Showing papers in "The Journal of Rheumatology in 2007"

Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis.

Abstract: Objective. Macrophage activation syndrome (MAS) is a well described, but purportedly uncommon manifestation of systemic juvenile idiopathic arthritis (SJIA). There is evidence to suggest that macrophage activation is integral to the pathogenesis of SJIA. Accordingly, many patients with SJIA may have evidence of mild MAS that is not appreciated clinically. We investigated the prevalence of occult MAS in children with SJIA by reviewing bone marrow aspirates (BMA). Methods. Patients diagnosed with SJIA who underwent bone marrow aspiration were identified retrospectively. Patients admitted with a diagnosis of fever of unknown origin and discharged with a diagnosis other than SJIA or malignancy, and who had a BMA, were identified as controls. The BMA were reviewed by a single hematopathologist for evidence of MAS, ranging from activated macrophages to frank hemophagocytic cells. Results. Eight of 15 (53%) patients with SJIA had BMA suggestive of MAS. Two of 15 patients (13%) were diagnosed clinically with MAS. Three patients (20%) were noted to have frank hemophagocytosis, only one of whom was diagnosed with MAS clinically. There were no statistically significant differences in the laboratory values for the patients with and without evidence of MAS on BMA. There was no evidence of increased macrophage activity or hemophagocytosis in any of the control BMA. Conclusion. Occult MAS appears to be common in patients with SJIA who undergo BMA. This suggests that macrophage activation may be integral to the pathogenesis of SJIA, with implications for treatment.

Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication.

Abstract: OBJECTIVE: Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA. METHODS: We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. RESULTS: Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%). CONCLUSION: The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.

Epidemiology of general joint hypermobility and basis for the proposed criteria for benign joint hypermobility syndrome: review of the literature.

Abstract: OBJECTIVE: This literature review of generalized joint hypermobility (GJH) syndromes discusses information regarding sex-, age-, and race-related factors from publications that specifically document validated GJH criteria. METHODS: We present an analysis of criterion-referenced connections that identify similarities among major and minor clinical criteria that identify both GJH and benign joint hypermobility syndrome (BJHS). In our search, we found considerable empirical evidence that supports an increased prevalence of hypermobility among children, women, and certain racial groups. Two commonly used clinical assessment tools, the Carter and Wilkinson criteria (>or= 3 positive tests out of 5) and the Beighton method (>or= 4 positive tests out of 9), are the sources of these data. BJHS is diagnosed through a set of major and minor criteria - a combination of symptoms and objective findings -- that include arthralgia, back pain, spondylosis, spondylolysis/spondylolisthesis, joint dislocation/subluxation, soft tissue rheumatism, marfanoid habitus, abnormal skin, eye signs, varicose veins or hernia or uterine/rectal prolapse. RESULTS: Clinically, there is some evidence that arthralgia, the proposed BJHS major criterion, is a major component of alleged hypermobility-related problems. In contrasting, there is no clear evidence that proposed BJHS minor diagnostic criteria are associated with hypermobility-related problems. An empirical correlation between hypermobility and osteoarthritis is possible, but so far unproven. There are no randomized controlled studies regarding effects of existing treatments. CONCLUSION: Generalized hypermobility is both sex- and age-related. Racial differences are also identifiable. The existence of BJHS can be accepted using present criteria.

Patient perspective: fatigue as a recommended patient centered outcome measure in rheumatoid arthritis.

Abstract: The Patient Perspective Workshop at OMERACT 8 considered evidence for the importance of fatigue to patients with rheumatoid arthritis (RA) and whether measurement of fatigue meets the requirements of the OMERACT filter. The workshop participants included 20 patients from 10 countries and 60 other OMERACT participants. Introductory papers and detailed notes for discussion group members set out the evidence from the literature and from recent analyses of clinical study data available to several participants. The workshop concluded that fatigue is a symptom that is important to patients, is commonly reported by patients, is often severe, can be measured by several current instruments that pass the OMERACT filter, is responsive to some interventions, and provides information additional to that commonly obtained from currently used outcomes. The final OMERACT plenary session endorsed by a very large majority (89%) the proposal that, in addition to the "core set" of outcome measures currently in widespread use, fatigue should be measured in future studies of RA whenever possible.

Consensus on a core set of domains for psoriatic arthritis

Abstract: A psoriatic arthritis (PsA) module was convened at OMERACT 8 in order to achieve consensus on the core domains that should be included in randomized controlled trials and longitudinal observational cohorts of subjects with PsA. Following a plenary session at which current status of measures used to assess PsA were reviewed, and discussion at breakout groups, the group achieved consensus on 6 core domains: peripheral joint activity, skin activity, pain, patient global assessment, physical function, and health-related quality of life. In addition the following domains were considered important but not mandatory: spinal disease, dactylitis, enthesitis, fatigue, nail disease, radiography, physician global assessment, and acute-phase reactants. A research agenda was proposed to include development and validation of instruments for the domains where none existed, and in particular further research was recommended for the following areas: magnetic resonance imaging and ultrasound of joints, enthesitis, skin and synovial tissue analysis, and "participation."

