A. Kleyer

Diabetes Is an Independent Predictor for Severe Osteoarthritis: Results from a longitudinal cohort study

OBJECTIVE To evaluate if type 2 diabetes is an independent risk predictor for severe osteoarthritis (OA). RESEARCH DESIGN AND METHODS Population-based cohort study with an age- and sex-stratified random sample of 927 men and women aged 40–80 years and followed over 20 years (1990–2010). RESULTS Rates of arthroplasty (95% CI) were 17.7 (9.4–30.2) per 1,000 person-years in patients with type 2 diabetes and 5.3 (4.1–6.6) per 1,000 person-years in those without (P < 0.001). Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard ratios (95% CI), 3.8 (2.1–6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1–3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA. The probability of arthroplasty increased with disease duration of type 2 diabetes and applied to men and women, as well as subgroups according to age and BMI. Our findings were corroborated in cross-sectional evaluation by more severe clinical symptoms of OA and structural joint changes in subjects with type 2 diabetes compared with those without type 2 diabetes. CONCLUSIONS Type 2 diabetes predicts the development of severe OA independent of age and BMI. Our findings strengthen the concept of a strong metabolic component in the pathogenesis of OA.

SAT0283 High Incidence of Flare After Discontinuation of Disease Modifying Anti-Rheumatic Drugs in Patients with Psoriatic Arthritis

Background In the era of modern anti-rheumatic therapy, it is now possible to contemplate the idea of clinical remission in patients with psoriatic arthritis (PsA)1. It is however unknown whether patients in clinical remission can stop methotrexate (MTX) or tumor necrosis factor inhibitor (TNFi) treatment2. Objectives To investigate drug-free remission in patients with PsA and potential predictors for flare. Methods Patients with PsA in remission (no musculoskeletal symptoms, no or minimal skin/nail disease) for at least 6 months were included. At baseline the following parameters were assessed: age, sex, BMI, disease duration, duration of remission, swollen joint count, tender joint count, VAS-pain, VAS-global, NAPSI, PASI, MASES, LDI, HAQ-DI, SF-36, FACIT-F, anti-rheumatic therapy (MTX, TNFi), ESR and CRP. In addition, ultrasound of 20 joints and 20 enthesis was performed. After discontinuation of therapy at day 1, patients were followed for 6 months for the occurrence of flares. Results 26 patients (20 males, 6 females) were enrolled. Mean ± SD age was 55 ± 14 years, mean ± SD disease duration was 6.1 ± 6.2 years, mean ± SD duration of remission was 23.9 ± 23.7 months. 15 patients received MTX monotherapy, 11 were treated with TNFi (6 in combination with MTX). We observed a high incidence of flares (76.9%, N= 20), with flares occurring relatively early (74.50 ± 50.79 days). There was no difference in flare rates between the MTX and TNFi groups. Due to our low number of patients, predictors of flare could not be determined but some important trends were observed. Male patients were more likely to flare (OR=18.00; [95%CI: 1.92-168.99]; p=0.011); patients with lower BMI (U=33.50, z=-1.61, p=0.107, r=0.32) and longer disease duration (U=35.50, z=-1.51, p=0.132, r=0.30) showed medium effect trends to flare. Further, presence of calcifications at the enthesial sites was associated with flares (U=33.50, z=-1.50, p=0.133, r=0.30). Conclusions This study showed a high incidence of flare in patients with PsA after discontinuing therapy. Although remission in PsA is an obtainable goal, drug-free remission may not be realistic for the majority of patients. Our study suggests that some baseline characteristics, such as male sex, low BMI, longer disease duration and enthesial calcifications predict flares of PsA after discontinuation of anti-rheumatic therapy. References Kavanaugh A., Fransen J., Defining remission in psoriatic arthritis. Clin Exp Rheumatol 2006: 24(Suppl. 43): S83-S87. Saber TP, et al., Remission in psoriatic arthritis: is it possible and how can it be predicted? Arthritis Research & Therapy 2010, 12:R94. Disclosure of Interest None Declared

