Modified Larsen Score Research Articles

Pedobarographic Measurements of Rheumatoid Feet Compared with Clinical Parameters.

Objective:This study aimed to investigate the relationship between plantar pressure pedobarographic measurements and disease activity, radiological abnormalities, and foot indexes in patients with rheumatoid arthritis (RA).Methods:Sociodemographics, foot symptoms, anatomical distribution, pain intensity and duration, and podiatry services access data were collected. Disease activity scale of 28 joints (DAS28) was used for the disease activity, and Health Assessment Questionnaire (HAQ) was used for the functional status. Foot function index (FFI) was used to measure the impact of foot pathology on its function. The Modified Larsen scoring was used to assess radiological abnormalities. Pedobarographic measurements were used to analyze foot loading characteristics.Results:A total of 104 feet of 52 patients with RA was evaluated. DAS28 scores did not correlate with the plantar pressure values (p>0.05). A significant correlation was found between HAQ scores and right medial midfoot loading pressure (r=0.355; p<0.01). FFI scores were positively correlated with right lateral midfoot loading pressure (r=0.302; p<0.05). No relationship was found between Manchester Foot Pain and Disability Index and plantar loading characteristics. The radiological scores were correlated with left lateral hindfoot plantar pressure (r=0.286; p<0.05).Conclusions:Pedobarographic measurements can be considered as a follow-up evaluation tool for the evaluation of all foot parts (forefoot, midfoot, and hindfoot). Rheumatoid feet investigation showed that foot involvement is independent of the disease duration, whereas midfoot plantar pressures are associated with the body mass index. Additionally, DAS28 may fall short as a marker of disease activity because it neglects foot problems.

The relationship of serum calprotectin with disease activity, functional status, ultrasonographic findings and radiological damage in rheumatoid arthritis patients

Aim of the workTo measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) patients and to assess its association with disease activity, functional status, ultrasonographic findings, and radiological damage. Patients and methodsThis study included 47 RA patients and 33 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score (DAS28), health assessment questionnaire (HAQ), modified Larsen radiological score, musculoskeletal ultrasound and serum CLP levels were assessed. ResultsThe mean age of the patients was 42.5 ± 12.8 years; 34 females and 13 males (F:M 2.6:1) with a mean disease duration of 2.6 ± 1.1 years. RF was positive in 72%. CLP level was significantly increased in patients compared to control (2.78 ± 0.89 μg/ml vs. 0.84 ± 0.5 μg/ml; p < 0.001) and in those with activity (3.27 ± 0.75 μg/ml) compared to those in remission (1.92 ± 0.15 μg/ml). A significant correlation was detected between CLP and DAS28, ESR, CRP, HAQ, and modified Larsen scores (p < 0.001). On regression, tender and swollen joint counts, ESR, CRP, HAQ, modified Larsen, ultrasound 7 score and CLP level were significant predictors of activity but were insignificant on multivariate analysis. At a cut-off value of 2.35 μg /ml CLP can significantly differentiate active RA patients from those in remission (AUC 0.95; p < 0.001) at a sensitivity of 90%, specificity of 100%, and accuracy of 95%. ConclusionThe serum CLP levels were significantly high in RA patients and these high levels were associated with disease activity, functional status, ultrasonographic findings, and radiological damage.

Clinical significance of serum survivin in rheumatoid arthritis patients: Relation to disease activity, functional status and radiological damage

Aim of the workTo measure the levels of serum survivin in rheumatoid arthritis (RA) patients and to assess its relation to disease activity, functional impairment, and radiological damage. Patients and methodsThis study included 58 RA patients and 34 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), modified Larsen radiological score and serum survivin level were assessed. ResultsThe mean age of the patients was 43.5 ± 11.5 years; 43 females and 15 males (F:M 2.9:1) with a mean disease duration of 2.6 ± 1.13 years. RF was positive in 79% Survivin level was significantly increased in patients compared to the controls (171.8 ± 74.4 pg/ml vs. 98.7 ± 16 pg/ml, p < 0.001) and in those with activity (203.1 ± 69.1 pg/ml) compared to those in remission (102.1 ± 12.1 pg/ml). Survivin level tended to be higher in females (177.1 ± 79.5 pg/ml) compared to males (156.4 ± 57 pg/ml) (p = 0.36) and was significantly higher in those with positive RF (183 ± 75.9 pg/ml) compared to those with a negative test (128.6 ± 50.5 pg/ml) (p = 0.02). A significant correlation was detected between survivin and disease duration, DAS28, ESR, CRP, VAS, HAQ, RF, and modified Larsen scores (p < 0.001). On univariate logistic regression the RF, HAQ, modified Larsen and survivin level were significant predictors but were insignificant on multivariate analysis. ConclusionIn RA patients the serum survivin is significantly increased compared to the controls. The disease activity, functional impairment, and radiological joint damage were associated with these high concentrations.