Frontal plane knee alignment: a call for standardized measurement.

Abstract: Evaluations of knee alignment are useful in the diagnosis of arthritic conditions affecting the knee joint, serving also as a guide for conservative management and surgical planning1-5. They are also fundamental to various aspects of musculoskeletal research. Recently, there has been great interest in frontal plane alignment measures related to the pathogenesis of knee osteoarthritis (OA)6,7. Several approaches have been proposed over the years to describe and measure alignment1-5,8-10, but the differences between them have made it difficult to compare or correlate the results of independent studies. Toward a standard approach to the measurement and reporting of alignment data that may be equally applicable to clinicians and researchers, we discuss a system of measurements based on geometric analysis of the femur, tibia, and knee joint surfaces. We also discuss a standardized methodology for measurement and computation of these parameters.

Risk factors for surgical site infections and other complications in elective surgery in patients with rheumatoid arthritis with special attention for anti-tumor necrosis factor: a large retrospective study.

Abstract: OBJECTIVE: To identify risk factors for surgical site infection (SSI) in patients with rheumatoid arthritis (RA) with special attention for anti-tumor necrosis factor (anti-TNF) treatment. METHODS: All patients with RA who had undergone elective orthopedic surgery since introduction of anti-TNF were included in a retrospective parallel-cohort study with a one-year followup. Primary endpoint was a SSI according to the 1992 Centers for Disease Control and Prevention criteria and/or antibiotic use. Cohort 1 did not use anti-TNF, cohort 2 used anti-TNF but had either stopped (2A) or continued anti-TNF preoperatively (2B), the cutoff point being set at 4 times the half-life time of the drug. Infection rates were compared between cohorts, and logistic regression analysis was performed to examine risk factors. RESULTS: In total, 1219 (768 patients) procedures were included, and crude infection risks were 4.0% (41/1023), 5.8% (6/104), and 8.7% (8/92) in cohorts 1, 2A, and 2B, respectively. Elbow surgery (OR 4.1, 95% CI 1.6-10.1), foot/ankle surgery (OR 3.2, 95% CI 1.6-6.5), and prior skin or wound infection (OR 13.8, 95% CI 5.2-36.7) were associated with increased risk of SSI, whereas duration of surgery (OR 0.42, 95% CI 0.23-0.78) and sulfasalazine use (OR 0.21, 95% CI 0.05-0.89) were associated with decreased risk. Perioperative use of anti-TNF was not significantly associated with an increase in SSI rates (OR 1.5, 95% CI 0.43-5.2). CONCLUSION: The most important risk factor for SSI is history of SSI or skin infection. Although our study was not powered to detect small differences in infection rates, perioperative continuation of anti-TNF does not seem to be an important risk factor for SSI.

Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab.

Abstract: OBJECTIVE: This study compared the immunogenicity of influenza and pneumococcal vaccines in adult patients with rheumatoid arthritis (RA) receiving adalimumab or placebo. METHODS: In this double-blind, randomized, multicenter study, patients received adalimumab or placebo on Days 1, 15, and 29. Pneumococcal and influenza vaccines were administered on Day 8 (vaccine baseline). Vaccine response (> or = 2-fold titer increase from baseline in > or = 3 of 5 pneumococcal antigens and > or = 4-fold titer increase from baseline in > or = 2 of 3 influenza antigens) and protective antibody titers (> or = 1.6 microg/ml pneumococcal antibody concentration to > or = 3 of 5 antigens and > or = 1:40 influenza antibody titer to > or = 2 of 3 antigens) were analyzed 4 weeks9 postvaccination. RESULTS: Following pneumococcal vaccination, percentages of patients achieving a vaccine response were similar in the adalimumab and placebo groups [37.4% and 40.4%, respectively; 95% CI (confidence interval) -16.2%, 10.3%]. Percentages of patients with protective antibody titers were similar in both treatment groups (adalimumab: 85.9%, placebo: 81.7%). Following influenza vaccination, percentages of patients achieving a vaccine response were lower with adalimumab than placebo (51.5% and 63.3%, respectively; 95% CI -25.2%, 1.6%)--a result explained by the subgroup of patients with preexisting protective antibody titers at baseline. For patients without protective antibody titers at baseline, response rates were similar in the 2 groups (adalimumab: 73.3%, placebo: 73.9%). Percentages of patients with protective antibody titers were similar in both treatment groups (adalimumab: 98%, placebo: 94.5%). CONCLUSION: Patients with RA treated with adalimumab can be effectively and safely immunized with pneumococcal and influenza vaccines.

Sildenafil for pulmonary arterial hypertension associated with connective tissue disease.

