arthritis (ERA) under the International League of Associations for Rheumatology classification of juvenile idiopathic arthritis, usually experience both arthritis and enthesitis. Treatment with anti-tumor necrosis factor-alpha (TNF-alpha) agents has resulted in dramatic clinical improvement. Radiologic imaging methods useful in the detection, diagnosis, and grading of arthritis and enthesitis include magnetic resonance imaging and ultrasonography. We describe the serial radiologic improvements of arthritis and enthesitis in a child with ERA in response to treatment with the anti-TNF-alpha agent etanercept.

Objective: Clinical and radiographic responses were evaluated in patients with psoriatic arthritis (PsA) treated for up to 2 years with etanercept., Methods: Patients were previously randomized to receive placebo or etanercept in a double-blind study and chose to participate in the current open-label extension phase. All patients received etanercept 25 mg twice weekly. Radiographic progression was determined at baseline, 1 year, and 2 years using the Sharp method modified to include joints frequently affected in PsA. Arthritis and psoriasis responses were determined using American College of Rheumatology 20% (ACR20) improvement criteria, PsA response criteria (PsARC), and the psoriasis area severity index (PASI)., Results: Of 205 patients randomized, 169 entered open-label, and 141 [71 randomized to receive placebo (placebo/etanercept) and 70 randomized to receive etanercept (etanercept/etanercept)] had radiographic data available for analysis at 2 years. ACR20 criteria, PsARC, and PASI 50 criteria were met by 64%, 84%, and 62%, respectively, of etanercept/etanercept patients at the end of the 48-week open-label period. Placebo/etanercept patients achieved comparable results within 12 weeks that were sustained at 48 weeks (63%, 80%, and 73%). Radiographic progression was inhibited in the etanercept/ etanercept patients (mean adjusted change in total Sharp score of -0.38 from baseline to 2 yrs). In placebo/etanercept patients, disease progression was inhibited once patients began receiving etanercept (mean adjusted change of -0.22 from 1 year to 2 years). Adverse event rates were similar to those observed during randomized phase, with only one serious adverse event deemed possibly related to etanercept., Conclusion: These data demonstrate a sustained benefit of etanercept treatment, including inhibition of radiographic progression, in patients with PsA.

Objective: The study of psoriatic arthritis (PsA) is hampered by the absence of a widely accepted, validated case definition. We investigated whether the physician's opinion can be used as a gold standard when developing classification criteria for peripheral joint PsA., Methods: UK rheumatologists who had published on PsA and attendees at 3 international meetings on PsA held in the UK were polled by questionnaire. There were 3 phases. The first questionnaire asked whether rheumatologists believed in the construct of PsA. The second survey developed a list of features thought to distinguish patients with PsA from other forms of peripheral arthritis. The final phase was development of a series of 61 "paper" patients with various combinations of the features of PsA. The paper patients were assessed by 15 rheumatologists who were asked whether, in their opinion, the patient had PsA. Latent class analysis was used to identify subgroups of patients and cross-tabulations were used to identify which clinical and laboratory features were associated with each subgroup., Results: Rheumatologists agreed on the construct of PsA and that not all patients with psoriasis and an inflammatory polyarthritis have PsA. Latent class analysis identified 3 classes, corresponding to definite PsA; a middle group that was very likely to be given a diagnosis of PsA by some rheumatologists (high diagnosers), but unlikely to be given the diagnosis by others (low diagnosers); and a third group corresponding to "probably not PsA.", Conclusion: For the group of patients with "definite PsA" the physician's opinion can be taken as the gold standard when developing classification criteria. However, for patients in the "middle group" there will always be disagreement with the gold standard whether the standard is based on the opinion of the high diagnosers or the low diagnosers.

Synovial tissue analysis has considerable potential for future randomized controlled trials (RCT). The synovial membrane is the target tissue in treatment strategies of rheumatoid arthritis and other arthropathies. Effective modulation of synovitis is critical when attempting to control symptoms and signs, to prevent joint damage, and to maintain function. In RCT, the systematic evaluation of changes in synovial tissue after commencing treatment enables identification of an early therapeutic effect, using relatively small numbers of patients. This special interest group is working on establishing the evidence to have this endpoint meet the OMERACT filter criteria.

Measurement of radiographic abnormalities in metric units has been reported by several investigators during the last 15 years. Measurement of joint space in large joints has been employed in a few trials to evaluate therapy in osteoarthritis. Measurement of joint space width in small joints has been reported by several investigators but has not yet found a place in clinical trials in rheumatoid arthritis or osteoarthritis. We review methods for measuring joint space width in finger, toe, and wrist joints; special attention is given to how the joint edges are found, the method used to measure distance between joint margins, size of an area of the sampled joint, and reproducibility of measurements. Methods for measurement of erosion size, which have had less attention, are briefly discussed.