Clinical correlation and determination of Dkk-1 and sclerostin levels in patients with rheumatoid arthritis

The aim of this study is to compare serum Sclerostin and Dickkopf-1 (Dkk-1) levels in patients with rheumatoid artrithis (RA) and healty controls to determine their clinical significance in patients with RA. Sixty with RA according to American Collage of Rhematology criteria and at least one year follow up, enrolled in this study and compared thýrty healty controls. To evaluate disease activity score 28 (DAS28) was calculated. Physical function capasity (disability) was asssessed with Health Assesment Quastionnarie (HAQ) and Nottingham Health Profile (NHP). Erythrocyte Sedimentation Rate, C Reactive Protein, Rheumatoid Factor and anticyclic citrullinated peptide levels were determined by routine laboratory methods. Serum sclerostin and Dkk-1 levels of the patients with RA and healty controls were measured by ELISA. Radiographic assesment of hands joints was evaluated according to the modified Larsen score. Between patients with RA and healty controls, there was significant difference with respect to the age (respectively p=0.00) and significant difference with respect to gender (p=0.033). Serum sclerostin and dickkopf-1 levels were significantly higher (p=0.002, p=0.049) in patients with RA compared to healty controls. Serum sclerostin and dickkopf-1 levels were doesnt correlated with clinical and laboratory parameters of disease activity. There was no significant correlation between radiological scoring of joint damage and serum sclerostin and dickkopf-1levels (p 0.05). This study shows that Serum sclerostin and dickkopf-1 levels were increased in RA patients in comparison to control group but there was no significant correlation with the disease activity and joint damage. The sample of our study can be enlarged and further studies are required.

Genetic associations with radiological damage in rheumatoid arthritis: Meta-analysis of seven genome-wide association studies of 2,775 cases.

BackgroundPrevious studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants.MethodsSeven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases.ResultsIn the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10-8). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10-6). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P<5x10-6; in the European primary and secondary analyses 13 and 10 regions contained SNPs reaching P<5x10-6, respectively. Of the previously validated SNPs for radiological progression, only rs660895 (tagging HLA-DRB1*04:01) attained significance (P = 1.6x10-5) and had a consistent direction of effect across GWAS.ConclusionsOur meta-analysis confirms the known association between the HLA-DRB1 shared epitope and RA radiological damage. The lack of replication of previously validated non-HLA markers highlights a requirement for further research to deliver clinically-useful prognostic genetic markers.

Matrix metalloproteinase-3 levels in relation to disease activity and radiological progression in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory and systemic disease of unknown etiology that primarily affects synovial joints and involves progressive destruction around the joints. Inflammation starting in the joint synovium causes the destruction of cartilage, bone and other adjacent tissues with pannus formation. The aim of this study was to evaluate serum matrix metalloproteinase-3 (MMP-3) levels and their clinical and radiological significance in patients with rheumatoid arthritis. The study included 59 patients with RA and 30 healthy controls. Serum MMP-3 levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Patients with a Disease Activity Score 28 (DAS28) ≤3.2 were categorized as having lower disease activity, while a DAS28 score >3.2 indicated patients with moderate/high disease activity. Additionally, the patients were divided into 2 groups in terms of disease duration: early RA (disease duration ≤2 years) and established RA (disease duration ≥2 years). Functional disability was evaluated using the Health Assessment Questionnaire (HAQ) and Nottingham Health Profile (NHP). Radiographs were scored using modified Larsen scoring. Serum MMP-3 levels in patients with RA were significantly higher than in controls (p = 0.001). Serum MMP-3 levels were correlated with laboratory and clinical parameters of disease activity, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), DAS28, and HAQ score; the exceptions were rheumatoid factor (RF) and cyclic citrullinated peptides (CCP). The serum MMP-3 levels of RA patients with moderate/high disease activity were found to be significantly higher than those of the patients with low disease activity (p < 0.001). However, MMP-3 levels were found to be similar in both established and early RA patients (p = 0.927). Additionally, the modified Larsen scores, which indicate structural damage, correlated significantly with serum MMP-3 levels (p = 0.001). These results indicate that serum MMP-3 levels may be used as an indicator for structural damage such as erosions in the early stages of the disease, and to monitor disease activity.