Does subclinical inflammation contribute to impairment of function of knee joints in aged individuals? High prevalence of ultrasound inflammatory findings

OBJECTIVES To investigate the prevalence of knee US findings of inflammation and structural damage in aged individuals (≥60 years) of a long-term population-based cohort and to correlate these findings with demographic, clinical and laboratory parameters. METHODS Cross-sectional clinical and US investigation of both knee joints during the 2010 follow-up of the prospective population-based Bruneck Study. Demographic variables, physical activity, comorbidities, medications, pain, and functional scales related to the knee joints were recorded. US-assessed parameters were synovial hypertrophy, power Doppler signal, joint effusion, cartilage abnormalities, osteophytes, enthesopathy and bursitis. Statistics included univariate and multivariate regression analysis. RESULTS A total of 488 subjects (mean age 72.5 years; 53.5% females, 46.5% males) were examined by clinical assessment, and 433 of these underwent US examination of both knees. Both inflammatory and structural abnormalities were found in 296 (68.8%) subjects. Inflammatory abnormalities were significantly associated with age in years, male gender, diabetes and the presence of knee joint symptoms. In the multivariate analysis, age, male gender and knee swelling emerged as independent predictors of inflammation [odds ratio (OR) (95% CI) = 1.06 (1.03, 1.09), 2.55 (1.55, 4.21) and 5.92 (1.99, 17.58), respectively]. CONCLUSION The present study showed a high prevalence of US inflammatory abnormalities in the knee joints of a normal aged population. These data suggest a substantial contribution of inflammation in progressive impairment of joint function with age.

FRI0625 Improvement of joint inflammation as assessed by MRI and power doppler ultrasound (PDUS) in an open label study in patients with active psoriatic arthritis treated with secukinumab (PSARTROS)

Background Secukinumab, an anti-interleukin 17A monoclonal antibody, showed significant improvement of signs and symptoms of psoriatic arthritis (PsA) in FUTURE 1 study. Available studies used conventional radiography, not allowing a deeper imaging analysis of the inflammatory changes during application. Objectives To assess short term efficacy of secukinumab on inflammation and structural damage according to change in OMERACT-EULAR ultrasound score and the MRI PsAMRIS score in PsA patients. Methods PsA patients with active disease (TJC and SJC ≥3), were included in the 24 week open label prospective PSARTROS study and treated with subcutaneous secukinumab 300 mg once weekly over 4 weeks, then once every 4 weeks. Baseline 1,5T MRI hand scans and ultrasound imaging of 28 joints were performed at baseline and after 24 weeks of treatment. MRI was scored according to PsAMRIS, ultrasound for synovial hypertrophy and Doppler activity according to OMERACT scores. Statistical significance was set at p≤0.05. Results 20 patients, mean age 52±9.9 years, 60% female, mean disease duration 6.7±5.9 years, 50% naïve for biological therapy, were included in the study. Three patients were early discontinued (recurrent pharyngitis, lack of efficacy, withdrawal of consent), and were not included into the longitudinal analysis. Baseline DAS28 was 5.03±0.96, baseline DAPSA was 32.2±12. 1. On baseline MRI, all patients had at least one inflammatory sign (synovitis: 90%, osteitis: 20%, periarticular inflammation: 25%, flexor tenosynovitis: 35%, bone proliferation: 30%, erosions: 60%). Baseline composite PsAMRIS score was 11.6±12.8 and baseline PsAMRIS synovitis score was 3.7±3.3. Baseline ultrasound synovial hypertrophy and Doppler activity were 6.2±4.5 and 3.5±4.0, respectively. Specific MRI and ultrasound scores were significantly correlated with DAS28 and DAPSA at baseline. Clinical disease activity parameters significantly improved at follow up (DAS28: 2.94±0.95, p<0.001; DAPSA: 8.8±5.8, p<0.001). PsAMRIS synovitis score (2.5±2.4) as well as composite PsAMRIS score (8.8±10.0) decreased longitudinally with secukinumab treatment (p=0.034 and p=0.039, respectively). There was no progression in erosion or proliferation scores between baseline and follow-up. Synovial hypertrophy and Doppler activity in ultrasound also significantly improved with secukinumab treatment (2.3±3.5; p=0.009 and 1.8±2.7; p=0.003, respectively). A significant percentage of patients reaching minimal disease activity showed residual signs of synovitis in the MRI and US (66% and 50%, respectively). Conclusions Secukinumab significantly improves MRI and ultrasound signs of joint inflammation in patients with PsA. Acknowledgements This study was supported by an unrestricted grant from Novartis. Disclosure of Interest None declared