Objective: To characterize the clinical, radiological, and diagnostic features of reactive arthritis (ReA) in indigenous Black Zambians with human immunodeficiency virus (HIV) infection., Methods: Consecutive patients attending an arthritis clinic over a 5-year period were studied prospectively. Those who satisfied diagnostic criteria for ReA were analyzed., Results: In total, 170 patients satisfied the ESSG criteria for ReA; 71 (45 men, 26 women) had one or more extraarticular manifestations; 30% had enteroreactive and 14% uroreactive disease. Only 59% of patients had the diagnostic features of ReA at presentation. The initial diagnosis was undifferentiated spondyloarthropathy (uSpa) in 20%, other ReA in 14%, and "arthritis alone" in 7%. Of 65 (42 men, 23 women) patients tested, 94% were HIV-positive (91% men, 100% women). In those with HIV, the arthritis was predominantly polyarticular, lower limb-predominant, and progressive; 58% of 33 with persistent disease had erosions of foot and/or hand joints (average disease duration, 24.4 mo); 6 of 10 showed early radiological spine or sacroiliac joint changes (average duration 47.7 mo). Anterior uveitis occurred in 33% of patients, while keratoderma blenorrhagicum and stomatitis occurred in 14.3% and 9.5%, respectively, of patients with enteroreactive ReA. Uroreactive ReA was more common in women. There were no significant differences in the clinical, diagnostic, or radiographic features between men and women or between those with or without a known preceding trigger., Conclusion: HIV associated ReA in Black Zambians frequently follows an accelerated course with a strong tendency to relapse, develop early erosions and joint deformity, and become chronic. The clinical, diagnostic, and radiographic features are indistinguishable from those described in the conventional (HLA-B27 related) disease, although our HIV-positive patients have a high overall frequency of uveitis, keratoderma, and onycholysis.

Objective: To investigate the role of T cell responses to type II collagen (CII) in disease progression in patients with rheumatoid arthritis (RA)., Methods: T cell proliferative responses to bovine CII by peripheral blood mononuclear cells (PBMC) from patients with early RA (duration < 5 yrs) were assayed by mixed lymphocyte culture. Clinical and laboratory variables including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were examined at the time of sampling. Radiographic damage on hand radiographs was evaluated by the method of Steinbrocker and Sharp., Results: In a cross sectional study, patients (n = 22) with positive T cell responses (stimulation index 2) had higher levels of CRP and ESR than those (n = 21) not showing T cell responses. The number of damaged joints (by Steinbrocker's method) and damaged joint scores (by Sharp's method) were significantly higher in patients with positive T cell responses than in those without. The joint space narrowing scores correlated well with T cell responsiveness to CII. Patients (n = 15) with both positive T cell responses and RA-susceptible allotypes HLA-DR1 or DR4 had higher damaged joint scores than the remainder of the patients (n = 24)., Conclusion: T cell proliferative responses to CII are associated with inflammatory activity and radiographic severity in RA. RA-susceptible allotypes positively relate to the radiographic progression associated with T cell responses to CII. Our data suggest that CII-reactive T cells may play a role in the pathogenic process of joint damage, especially in genetically susceptible patients.

Objective: To compare the detection and scoring of erosions in patients with rheumatoid arthritis (RA) using magnetic resonance (MR) and multidetector helical computerized tomographic (CT) scanning., Methods: Comparative CT and MR scans of the dominant wrist were obtained from 9 patients with RA and clinical examination was performed to assess disease activity. MR and CT scans were scored for erosions and MR scans for bone edema by 2 radiologists using a validated system. Radiographs of the hands and feet were also scored for erosions using the modified Sharp score., Results: In 117 of 135 (87%) sites there was concordance for erosions between MR and CT scans. At the remaining 18/135 sites (13%), erosions were identified by CT but not MR in 12/135 (9%) and by MR but not CT in 6/135 (4%). Partial volume artefacts on MR images and shifts in slice position were the most common reasons for erosion mismatch between MR and CT. The mean CT bone erosion score was significantly higher than the MR erosion score when individual bony sites were examined (p = 0.024), with the greatest difference being at the metacarpal bases. The total bone erosion score also tended to be higher on CT than MR [median scores of 20 (range 0-66) and 12 (0-51), respectively; p = 0.060]. MR and CT erosion scores correlated strongly with the total Sharp score (r = 0.93, p = 0.0002 and r = 0.94, p = 0.0002, respectively) and with the Disease Activity Score (MR: r = 0.77, p = 0.02; CT: r = 0.71, p = 0.03)., Conclusion: Most erosions were detected using both modalities, but erosion scores were higher on CT than MR scans, especially at the metacarpal bases. It is possible that small erosions in some regions are more easily detected by CT because of its ability to clearly delineate cortical bony margins.