Abstract: OBJECTIVE: Pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) is difficult to manage, and has a poor prognosis. The phosphodiesterase-5 inhibitor sildenafil citrate enhances vasodilatation, has antiproliferative effects, and is effective in the treatment of PAH. We examined the efficacy and safety of oral sildenafil in patients with PAH-CTD. METHODS: In a 12-week, double-blind study (SUPER-1), 278 patients with PAH were randomized to oral placebo, sildenafil 20 mg, sildenafil 40 mg, or sildenafil 80 mg 3 times daily (tid). In a post-hoc subgroup analysis of 84 patients with PAH-CTD, exercise capacity, hemodynamic measures, World Health Organization functional class, and tolerability were assessed. RESULTS: Forty-five percent of the patients had scleroderma, 23% had systemic lupus erythematosus, and the rest (32%) were categorized as other. Patients were predominantly functional class II (38%) or III (61%) at baseline. Sildenafil-treated patients exhibited mean increases in 6-minute walk distance at Week 12 of 42 m (95% CI 20, 64) for 20 mg, 36 m (95% CI 14, 58) for 40 mg, and 15 m (95% CI -24, 54) for 80 mg, while placebo-treated patients exhibited a mean decrease of 13 m (95% CI -36, 10). Improvement of at least 1 functional class occurred in 29%-42% of sildenafil-treated patients, compared to 5% for placebo. Significant improvements in mean pulmonary arterial pressure and pulmonary vascular resistance were observed with sildenafil 20 mg, and sildenafil was generally well tolerated. CONCLUSION: In patients with PAH-CTD, sildenafil improves exercise capacity, hemodynamic measures (at the 20 mg dose), and functional class after 12 weeks of treatment.

Differences in atherosclerotic coronary heart disease between subjects with and without rheumatoid arthritis

Abstract: OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular diseases (CVD). We compared the histologic features of coronary artery disease in patients with RA and non-RA controls. METHODS: Forty-one RA patients who died and underwent autopsy between 1985 and 2003 were matched to 82 non-RA controls of the same age and sex with similar history of CVD and autopsy date. Coronary arteries were submitted for histologic evaluation. The grade of stenosis was evaluated in each artery. The numbers of vulnerable plaques and acute coronary lesions were counted. The composition of a representative stable and vulnerable plaque from each vessel was evaluated. Chi-square tests were used to compare differences between groups. RESULTS: Patients and controls had similar age at death (mean 79 yrs) and 61% were female in both groups. Overall, there was no significant difference in grade of stenosis or number of acute coronary lesions. Among subjects with CVD, 54% of controls had grade 3-4 lesions in left main artery versus only 7% of patients (p = 0.023). Vulnerable plaques in left anterior descending (LAD) artery were significantly more common in patients than controls (p = 0.018). Inflammation was observed more frequently in patients, in both the media of left circumflex (p = 0.005) and adventitia of LAD artery (p = 0.024). Similar trends were seen for subjects with heart failure. CONCLUSION: There was less histologic evidence of atherosclerosis but greater evidence of inflammation and instability in RA patients compared to controls. These differences suggest that the mechanisms responsible for cardiovascular morbidity and mortality may be different in patients with RA.

Natural history of ischemic digital ulcers in systemic sclerosis: single-center retrospective longitudinal study.

Abstract: OBJECTIVE: To describe the natural history of ischemic digital ulcers (DU) in systemic sclerosis (SSc). METHODS: This single-center, retrospective, longitudinal study identified patients by demographic data, SSc history and type, Rodnan score, tobacco use, presence of autoantibodies, ongoing treatment, and DU history. RESULTS: One hundred three patients were enrolled, 46 with DU history and 57 without; 2 with DU were excluded. The mean duration of followup from the first non-Raynaud SSc symptoms was 12.3 +/- 6.3 years in patients with DU history and 12.1 +/- 7.0 years in patients without. In 43% of cases, first DU occurred within 1 year following first non-Raynaud SSc symptoms, and within 5 years in 73% of cases. In a multivariate analysis, younger patients at occurrence of first non-Raynaud SSc symptoms (HR = 0.77 per each 5 years older, 95% CI 0.66-0.90) with higher Rodnan scores (HR = 1.21 per 5 points, 95% CI 1.05-1.47) experienced earlier DU occurrences, which were delayed by vasodilator therapy (HR = 0.17, 95% CI 0.09-0.32). Patients with shorter durations between first and second DU episodes, particularly with a second episode within 2 years of the first, experienced a higher yearly incidence of DU episodes (0.85 +/- 0.57 and 0.48 +/- 0.26, respectively, if less or more than 2 yrs; p = 0.04). Throughout the duration of followup, the incidence of finger amputation was 1.2% per patient-year in patients with DU history. CONCLUSION: Patients who are young at first sign of SSc, with high Rodnan scores and without vasodilator therapy, are at high risk of developing DU. Development of DU typically occurred within 5 years of the first non-Raynaud clinical symptom of SSc in the majority of patients.

Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy.