SAT0192 In Vivo Detection of Cortical Micro Channels in Metacarpophalangeal Joints with Xtreme-Ct - A New Instrument to Visualize Communication between the Bone Marrow and the Joint Space

Background Synovitis and osteitis are distinct pathologic findings in patients with rheumatoid arthritis (RA). Their frequent simultaneous occurrence led to the theory of increased communication between the bone marrow and synovial compartments. A widening of pre-existing cortical bone channels, which carry microvessels and penetrate the cortical barrier, has been previously described in animal models as a result of increased osteoclast-mediated bone resorption. To our knowledge these communication channels have not been clearly visualized in humans in vivo. Objectives We hypothesised that it is possible to detect cortical channels in human RA patients by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods We used HR-pQCT (XtremeCT, Scanco Medical, Switzerland) with a resolution as low as 82 microns in voxel size to scan the metacarpophalangeal (MCP) joint 2 of 10 patients with early RA (ACPA positive, mean age 36.2±8.2 years, mean disease duration 1.2±0.8 years, 50% female) without concurrent bone erosions and 10 healthy controls of comparable age (mean age 37.9±7.6 years, 70% female). Images were downsized to the minimum of one slice with the 3D evaluation program provided by the manufacturer. Transversal (Figure 1), coronal and sagittal images were obtained using the subdim feature of the 3D evaluation program. Transversal planes were projected at the proximal insertion of the capsule of MCP2 head. Sagittal and coronal planes were set exactly into the middle of the MCP2 head. Results Cortical bone channels can be clearly visualized with this technique, which mimics a virtual histopathologic slide of the joint (Figure 1). In the transversal view cortical discontinuations (arrows) were observed more frequently (p=0.05) in RA patients (Fig. 1B) compared to healthy controls (Fig. 1A). Due to the small sample size, statistical analysis of the coronal and sagittal view were not performed, though especially in the sagittal view a trend of more cortical bone channels in RA was detected (4.6±3.5 vs.2.3±1.9). Conclusions In summary, we show that in vivo visualization of cortical bone channels in humans is feasible and that early RA patients exhibit a significantly higher number of such channels in the area of the proximal insertion site of the capsule compared to controls. These changes may represent key communication pathways between the bone marrow and the joint and the place where inflammation starts in RA patients. These changes cannot be seen by conventional X-ray or MRI. Systematic evaluation of cortical bone channels will be necessary to define the extent of these lesions in inflammatory joint diseases as well as their longitudinal dynamics in larger cohorts. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4395

SAT0182 Magnetic Resonance Imaging (MRI) of Hands of Psoriasis Patients: High Incidence of Inflammation