Serum Level of Endothelial Cell-Specific Molecule -1 (ESM -1) as a New Potential Biomarker for Rheumatoid Arthritis Disease Activity

Background:Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by destruction of the joint cartilage and bone. Endothelial dysfunction (ED) in RA may be related to disease activity. Our objective is to explore serum levels of endothelial cell-specific molecule-1 (ESM-1) as a biomarker for RA disease activity.Methods:A cross-sectional study was carried out and included 83 adult patients with RA, in addition to 20 healthy subjects (age and sex-matched) as a control group. Based on Disease Activity Score in 28 joints (DAS-28), the patient's group was subdivided into four subgroups(remission, mild, moderate and severe disease activity state). The demographic &amp; clinical data, BMI, DAS-28 and Serological assessment [Erythrocyte Sedimentation Rate (ESR), CRP, Rheumatoid Factor (RF) and Anti-Citrullinated Peptide Antibody (ACPA)] were recorded. ESM-1was assayed for all participants.Results:Serum levels of ESM1 were significantly higher in the patient group than the control group (P&lt; 0.0001). ESM-1 serum levels were significantly higher in patients with severe disease activity subgroup compared with patients with remission and mild disease activity subgroups (P&lt; 0.0001). ESM-1 was positively and significantly correlated with DAS-28 score, The Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Larsen score (P= 0.002, 0.0001 &amp; 0.0001 respectively).Conclusion:ESM-1 could be a biomarker for RA disease activity.

Study of interleukin 33 in rheumatoid arthritis versus osteoarthritis patients

Aim of the workTo compare the expression of serum interleukin 33 (IL33), a new member of the interleukin1 (IL-1) cytokine family, in rheumatoid arthritis (RA) versus osteoarthritis (OA) patients and to correlate it with clinical, laboratory and radiographic parameters.Subjects and methods20 RA and 20 primary knee OA patients. The levels of serum IL-33 were measured by enzyme-linked immunosorbent assay (ELISA) while anticyclic citrullinated peptide (Anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured by standard laboratory techniques. Plain x-ray of both hands and wrists were evaluated using the modified Larsen score 1995 (MLS) in RA patients. Knee OA grading was performed according to the Kellgren Lawrence classification. The correlation of IL-33 level with clinical, laboratory and radiological data of RA and OA was analyzed.ResultsSerum IL-33 level was significantly higher in RA than in OA patients (P< 0.001). This level was positively correlated with disease duration, clinical and laboratory markers of disease activity, impaired functional status and radiographic severity in RA while not in OA patients.ConclusionsThese findings support that IL-33 could have an essential proinflammatory role in the pathogenesis of RA and that IL-33 level may be a monitor of disease activity and severity. IL-33 may become therapeutic target for RA.

Relationship Between Leptin and Neopterin Levels and Disease Activation Parameters in Patients With Rheumatoid Arthritis.

This study aims to determine serum leptin and neopterin levels in patients with rheumatoid arthritis (RA) and investigate the relationship between clinical and laboratory parameters of disease activity and radiographic progression. The study included 33 RA patients (9 males, 24 females; mean age 52.5±12.3 years; range 29 to 75 years) and age- and sex-matched 24 healthy controls (11 males, 13 females, mean age 42.5±14.8; range 18 to 75). RA patients were divided into three groups based on Disease Activity Scores in 28 joints (DAS28) as low disease activity, moderate disease activity, and high disease activity groups. Of the patients, 13 (39.4%) had low disease activity (DAS28=2.6-3.2), 12 (36.4%) had moderate disease activity (DAS28=3.2-5.1), and eight (24.2%) had high disease activity (DAS28≥5.1). Mean serum leptin and neopterin levels in the RA group were 23.98±18.88 ng/mL and 1.88±1.84 nmol/L, respectively. Mean serum leptin and neopterin levels in the control group were 19.40±13:42 ng/mL and 1.13±0.55 nmol/L, respectively. There was no statistically significant difference in the levels of serum leptin (p=0.674) and neopterin (p=0.078) between RA patients and control group. Serum leptin (p=0.574) and neopterin (p=0.921) levels in RA patients and control group showed no correlation with body mass index levels. Besides, there was no correlation between age and plasma leptin and neopterin levels and rheumatoid factor positivity, anti-cyclic citrullinated peptide antibodies, disease duration, erythrocyte sedimentation rate, and C-reactive protein levels in RA group. In RA patients, there was no correlation between serum leptin and neopterin levels and clinical and laboratory parameters indicating the disease activity. In RA patients, there was also no correlation between radiographic joint damage and serum leptin and neopterin levels. A positive correlation was shown in RA patients between disease duration and modified Larsen score (p=0.01). In our study, no correlation was detected between serum leptin and neopterin levels and disease activity parameters in RA patients. Therefore, leptin and neopterin levels may not be considered as beneficial inflammation parameters to be used in the diagnosis of RA and disease activation tracking.