Objective: To determine the baseline and longitudinal consistency in reproducibility of the semiflexed metatarsophalangeal (MTP) position in repeat examinations of patients with knee osteoarthritis (OA) recruited for a multicenter clinical trial that terminated within one year (mean duration 0.81 yr), based on precise measurements both of minimum medial tibiofemoral compartment joint space width (JSW) and of tibial inter-rim distance., Methods: Two technologists from 8 and one technologist from 14 clinical radiology units had received previous training in performing nonfluoroscopic semiflexed MTP knee examinations and in quality control criteria for film acceptance. Patients (N = 402; F = 269) were recruited from 58 rheumatology sites and referred to 22 centers, or "x-ray hubs," across North America. At baseline and at study exit, both knees were x-rayed twice on the same day. All films had quality control, and accepted films were digitized at the Central Radiographic Facility and transmitted to the Central Analysis Facility for computerized measurement of minimum medial compartment JSW and tibial inter-rim distance. JSW loss was calculated in the placebo group for the study period., Results: The median SD of the difference in JSW between same-day test/retest film pairs was 0.9 mm for 767 baseline film pairs (knees with JSW > 0 mm), and 0.08 mm for 631 exit film pairs. JSW reproducibility was unaffected by subject's sex, age, and degree of JSW loss. Among all x-ray hubs, JSW reproducibility was excellent in 14 (SD < 0.1 mm), good in 6 (0.1 < SD < 0.2 mm), and moderate in 2 hubs (0.2 < SD < 0.3 mm). No statistical difference was found in technologists' ability either in positioning OA knees or in their test/retest reproducibility in repositioning joints at baseline and at study exit. JSW did not alter significantly during the study period., Conclusion: The protocol for the semiflexed MTP knee position provides a highly reproducible method for anatomically repositioning the knee and for measuring JSW, necessary for OA clinical trials. It is a simple method that can be employed readily at clinical radiology units, as shown by the similarity in JSW precision between x-ray hubs. The results from this large dataset show that throughout the study precise measurements of JSW were obtained from same-day repeat radiographs, findings that together with previous single-center studies confirm the reliability of this method for clinical trial use.

Objective: To investigate the relationship between osteocalcin (OC), a marker of bone formation, and the recently developed serum marker of bone resorption, beta-C-telopeptide (beta-CTx), and radiographic damage in patients with early oligo- and polyarthritis., Methods: Patients with peripheral arthritis of > or = 2 joints and < 2 years of symptom duration were studied. The OC and beta-CTx concentrations at baseline were correlated with disease activity and radiographic damage at baseline, and with radiographic progressive disease after 2 years (delta Sharp/van der Heijde score > or = 5). The additional value of serum bone metabolism markers to predict radiographic progressive disease was compared to that of established prognostic factors by multivariate logistic regression analysis., Results: Two hundred seventy-nine patients (67% female; median age 56 yrs, range 18-83) were included in the study, of whom 73% were diagnosed with rheumatoid arthritis (RA). Baseline levels of beta-CTx (p < 0.05) were significantly correlated with baseline radiographic damage whereas OC was not. beta-CTx was also significantly (p < 0.001) related to measures of disease activity like erythrocyte sedimentation rate, C-reactive protein, and the disease activity score DAS28. Radiographic progressive disease after 2 years corresponded univariately with increased levels of beta-CTx (p < 0.001), but not with OC. In multivariate analysis, beta-CTx was not superior to other measures of radiographic progressive disease such as autoantibodies and disease activity., Conclusion: Increased serum levels of the bone turnover marker beta-CTx are associated with radiographic damage at baseline and radiographic progression after 2 years. However, beta-CTX is less predictive than markers already in use.

Objective: Intraarticular osteoid osteoma is uncommon and presents diagnostic difficulties, which are important for both rheumatologists and orthopedic surgeons. Clinical symptoms, imaging procedures, differential diagnostic problems, and treatment results of intraarticular as compared with extraarticular osteoma are analyzed in this retrospective study., Methods: Nineteen patients with intraarticular osteoid osteomas (Group A), with a mean followup period of 34 months, are compared with 15 others with extraarticular lesions (Group B)., Results: Nine intraarticular tumors were located in the hip, 3 in the elbow, 6 in the ankle, and one in the first metatarsal head. The nonspecific symptoms in Group A, such as chronic synovitis, decreased range of motion, joint effusion, contractures, and lack of the intense perifocal sclerotic margin on radiographs, led to significant delay in diagnosis (on average 26.6 mo in Group A, 8.5 mo in Group B). The extreme variety of previous diagnoses at referral reflect the problems of differential diagnosis. A detectable nidus is often absent on conventional radiograph. Bone scintigraphy is unspecific and often fails to visualize the nidus. Computed tomography scans were accurate in two-thirds of the intraarticular and in 90% of extraarticular cases. Magnetic resonance image findings, although sometimes controversial, provided essential additional information for the correct diagnosis and therapy., Conclusion: Clinical symptoms and imaging signs of intraarticular osteoid osteomas were significantly different from the classical hallmarks of extraarticular lesions. The 10% intraarticular occurrence of osteoid osteomas in this series is not as rare as some investigators suggest. The radiological and clinical findings are uncharacteristic and misleading, and the lesions are difficult to identify. Careful search for history data, such as nocturnal pain and positive salicylate test, in addition to extensive imaging procedures, led to the correct diagnosis prior to surgery in two-thirds of our patients with intraarticular osteoid osteomas.