Background Patients with cutaneous psoriasis (PSO) are at risk of developing psoriatic arthritis (PsA) overtime. The transition from skin disease to joint involvement is only partially characterized. Advanced imaging can depict signs of subclinical joint involvement. Objectives To assess the prevalence of inflammatory MRI signs in a group of PSO patients with no history or presence of PsA, who showed bony changes (either erosions or osteophytes) on high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondly, to examine whether inflammation on MRI is linked to the changes on HR-pQCT. Methods PSO patients (with no arthritis, enthesitis nor dactylitis) underwent HR-pQCT and 1.5T magnetic resonance imaging (MRI) of the dominant hand. HR-pQCT scanning was conducted on the metacarpophalangeal (MCP) joints 2 and 3. Images were analyzed for the presence of periarticular changes as erosions and osteophytes. MRI images were acquired for the whole hand. Subsequent analysis of the images focused on the detection of osteitis, synovitis, tenosynovitis of the flexor tendon, periarticular inflammation at the MCP, PIP and DIP region of the 2nd to 5th finger, according to the definitions of key pathologies provided for the PsAMRIS scoring system.1 HR-pQCT and MRI images have been analyzed by 2 independent readers, mean time interval between both imaging techniques was 42 days. The study was conducted upon approval by the local ethic committee and the National Radiation Safety Agency (BfS). Patients participated after signing informed consent. Results Images were acquired from 55 PSO patients (36.4% female) of mean age 49.5±11.5 years, mean disease duration 15.2±15.4 years and mean PASI score of 6.2±8.0. The most prevalent subtype was psoriasis vulgaris (73%), while nail psoriasis was present in 51% and scalp involvement in 29%. By HR-pQCT, 29% of the patients showed erosions, while all presented osteophytes. Of the 55 patients, 26 (47%) showed at least one of the mentioned inflammatory signs on MRI. In detail, osteitis was found in 6 out of the 55 patients (11%), while synovitis in 21 (38%); tenosynovitis and periarticular inflammation were detected each in 2 patients (4%). In the total sample, partial correlations (controlling for the influence of age and disease duration) between bony changes in HR-pQCT and osteitis as well as synovitis in MRI did not show any significant relations. Conclusions Subclinical inflammatory lesions are prevalent in the joints of patients with PSO and affect about half of the patients. These findings suggest that a substantial proportion of PSO patients are affected by joint inflammation but are not classified as PsA. Interestingly, the relation of inflammatory-MRI changes to structural-CT changes in the joints of PSO patients is rather poor at the cross-sectional level, which will necessitate longitudinal assessment of joint inflammation in PSO patients. References Ostergaard M et al, J Rheumatol. 2009 Aug; 36(8): 1816-24 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5412

FRI0559 Biomechanical properties of radial bone are different between auto-antibody positive and negative rheumatoid arthritis

Background Functional properties of bone in rheumatoid arthritis (RA) are still not well characterised. Objectives This study aimed to define the impact of anti-citrullinated antibodies (ACPA) on biomechanical properties in RA. Methods Based on on high-resolution peripheral quantitative computed tomography (HR-pQCT) data from the distal radius of ACPA-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC) micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone.(1 Comparisons of µFEA parameters between groups was calculated and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength. Results A total of 276 subjects (96 RA+, 84 RA- and 96 HC) were analysed. Age and sex distributions were not significantly different between the three groups. In RA +but not in RA- failure load and stiffness were significantly decreased compared to HC (both p<0.001). Lower bone strength affected both female and male RA +patients and was related to longer disease duration. Impaired bone strength was correlated with altered bone density and microstructural parameters, which were all decreased in RA+. Multivariate models showed that ACPA status (p=0.007) and sex (p<0.001) were independently associated with reduced biomechanical properties of bone in RA. Conclusions In summary, µFEA showed that bone strength is significantly decreased in RA +but not in RA- disease. Reference [1] Macneil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone2008;42(6):1203–13. Disclosure of Interest None declared

OP0131 Innate lymphoid cells correlate with disease activity and bone remodelling in psoriatic arthritis