Is 4-Hydroxynonenal a Predictive Parameter for the Development of Joint Erosion in Patients With Rheumatoid Arthritis?

This study aims to evaluate serum 4-hydroxynonenal (4-HNE) levels and its clinical and radiological significance in patients with rheumatoid arthritis (RA). The study included 40 patients (8 males, 32 females; mean age 51.4±11.2 years; range 24 to 72 years) with RA and 30 healthy controls (8 males, 32 females; mean age 53.0±11.7 years; range 24 to 72 years. Serum 4-HNE levels were measured using sandwich enzyme-linked immunosorbent assay method. Patients with disease activity score 28 ≤3.2 and >3.2 were allocated into low and high/moderate disease activity groups, respectively. Additionally, patients were divided into two groups as early RA (disease duration ≤2 years) and established RA (disease duration ≥2 years). Functional disability was evaluated using health assessment questionnaire. Radiographs were scored using the modified Larsen scoring. Serum 4-HNE levels in patients with RA were significantly higher than controls (p=0.001). Serum 4-HNE levels did not correlate with laboratory or clinical parameters of disease activity including erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, and health assessment questionnaire. Serum 4-HNE levels were higher in patients with established RA than patients with early RA (r=0.487, p=0.001). Besides, modified Larsen score which indicates structural damage correlated significantly with serum 4-HNE levels (p=0.001). These results indicate that serum 4-HNE levels may be used as an indicator for structural damage such as erosions in the early stage of RA; however, they are not efficient to monitor disease activity.

Digital X-ray radiogrammetry and its sensitivity and specificity for the identification of rheumatoid arthritis-related cortical hand bone loss.

Digital X-ray radiogrammetry (DXR) is a computer-assisted diagnosis technique for quantifying cortical hand bone mineral density (BMD) as well as the metacarpal index (MCI) in the metacarpal bones from radiographs. The objective was to compare DXR-BMD and DXR-MCI between healthy individuals and patients with rheumatoid arthritis (RA) and verify the sensitivity and specificity of this technique for the identification of cortical hand bone loss as an additional diagnostic approach in RA. 618 patients were enrolled and divided into two groups: those with RA (n=309) and a healthy control group (n=309) as a reference database. DXR-BMD and the DXR-MCI were measured by DXR using hand radiographs. The severity of RA was evaluated by the modified Larsen score. Mean values for DXR-BMD and DXR-MCI in RA patients were significantly lower compared to healthy subjects (-20.7 and -21.1%, respectively). Depending on the severity of RA-related joint damage, DXR-BMD revealed a significant reduction of -28.1% and DXR-MCI -28.2%, comparing score 1 and score 5 of the modified Larsen score. Both DXR-BMD and DXR-MCI had a high sensitivity (DXR-BMD 91%, DXR-MCI 87%) and a moderate specificity (DXR-BMD 47%, DXR-MCI 49%) to identify RA-related cortical hand bone loss. The DXR technique seems to be able to quantify RA-related periarticular bone loss as a characteristic feature in the course of RA. Consequently, periarticular osteoporosis seems to function as a reliable diagnostic approach comparable to erosions and joint space narrowing in the diagnosis of RA and as a surrogate marker for the progression of bone loss in RA.