Abstract: OBJECTIVE: To demonstrate the safety and efficacy of adalimumab for the treatment of active psoriatic arthritis (PsA) in patients with an inadequate response to disease modifying antirheumatic drugs (DMARD). METHODS: In a placebo controlled, double-blind, randomized, multicenter study, patients were treated for 12 weeks with subcutaneous injections of adalimumab 40 mg every other week (eow) or placebo, followed by a period of open-label treatment with adalimumab 40 mg eow. The primary efficacy endpoint was the percentage of patients who met the American College of Rheumatology (ACR20) core criteria at Week 12. Secondary efficacy measures included the modified Psoriatic Arthritis Response Criteria (PsARC) and assessments of disability, psoriatic lesions, and quality of life. For missing data, nonresponder imputation was used for ACR and PsARC scores and last observation carried forward for other measures. RESULTS: A total of 100 patients received study drug (51 adalimumab, 49 placebo). At Week 12, an ACR20 response was achieved by 39% of adalimumab patients versus 16% of placebo patients (p = 0.012), and a PsARC response was achieved by 51% with adalimumab versus 24% with placebo (p = 0.007). At Week 12, measures of skin lesions and disability were statistically significantly improved with adalimumab. After Week 12, open-label adalimumab provided continued improvement for adalimumab patients and initiated rapid improvement for placebo patients, with ACR20 response rates of 65% and 57%, respectively, observed at Week 24. Serious adverse events had similar frequencies during therapy with placebo (4.1%), blinded adalimumab (2.0%), and open-label adalimumab (3.1%). No serious infections occurred during adalimumab therapy. CONCLUSION: In this study of patients who had active PsA and a previous, inadequate response to DMARD therapy, adalimumab was well tolerated and significantly reduced the signs, symptoms, and disability of PsA during 12 weeks of blinded and 12 weeks of open-label therapy. Adalimumab also improved psoriasis in these patients.

Incidence of tuberculosis in Korean patients with rheumatoid arthritis (RA): effects of RA itself and of tumor necrosis factor blockers.

Abstract: OBJECTIVE: To elucidate the incidence rate and relative risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) and in patients with RA treated with tumor-necrosis-factor (TNF) blockers in Korea. METHODS: Using data from the Korean National Tuberculosis Association (KNTA) as a control and data from a single-center cohort of patients with RA, we conducted an evaluation of 1285 patients with RA not exposed to TNF blockers and reviewed medical records of 90 and 103 patients with RA treated with infliximab and etanercept, respectively, between 2001 and 2005. RESULTS: The mean incidence rate of TB, reported by the KNTA, was 67.2 per 100,000 person years (PY) from 2001 to 2004. In the TNF-blocker-naive RA cohort, 9 cases of TB developed during 3497 PY of followup (257 per 100,000). In the infliximab-treated RA group, 2 cases of TB developed during 78.17 PY of followup (2558 per 100,000 PY), and there was no case of TB during 73.67 PY of followup in the etanercept-treated RA group. The risk of TB was higher in RA patients not treated with TNF blockers (sex- and age-adjusted risk ratio 8.9; 95% confidence interval 4.6-17.2), and in those treated with infliximab (sex- and age-adjusted risk ratio, 30.1; 95% confidence interval, 7.4-122.3) compared with the general Korean population. CONCLUSION: The risk of TB infection is 8.9-fold higher in Korean patients with RA and 30.1-fold higher in RA patients treated with infliximab, compared with the general Korean population.

Minimal clinically important improvement and patient acceptable symptom state for subjective outcome measures in rheumatic disorders.

Abstract: The concepts of minimal clinically important improvement (MCII) and patient acceptable symptomatic state (PASS) could help in interpreting results of trials involving patient-reported outcomes by translating the response at the group level (change in mean scores) into more clinically meaningful information by addressing the patient level as "therapeutic success (yes/no)." The aims of the special interest group (SIG) at OMERACT 8 were to discuss specific issues concerning the MCII and PASS concepts, especially the wording of the external anchor questions used to determine the MCII and PASS estimates, and to move toward a consensus for the cutoff values to use as the MCII and PASS in the different outcome criteria. The purpose of this SIG at OMERACT 8 was to inform participants of the MCII and PASS concepts and to agree on MCII and PASS values for pain, patient global assessment, and functional impairment.