Background Evaluation of actual immunopathology in psoriatic arthritis (PsA) is challenging. Current composite measures approved for PsA are very useful tools to assess disease activity in clinical routine. Nonetheless, because of subjective patients’ estimations that widely affect the scoring, in particular the distinction between remission and low disease activity is a common question of debate. Innate lymphoid cells (ILC) subsets may couple different aspects of PsA disease activity. Objectives To address whether PsA is associated with an altered composition of innate lymphoid cells and whether such changes are associated with disease activity and structural damage in PsA. Methods 124 patients satisfying the Classification Criteria for Psoriatic Arthritis (CASPAR) and 26 healthy volunteers were enrolled in the study. Information regarding clinical features, laboratory parameters were collected and disease activity score 28 (DAS28), disease activity in psoriatic arthritis (DAPSA), minimal disease activity score (MDA) were calculated. MRI and high-resolution peripheral CT were taken and PsA MRI score (PsAMRIS) was assessed. Flow cytometric analysis was performed and IFNg-producing ILC1s, IL-4/IL-5-producing ILC2s and IL-17/IL-22-producing ILC3s were identified among ILCs. Multivariate linear regression and Receiver-Operating Characteristic (ROC) Curve analysis was performed using the IBM SPSS Statistics software. Results Total number of circulating ILCs were increased in PsA patients compared to healthy controls (p<0,001). Linear regression analyses of the relationship between disease activity and circulating ILC counts showed that ILC2 negatively and ILC1 and ILC3 positively correlated with DAPSA score. The strongest correlation was observed when the ratio of ILC2 to ILC3 was analysed (R=-0.5709; p<0.0001). ILC2/3 ratio was also reduced in patients with active psoriatic skin disease, presence of enthesitis or a history of concomitant uveitis. Extend of synovitis or tenosynovitis or presence of bone erosions or osteophytes on MRI was inversely correlated with the ILC2/3 ratio (R=-0.6753; p<0.0001, R=-0.5828; p=0.0011 and p<0.001 respectively). Consistently, presence of erosions and/or osteoproliferation assessed by HR-pQCT was correlated with a significant lower ILC2/3 ratio. Furthermore, ROC Curve was used to test the performance of the ILC2/3 ratio as marker in differentiating between remission and disease activity of PsA. Indeed, a cut-off 0.57 exhibited highest sensitivity (92.9%) and a 84.7% specificity in identifying remission. Conclusions The ILC2/3 ratio correlates with various facets of PsA manifestations and might be a useful tool to evaluate disease activity in PsA patients. Disclosure of Interest None declared

SAT0628 Increase of cortical micro-channels (COMICS) as a new feature of structural damage in paients with rheumatoid arthritis

Background Bone damage in rheumatoid arthritis (RA) typically emerges at certain anatomical hotspots corresponding to the so-called “bare area”, an intra-articular region between the cartilage and the insertion site of the joint capsule (1,2). We hypothesized that this region exhibits certain micro-anatomical properties, which facilitates the emergence of bone erosions. Objectives To find the micro-structural correlate of the origin of bone erosions in the bare area of the human joint Methods Bare areas of human joints were analyzed for early microstructural changes by in-vivo high-resolution peripheral computed tomography (HR-pQCT). First, bare areas were exactly defined by scanning 6 cadaveric hands for localization of the bare area in the human metacarpal head. Bone lesions found in the cadaveric hand by HR-pQCT were additionally by super-resolution ex vivo micro-CT (μCT40). Then, number and distribution of the type of bare area bone lesion found in cadaveric study were analyzed in a cohort of 105 healthy individuals and 107 anti-citrullinated peptide (ACPA) positive RA patients with similar sex and age distribution. Results HR-pQCT combined with adaptive thresholding allowed the definition of a new type of bone lesions in the bare areas of the human joint termed “COMIC” standing for “cortical micro-channel”. Their existence in the bare area was additionally validated by microCT (Figure 1). RA patients showed significantly (p<0.001) more CoMiCs (112.9±54.7/joint) than healthy individuals (75.2±41.9/joint) with 20–49 years old RA patients exhibiting similar CoMiC numbers as observed in over 65 year old healthy individuals. Importantly, CoMiCs were found in RA patients already very early in their disease course with enrichment in the erosion-prone radial side of the joint. Conclusions CoMiCs represent a new structural feature of the joint, which is characteristic for the bone of the bare area. COMICS at low level are also found in young healthy individuals but they significantly increase with age and particularly with RA. COMICs develop much earlier and much more pronounced in RA patients than in healthy individuals and therefore represent an interesting new early indicator for erosion development in ACPA positive RA patients. References Stach CM, Bauerle M, Englbrecht M, Kronke G, Engelke K, Manger B, et al. Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis & Rheumatism. 2010;62(2):330–9. Simon D, Kleyer A, Stemmler F, Simon C, Berlin A, Hueber AJ,Haschka J, Renner N, Figueiredo C, Neuhuber W, Buder T, Englbrecht M, Rech J, Engelke K, Schett G. Age- and Sex-Dependent Changes of Intra-articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis. J Bone Miner Res. 2016 Oct 27. doi: 10.1002/jbmr.3025. [Epub ahead of print]. Disclosure of Interest None declared