Oligomeres Knorpelmatrixprotein in Serum und Synovialflüssigkeit – Konzentrationen bei früher und etablierter rheumatoider Arthritis

To assess cartilage oligomeric matrix protein (COMP) levels in serum and synovial fluid in patients with early and established rheumatoid arthritis (RA), and to correlate the levels with clinical, laboratory and radiological characteristics. The study included 24female RA patients. Full medical history was taken, thorough clinical examination and laboratory investigations performed, and body mass index (BMI) recorded. Radiological damage was assessed according to the modified Larsen score. Disease activity score28 (DAS28) was calculated. The control group comprised 30age- and gender-matched healthy subjects. Serum and synovial COMP levels were determined by enzyme-linked immunosorbent assay (ELISA). Mean patient age was 44.04 ± 10.5years. Of the 24patients, 12had early RA and 12had established disease with joint destruction; 5of each group had knee effusion. Serum COMP was significantly higher in patients (19.54 ± 5.47µg/ml) compared to controls (5.93 ± 1.95µg/ml; p < 0.001) and was also significantly higher in patients with established disease (23.9 ± 3.1µg/ml) compared to those in early stages (15.1 ± 3.2µg/ml; p < 0.001). Synovial COMP was also significantly increased in established compared to early-stage RA (31.2 ± 9.8µg/ml vs. 51.6 ± 10.4µg/ml; p = 0.013). Serum and synovial COMP significantly correlated with age, disease duration, BMI, DAS28 and modified Larsen score. On performing regression analysis in RA patients, only BMI could predict the serum level of COMP (p = 0.02). COMP is a promising biomarker for disease activity in RA, making it a potential therapeutic target. The obvious correlation with the BMI throws light on the importance of weight control not only in osteoarthritis (OA), but also in RA.

Association of Anti-cyclic Citrullinated Peptide Antibodies with Clinical and Radiological Disease Severity in Rheumatoid Arthritis

This study assessed an association of anti-cyclic citrullinated peptide antibodies (ACPA) with clinical and radiological disease severity in patients with rheumatoid arthritis (RA). Fifty patients diagnosed with RA as per 2010 revised American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria were included in this cross-sectional study. Serum levels of ACPA, C-reactive protein (CRP) and rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), disease activity score with 28-joint counts and ESR (DAS28-ESR), patient's global assessment of disease activity using visual analogue scale (PtGA-VAS), modified health assessment questionnaire score (M-HAQ) and radiological damage in hands and feet (modified Larsen score) were determined. ACPA were positive in 48 (96%) and RF in 44 (88%) patients. Mean Larsen score was 19.82 ± 17.11 and mean DAS28-ESR 6.39 ± 1.59. A significant correlation of ACPA levels was seen with RF (p=0.03) and Larsen score (p=0.02) but not with DAS28-ESR (p=0.17) and M-HAQ (p=0.81). A significant correlation was seen between Larsen score and disease duration (p<0.0001), age (p=0.04), DAS28-ESR (p=0.001) and M-HAQ (p<0.0001). Multivariate analysis showed that painful joint count (p=0.003), ESR (p<0.001) and PtGA-VAS (p=0.009) were independently associated with clinical disease activity severity. Disease duration (p=0.01), ACPA levels (p=0.004) and DAS28-ESR (p=0.03) were independently associated with radiological joint damage. Serum ACPA levels correlate significantly with radiological severity of RA but not with clinical disease severity and are independently associated with radiological outcome.

Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome.

To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity. The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS-28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25-OH-vitamin D was measured in patients and controls. The patients' mean age was 41.59±9.69years and disease duration 5.89±3.67years. The level of vitamin D in RA patients was significantly lower (23.11±12.71ng/mL) than that in the controls (32.59±13.06ng/mL) (P=0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n=33) had significantly lower levels of vitamin D (19.08±10.59ng/mL) than those without (27.55±13.51ng/mL) (P=0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39±7.84ng/mL) to those not (31.85±13.85ng/mL) (P<0.001). Vitamin D significantly correlated with QoL index (r=0.58, P<0.001) and negatively with HAQ II (r=-0.36, P=0.004) and BMI (r=-0.39, P=0.001). Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium.

AB0147 Role of Sclerostin in Rheumatoid Arthritis: New Insights

BackgroundRheumatoid arthritis (RA) is an autoimmune-inflammatory disease that may lead to joint destruction and disability Several key molecules are involved in the regulation of osteoclast differentiation, which are induced upon...