Conservative management of mechanical neck disorders : A systematic review

Abstract: OBJECTIVE: To determine if conservative treatments (manual therapies, physical medicine methods, medication, and patient education) relieved pain or improved function/disability, patient satisfaction, and global perceived effect in adults with acute, subacute, and chronic mechanical neck disorders (MND) by updating 11 systematic reviews of randomized controlled trials (RCT). METHODS: Two independent authors selected studies, abstracted data, and assessed methodological quality from computerized databases. We calculated relative risks and standardized mean differences (SMD) when possible. In the absence of heterogeneity, we calculated pooled effect sizes. RESULTS: We studied 88 unique RCT. The mean methodological quality scores were acceptable in 59% of the trials. We noted strong evidence of benefit for maintained pain reduction [pooled SMD -0.85 (95% CI -1.20, -0.50)], improvement in function, and positive global perceived effect favoring exercise plus mobilization/manipulation versus control for subacute/chronic MND. We found moderate evidence of longterm benefit for improved function favoring direct neck strengthening and stretching for chronic MND, and for high global perceived effect favoring vertigo exercises. We noted moderate evidence of no benefit for botulinium-A injection [pooled SMD -0.39 (95% CI -01.25, 0.47)]. We found many treatments demonstrating short-term effects. CONCLUSION: Exercise combined with mobilization/manipulation, exercise alone, and intramuscular lidocaine for chronic MND; intravenous glucocorticoid for acute whiplash associated disorders; and low-level laser therapy demonstrated either intermediate or longterm benefits. Optimal dosage of effective techniques and prognostic indicators for responders to care should be explored in future research.

Are diagnostic criteria for general joint hypermobility and benign joint hypermobility syndrome based on reproducible and valid tests? A review of the literature.

Abstract: OBJECTIVE: In this review we focus on current knowledge of the reliability of tests and diagnostic criteria for generalized joint hypermobility (GJH) and benign joint hypermobility syndrome (BJHS). METHODS: Currently, The British Society of Rheumatology recommends the Beighton scoring system. With this approach, GJH is judged present when 4 or more of 9 tests are positive. Curiously, only one inter/intrarater reproducibility study is available and it uses a cutoff level of 6, rather than the Beighton-recommended 4 positive tests. RESULTS: Using a 6 cut level, intra- and interobserver kappa scores were 0.75 and 0.78, respectively. Beighton scoring recommendations have been correlated with a global joint mobility index as well as with 2 other scoring systems, the Carter and Wilkinson, and the Rotes-Querol. All illustrate high concurrent validity with one another. For the recently proposed Brighton criteria diagnosing BJHS no reproducibility studies exist. In the latter, the recommendations reflect high nosographic sensitivity and specificity while predictive values for positive test scores are poor. CONCLUSION: In general, the reproducibility of the various tests seems to be good, especially when performed by experienced rheumatologists.

Tumor necrosis factor-alpha blocker in treatment of juvenile idiopathic arthritis-associated uveitis refractory to second-line agents: results of a multinational survey.

Abstract: OBJECTIVE: Uveitis occurs in 10%-15% of patients with juvenile idiopathic arthritis (JIA). If topical treatment fails, second-line agents are used to control the disease. However, some patients need the addition of tumor necrosis factor-alpha (TNF-alpha) antagonist (anti-TNF). We organized a cross-sectional cohort to investigate use and efficacy of anti-TNF treatment in patients with JIA-associated uveitis. METHODS: The international pediatric rheumatology community was queried about the use and efficacy of anti-TNF in treatment of JIA-associated uveitis using an E-mail survey. RESULTS: Of the 33 responding centers following 884 patients with uveitis, only 15 centers, following 404 patients, were using anti-TNF for this indication. A total of 47 patients with JIA-related uveitis treated with anti-TNF because of an insufficient response to previous therapy were reported. The mean age of the patients was 12.5 years. The mean duration from onset of uveitis to start of anti-TNF treatment was 45.1 months. Three different anti-TNF agents were used: etanercept in 34 cases, infliximab in 25 cases, and adalimumab in 3 cases. In 12 of the 34 patients etanercept was inefficacious and patients were switched to infliximab. The final response was rated according to a composite index as 53%/12%/32%, and according to physician rating as 47%/12%/38% representing good, moderate, and poor, respectively, in the etanercept group; and 70%/30%/0% and 68%/24%/0% in the infliximab group. All 3 patients taking adalimumab were responders. Infliximab was statistically significantly more efficacious for the treatment of JIA-associated uveitis than etanercept (chi-square p = 0.004). CONCLUSION: Anti-TNF seems to be an effective treatment for refractory JIA-associated uveitis. In this cohort infliximab was more efficacious than etanercept.

Ultrasonographic measurement of tophi as an outcome measure for chronic gout.

Abstract: OBJECTIVE: To validate the usefulness of measuring tophi with ultrasonography (US) as an outcome measure for chronic tophaceous gout. METHODS: Patients with crystal-proven gout were included. To evaluate validity, intraarticular and articular deep tophi were evaluated with both magnetic resonance imaging (MRI) and US. Tophi were punctured with US guidance to evaluate face validity. Interobserver and intraobserver measurement studies were done to evaluate reliability, and to estimate the smallest detectable difference. Sensitivity to change was evaluated with a 12-month followup observational study of urate-lowering therapy. RESULTS: US detected at least one tophus in all joints where MRI found nodules considered to be tophi. There was a good correlation, but just fair agreement between measurements with US and MRI. Puncture of nodules suspected of being tophi recovered urate crystals in 83% of the procedures. Intraobserver intraclass correlation was > 0.90 for diameters and volume, while it was 0.71 to 0.83 in the interobserver study. US was found to be sensitive to change, and there was an inverse correlation between serum urate concentrations and change from baseline measurement of tophi. CONCLUSION: US measurement of tophi fulfilled the OMERACT filter for an outcome measure, although it should be tested further in randomized clinical trials.