FRI0082 Subclinical MRI Inflammation Does Not Predict Relapse Risk in Rheumatoid Arthritis Patients Tapering Dmards

Background Tapering and stopping DMARD treatment attracts growing interest due to the steady increase in rheumatoid arthritis (RA) patients achieving sustained disease remission. Since only a subset of RA patients in remission can successfully taper or stop these drugs, reliable predictors, which can help to identify patients with high risk for relapse, need to be detected. In the randomized controlled RETRO study1 we recently showed that a serum marker (MBDA) indicating residual inflammation was able to predict the relapse risk in the context of DMARD tapering2. Objectives To test whether presence of residual inflammation in the magnetic resonance imaging (MRI) is associated with a higher relapse risk in RA patients tapering or stopping DMARD treatment. Methods Baseline MRI scans were available from 55 patients of the randomized controlled RETRO study. All patients had RA (ACR/EULAR 2010 criteria) in sustained remission (DAS28 <2,6 for at least 6 months) with stable DMARD treatment for at least 6 months. Patients either continued on their DMARD regimen (Arm1), tapered it by 50% (Arm 2) or stopped it after a 6 month tapering phase (Arm3). Follow-up period was 12 months. MRI scans were scored for synovitis, osteitis and tenosynovitis according to RAMRIS and Haavardsholm scores3,4. Results MRI synovitis was found in 58%, MRI osteitis in 26% and MRI tenosynovitis in 24% of the patients. Prevalence of baseline MRI changes did not differ between patients experiencing relapse of RA or remaining in remission (62% in both groups, p=0,981). Also, baseline MRI scores were not different between patients relapsing or not relapsing: Median (IQR) total RAMRIS scores in the relapse group were 9 (3,5–48) and in the non-relapse group 8 (2,75–14,5) (p=0,27), median synovitis scores were 3 (0–7) and 1 (0–6) (p=0,65), median osteitis scores 0 (0–0,25) and 0 (0–3,5) (p=0,48) and tenosynovitis scores 0 (0–0,25) and 0 (0–0,5) (p=0,82) respectively. Furthermore, MRI synovitis, osteitis and tenosynovitis scores were not different between ACPA+ than ACPA- individuals (p=0,80, 0,82, and 0,95, respectively). Conclusions Subclinical MRI changes are frequent in RA patients in sustained remission but do not predict the risk of disease relapse during DMARD tapering. References Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy:interim results from the prospective randomized controlled RETRO study. Haschka J.et al. Ann Rheum Dis, 2015. Published online first 6 Feb 2015. doi:10.1136/annrheumdis-2014-206439 Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment. Rech J,et al. Ann Rheum Dis, 2015. Published online first 19 October 2015 doi:10.1136/annrheumdis-2015-207900 OMERACT rheumatoid arthritis magnetic resonance imaging studies.Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. Ostergaard M, et al. J Rheumatol 2003;30;1385–1386 Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis:reliability in a multireader longitudinal study. Haavardsholm EA, et al. Ann Rheum Dis 2007;66:1216–1220 Disclosure of Interest None declared