AB0006 Genetic Susceptibility Variants for Rheumatoid Arthritis do not Associate with Radiological Progression in Early Active Disease

BackgroundSeveral studies have tested the hypothesis that RA susceptibility variants associate with radiological progression. Their findings are often not replicated; additionally they have examined only a proportion of risk loci...

Allele‐Dose Association of the C5orf30 rs26232 Variant With Joint Damage in Rheumatoid Arthritis

There is increasing evidence to indicate that genetic factors contribute significantly to radiologic joint damage in rheumatoid arthritis (RA). The aim of the present study was to determine whether genotypes of 10 recently identified RA susceptibility loci are associated with radiologic severity. A 2-stage study was performed using 3 Northern European RA populations: a British cross-sectional population (discovery cohort; n=885) and the Leiden Early Arthritis Clinic (EAC) cohort (n=581) and Yorkshire Early Arthritis Register (YEAR) cohort (n=418) (validation cohorts). Radiologic damage was assessed using a modified Larsen method for scoring radiographs (in the discovery cohort) or modified Sharp/van der Heijde score (in the 2 validation cohorts). A meta-analysis was performed to bring together the evidence from the 3 studies, using data on radiologic severity of joint damage from a single time point. An allele-dose association of rs26232 was present in the discovery population (P=4×10(-4)); the median modified Larsen scores of radiologic joint damage per genotype were 31 (for those with CC), 27 (for those with CT), and 16 (for those with TT). The allele-dose association of rs26232 was replicated in both the Leiden EAC cohort during the initial 7 years of RA (P=0.04) and the YEAR cohort (P=0.039). In a fixed-effects meta-analysis of all 3 studies, the per T allele effect on the ratio of radiologic severity scores was 0.90 (95% confidence interval 0.84, 0.96; P=0.004). The variant rs26232, in the first intron of the C5orf30 locus, is associated with the severity of radiologic damage in RA and is independent of established prognostic biomarkers. The biologic activities of C5orf30 are unknown, but our genetic data suggest that it is involved in mediating joint damage in RA.

Radiologic analysis of the effect of tocilizumab on hands and large joints in children with systemic juvenile idiopathic arthritis

Objectives To assess the efficacy of tocilizumab for preventing damage to the joints of systemic juvenile idiopathic arthritis (sJIA) patients, we examined serial radiographs of the hands and large weight-bearing joints of these patients before and after treatment with this agent.Methods Nine patients with sJIA receiving 8 mg/kg of tocilizumab intravenously every 2 weeks were studied. The mean follow-up period was 82 months. The number of active joints and laboratory markers of inflammation were assessed before and after tocilizumab treatment, together with radiologic evaluation of the hips, knees, ankles, shoulders, and elbows. The latter examination included soft tissue swelling, juxta-articular osteoporosis, epiphyseal irregularity, joint-space narrowing, cyst formation, erosion, and localized growth abnormalities. Modified Larsen scores for the large joints and the Poznanski score were also recorded.Results After tocilizumab treatment, the number of active joints and serum inflammatory markers decreased (p < 0.01). There was a decrease in radiologic abnormalities at the final follow-up (p < 0.01) with the exception of localized growth abnormalities. Radiologic improvement was observed in 47 joints (52 %), but ten (11 %) worsened. Total Larsen score was decreased from 15.8 to 10.9 at the final follow-up. Although the Poznanski score did not change after tocilizumab treatment, it was closely correlated with the total Larsen score (r = 0.53, p < 0.05).Conclusions We describe radiologic improvement of the majority of damaged large joints in sJIA following tocilizumab therapy, but some deteriorated further despite stabilization of systemic inflammatory responses. Further studies with a larger number of patients are needed.

AB0852-HPR Pedobagraphic measurements of rheumatoid feet and comparison with clinical parameters

BackgroundFoot involvement in rheumatoid arthritis (RA) have been reported to be 56-100% in different studies. Pedobarography is used for dynamic plantar pressure measurement and to point out deformities of rheumatoid...

FRI0022 Relationships between radiographic damage, shared epitope alleles and circulating cytokines in dmard-naïve early ra patients

BackgroundAlthough therapeutic targeting of humoral and cellular inflammatory biomarkers has improved outcomes in subsets of patients with severe RA, the identification of novel targets based on insights into disease immunopathogenesis...