The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis.

Abstract: OBJECTIVE: Patients with psoriasis and psoriatic arthritis (PsA) commonly have nail involvement. There is no validated psoriatic nail assessment tool. Recently, investigators developed the Nail Psoriasis Severity Index (NAPSI). Beginning with NAPSI, our goal was to validate a psoriatic nail assessment tool for use in clinical trials, and investigate correlations between nail and other PsA features. METHODS: Fingernails of 29 patients with PsA were photographed and scored. Clinical data were collected. Using the original NAPSI, analysis revealed high interrater variability of nail scores. Twenty patients9 photographs were regraded using the modified NAPSI (mNAPSI). RESULTS: The mNAPSI scores had excellent interrater reliability (Cronbach9s alpha 0.98). Nail scores and physicians9 global nail severity visual analog scores showed good inter- and intrarater correlations (Spearman9s rho 0.85 and 0.90-0.99, respectively; p

Assessment of pain in rheumatoid arthritis: minimal clinically significant difference, predictors, and the effect of anti-tumor necrosis factor therapy.

Abstract: OBJECTIVE: To compare a visual analog pain scale (VAS) with the Medical Outcomes Study Short Form-36 Health Survey (SF-36) bodily pain; to define the minimal clinically important change (MCIC) for pain in observational studies; to define clinically useful cutpoints for pain; to quantify the predictors of pain; and to estimate the effect of anti-tumor necrosis factor (TNF) therapy on pain. METHODS: Over 6 years we studied 12,090 patients with rheumatoid arthritis (RA). Pain was assessed by VAS and SF-36 pain scales. RESULTS: Compared with the SF-36 scale, the 0-10 VAS pain scale was better correlated with all clinical variables. The mean VAS score was 3.4 (standard deviation 2.8), and the best cutpoint for an "acceptable" level of pain was

Th1/Th17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy.

Abstract: OBJECTIVE: Data on synovial fluid (SF) cytokine concentrations in patients with reactive arthritis (ReA) or undifferentiated spondyloarthropathy (uSpA) are limited and contradictory. We measured levels of several proinflammatory and immunoregulatory cytokines in SF and sera from patients with ReA/uSpA. METHODS: Interleukin 17 (IL-17), IL-6, interferon-g (IFN-g), and IL-12p40, and immunoregulatory cytokines IL-10 and transforming growth factor-beta (TGF-beta) were assayed using ELISA in SF specimens from 51 patients with ReA/uSpA (ReA 21, uSpA 30), 40 patients with rheumatoid arthritis (RA), and 11 patients with osteoarthritis (OA). IL-17, IL-6, IFN-g, and IL-10 levels were also measured in paired sera samples from patients with ReA/uSpA. RESULTS: SF concentrations of IL-17, IL-6, TGF-beta, and IFN-g were significantly higher in patients with ReA/uSpA as compared to RA patients (for IL-17 median 46 pg/ml, range

Meniscal tear as an osteoarthritis risk factor in a largely non-osteoarthritic cohort: a cross-sectional study.

Abstract: OBJECTIVE: To examine the associations between meniscal tear, knee structure, osteoarthritis (OA) risk factors, radiographic change, and symptoms in a largely non-osteoarthritic cohort. METHODS: This cross-sectional study included 294 subjects with mean age 47 (SD 6) years, body mass index (BMI) 28 (SD 5), and 58% were female. Meniscal tear, knee cartilage defect score, quantitative tibial and femoral cartilage volume, and tibial plateau bone area were determined using T1-weighted fat saturated magnetic resonance images. RESULTS: In multivariable analysis, prevalence of meniscal tear was significantly associated with age (OR 1.06 to 1.12/year, all p

Descriptive epidemiology of osteoarthritis in British Columbia, Canada.

Abstract: OBJECTIVE: Osteoarthritis (OA) is a highly prevalent and often disabling disease. Data on the incidence of OA in the general population are limited. Our objectives were (1) to estimate OA prevalence and incidence rates by age and sex in a geographically defined population of 4 million people [British Columbia (BC), Canada] using an administrative database; and (2) to determine the effects of different administrative definitions of OA and observation (run-in) time on such estimates. METHODS: We used data on all visits to health professionals and hospital admissions covered by the Medical Services Plan (MSP) of BC for the fiscal years 1991-92 through 2000-01. OA was defined based on International Classification of Diseases, 9th Revision, diagnostic codes required for administrative purposes. RESULTS: The overall prevalence of OA in 2001 was 10.8%: 8.9% in men and 12.6% in women. Prevalence was higher in women in all age groups. By age 70-74 years, about one-third of men and 40% of women had OA. Incidence rates in 2000-01 were 11.7 per 1000 person-years in the total population, 10.0 in men and 13.4 in women. Rates increased linearly with age between 50 and 80 years. Both prevalence and incidence depended strongly on the definition of OA and the run-in period. CONCLUSION: Prevalence of physician-diagnosed OA in BC was slightly lower than self-reported prevalence of arthritis in population surveys. Routinely collected administrative data could be a valuable source of information for OA surveillance, but more research is needed on the validity of OA diagnosis in administrative databases.

Good clinical response, remission, and predictors of remission in rheumatoid arthritis patients treated with tumor necrosis factor-alpha blockers: the GISEA study.

Abstract: OBJECTIVE: To assess the prevalence of good clinical response and remission in rheumatoid arthritis (RA) patients with longstanding disease treated with anti-tumor necrosis factor-alpha (TNF-alpha) drugs at outpatient clinics. METHODS: Retrospective national study of 14 academic tertiary referral rheumatology medical centers. RA patients with a Disease Activity Score (DAS28) > 3.2 were defined as having active disease and could start TNF-alpha blockers. All patients received one TNF-alpha blocker plus methotrexate (10-20 mg/wk). At the third month the patients were categorized as responders or nonresponders, based on improvement of at least 0.25 of the Health Assessment Questionnaire (HAQ). Those who had improved by at least 0.25 HAQ were analyzed for possible predictors of DAS28 remission at the sixth month. RESULTS: A total of 1257 patients started TNF-alpha blockers. Of these, 591 (46.7%) reached the sixth month with an improvement of HAQ of 0.25 at the third month. In the cohort of patients reaching HAQ of 0.25, DAS28 remission was seen in 24% of rheumatoid factor (RF)-positive and 36% of RF-negative patients (p = 0.03). Logistic regression analysis for predictors of remission identified age at baseline, HAQ

Worker productivity outcome measures in arthritis.

Abstract: Arthritis is a leading cause of work disability and makes up a significant amount of the socioeconomic cost and health burden to the working age population. We discuss the measurement of worker productivity: that is, absenteeism and presenteeism. Absenteeism refers to the time missed from work due to health reasons and presenteeism refers to the time of impaired performance while at work due to health reasons resulting in productivity loss. While the term absenteeism is commonly used and has several definitions by itself, the current arthritis literature lacks the use of presenteeism as a work outcome measure in describing health states of the workers and for economic costing. Due to advanced medical management and job accommodations that allow workers to stay at work, absenteeism alone may not be enough to give us a complete picture of worker productivity. From our review, we found that the conceptualization and measurement of absenteeism and presenteeism differ. Our research agenda was to carry forward a work outcome measurement that can be used for cost calculation and that can determine levels or states of productivity loss so we can accurately measure the influence of arthritis and advance arthritis care. We recognize the need to perform psychometric testing of work outcome measures and to improve our ability to identify transitions (i.e., move in and out of a productivity state over time) made by workers with arthritis.

Scoring inflammatory activity of the spine by magnetic resonance imaging in ankylosing spondylitis: a multireader experiment.

Abstract: OBJECTIVE: Magnetic resonance imaging (MRI) of the spine is increasingly important in the assessment of inflammatory activity in clinical trials with patients with ankylosing spondylitis (AS). We investigated feasibility, inter-reader reliability, sensitivity to change, and discriminatory ability of 3 different scoring methods for MRI activity and change in activity of the spine in patients with AS. METHODS: Thirty sets of spinal MRI at baseline and after 24 weeks of followup, derived from a randomized clinical trial comparing a tumor necrosis factor (TNF)-blocking drug (n = 20) with placebo (n = 10) and selected to cover a wide range of activity at baseline and change in activity, were presented electronically in a partial latin-square design to 9 experienced readers from different countries (Europe, Canada). Readers scored each set of MRI 3 times, using 3 different methods including the Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity [ASspiMRI-a, grading activity (0-6) per vertebral unit in 23 units]; the Berlin modification of the ASspiMRI-a; and the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system, which scores the 6 vertebral units considered by the reader as the most abnormal, with additional scores for "depth" and "intensity." Both the order of the methods used by each reader and the timepoints (before/after treatment) were randomized. Feasibility of each scoring system was evaluated by measuring the mean time needed to score each set of MRI, and inter-reader reliability was evaluated by smallest detectable change (SDC) and by intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs separately. Sensitivity to change was investigated by calculating Guyatt's effect size on change scores. Discriminatory ability was assessed using Z-scores (Mann-Whitney test) comparing change in score between patients treated with TNF-blocking drug and placebo. RESULTS: The mean time to score one set of MRI was shortest for the Berlin method. SDC was lowest for the Berlin method and highest for SPARCC. Overall inter-reader ICC per method were between 0.49 and 0.77 for scoring activity status, and between 0.46 and 0.72 for scoring activity change. ICC for all possible reader pairs showed much more fluctuation per method, with lowest observed values of about 0.05 (very low agreement) and highest observed values over 0.90 (excellent agreement). In general, ICC for SPARCC were consistently higher than for other systems. Sensitivity to change differed per reader, and was more consistent with SPARCC than with the other methods, but was in general excellent for all 3 methods. Discrimination between groups (TNF-blocker vs placebo) assessed by Z-scores was good and comparable among methods. CONCLUSION: This experiment demonstrates the feasibility of multiple-reader MRI scoring exercises for method comparison, provides evidence for the feasibility, reliability, sensitivity to change, and discriminatory capacity of all 3 tested scoring systems to be used in assessing spinal activity on MRI in patients with AS in clinical trials. On the basis of these results it is not possible to prioritize one of the 3 methods.

A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands.

Abstract: OBJECTIVE: To determine if anti-tumor necrosis factor (TNF) therapy (adalimumab) can safely improve symptoms of erosive/inflammatory osteoarthritis (EOA). METHODS: This was an open-label pilot trial in 12 patients with EOA. Patients > 45 years old with EOA of the hands defined by > or = 2 tender and > or = 2 swollen joints (distal interphalangeal, proximal interphalangeal, first carpometacarpal) despite nonsteroidal antiinflammatory drug therapy were eligible. Patients were excluded for autoimmune arthritis, recent disease modifying antirheumatic drug use, prior use of anti-TNF therapy, infection, malignancy, or poorly controlled medical conditions. All patients received adalimumab 40 mg every other week for 12 weeks. Safety was assessed 4 weeks after the final dose. Primary endpoints included safety and American College of Rheumatology (ACR) response. RESULTS: Patients were predominantly female with a mean age of 60 years and 12 years of arthritis. All patients completed the study and safety followup. Adverse events were mild without necessitating discontinuation of study drug. After 12 weeks, there was a statistically significant improvement in the number of swollen joints compared to baseline (p

Atherosclerotic vascular events in a single large lupus cohort: prevalence and risk factors.

Abstract: OBJECTIVE: To determine prevalence and type of atherosclerotic vascular events (AVE) occurring after entry to the University of Toronto Lupus Clinic; and to compare risk factors in patients with systemic lupus erythematosus (SLE) with AVE to matched SLE controls without AVE. METHODS: Patients with SLE attending the University of Toronto Lupus Clinic who did not have AVE prior to clinic entry were included. Patients have been followed at 2-6 months since 1970 according to a standard protocol. Cases with AVE were matched for sex, era at first clinic visit (1970s, 1980s, 1990s +), inception status, age at first visit, and duration of followup. Chi-square, Fisher9s exact, paired T test, and McNemar test were used. Comparison of risk factors for the development of AVE was done using a stepwise conditional logistic regression model for matched pairs. RESULTS: In a total cohort of 1087 SLE patients followed from 1970 until 2004, the prevalence of AVE was 10.9%, and in 561 inception patients it was 9.6%. In multivariate analyses, neuropsychiatric involvement was significantly associated with AVE in both the total and inception cohorts. Smoking was also associated with AVE in the inception cohort, whereas the number of coronary artery disease (CAD) risk factors and vasculitis were significant in the total cohort. CONCLUSION: AVE are major contributors to the clinical presentation of late-stage lupus. A combination of lupus related factors and classic CAD risk factors contributed to the development of AVE.

Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis.

Abstract: 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) 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.

Tramadol for osteoarthritis: a systematic review and metaanalysis.

Abstract: OBJECTIVE: Tramadol is increasingly used for the treatment of osteoarthritis (OA) because it does not produce gastrointestinal bleeding or renal problems and does not affect articular cartilage. We sought to determine the analgesic effectiveness, the effect on physical function, the duration of benefit, and the safety of oral tramadol in people with OA. METHODS: We searched the Cochrane Central Register of Controlled Trials (Central), Medline, Embase, and Lilacs databases up to August 2005. We included randomized controlled trials (RCT) that evaluated the effect of tramadol or tramadol plus paracetamol on pain levels and/or physical function. No language restriction was applied. RESULTS: We included 11 RCT with a total of 1019 participants who received tramadol or tramadol/paracetamol and 920 participants who received placebo or active control. Participants who received tramadol reported (1) less pain [-8.5 units on a 0-100 scale; (95% CI -12.0 to -5.0)], a 12% relative decrease in pain intensity; (2) higher degree of global improvement: one of every 6 individuals taking tramadol or tramadol/paracetamol exhibited at least moderate global improvement (95% CI 4 to 9); and (3) improvement in stiffness and function, an 8.5% relative improvement in Western Ontario and McMaster University Osteoarthritis Index score, than patients who received placebo. In terms of adverse events, one of every 5 participants who received tramadol or tramadol/paracetamol experienced minor adverse events and one of every eight stopped taking the medication because of adverse events (95% CI 7 to 12) compared to participants who received placebo. CONCLUSION: Tramadol or tramadol/paracetamol decreases pain intensity, produces symptom relief, and improves function in patients with OA, but these benefits are small.