A. Nzeusseu Toukap

Oral pamidronate prevents high-dose glucocorticoid-induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients.

Glucocorticoid (GC)-induced osteoporosis contributes to chronic damage in patients suffering from connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE). In this study, performed in an highly selected cohort of premenopausal female CTD (mostly lupus) patients, given high-dose GC therapy for severe disease, we show that lumbar spine bone loss can be averted by treatment with oral disodium pamidronate combined with calcium salts and vitamin D3 supplements and not by calcium salts and vitamin D3 supplements alone. We stress the need for optimal GC-induced bone loss prevention therapy in premenopausal patients, a too often neglected issue in patients whose survival has dramatically improved over the last decades.

The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

Myeloperoxidase and its products in synovial fluid of patients with treated or untreated rheumatoid arthritis.

Abstract Objective. Plasma and synovial myeloperoxidase (MPO) and its products were strongly associated with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, it is well known that there is a link between oxidative stress and cytokines. The present study aims at investigating the link between synovial MPO (and its products), interleukin (IL)-18, which is involved in the degradation of articular cartilage in RA, and IL-8, which is involved in recruitment and activation of neutrophils during inflammation. Effects of the treatment of RA on the biological parameters were also investigated. Methods. Patients (n = 105) were studied including 39 patients with OA, 33 with RA and 33 with RA receiving a specific treatment. Disease activity score (DAS-28) was calculated whereas MPO antigen/activity, neutrophils, chloro-tyrosine (Cl-Tyr), homocitrulline (Hcit), IL-8, and IL-18 were measured in synovial fluid (SF) and CRP was measured in serum. Results. DAS-28 and CRP levels were not significantly different between groups. MPO activity, and MPO, Cl-Tyr, and Hcit levels were significantly higher in SF of RA patients than OA patients. MPO specific activity (MPO activity/antigen ratio) was significantly lower in treated than in untreated RA patients as was IL-8. MPO activity and concentration were correlated with IL-8 and IL-18 in untreated but not in treated RA patients. Conclusions. MPO level is related to IL-8 and IL-18 levels in untreated RA patients. A link has been shown between treatment and decrease of IL-8, MPO specific activity and Hcit in SF. The causal role of MPO in SF inflammation and how treatment can affect MPO specific activity need further investigations.

FRI0633 Which are the ultrasound lesions underlying dactylitis

Background Dactylitis, defined as a diffuse swelling of a digit is a hallmark feature of peripheral spondyloarthritis (SpA), particularly in psoriatic arthritis, with a prevalence between 16% and 481. Objectives This study aims to assess the frequency of the pathological lesions in dactylitis using ultrasonography (US) and to evaluate their association with patient-reported tenderness. Methods Thirty-four dactylitis from 20 consecutive patients suffering from peripheral spondyloarthritis were examined by ultrasound. At US examination, the entire digit was scanned both on dorsal and palmar/plantar sides. The following US pathological lesions were scored: soft tissue thickness, soft tissue edema, soft tissue vascularization, synovitis of metacarpophalangeal (MCP)/metatarsophalangeal (MTP), of proximal interphalangeal (PIP) and of distal interphalangeal (DIP) joints, inflammatory involvement of both flexor (tenosynovitis) and extensor (paratenonitis) tendons, nail bed vascularization, synovio-entheseal complex at DIP level, enthesitis of flexor tendon, and bone proliferation. Grey-scale (GS) and power-Doppler (PD) synovitis and tenosynovitis were assessed according to OMERACT scores (0–3). Nail bed vascularization was scored 0 to 3. The other US lesions were scored 0 (absent) or 1 (present), both in GS and PD. The standard (HAQ) questionnaire, tender and swollen joint count, patient-reported tenderness, global disease activity scored by physician and by patient were assessed in all patients. Results Twelve (60%) patients presented hand and 8 (40%) patients foot dactylitis. Twelve (60%) patients had single dactylitis. Eight patients presented with multiple dactylitis: 4 dactylitis in 1 patient, (5%), 3 dactylitis in 4 patients (20%) patients and 2 dactylitis in 3 (15%) patients. Soft tissue thickening was present in all 34 dactylitis. MCP/MTP joint synovitis was present in 28 digits (82%), PIP joint synovitis in 23 digits (68%) and DIP joint synovitis in 17 digits (50%). Extensor paratenonitis was observed in 21 digits (62%) and flexor tenosynovitis in 20 digits (59%). Enthesitis of extensor tendons was present in 21 digits (62%) and enthesitis of flexor tendon in 5 digits (15%). Osteoproliferation was present in 21 digits (62%). The frequency of synovitis, tenosynovitis and enthesitis did not differ significantly between tender (n=25) and non-tender (n=9) dactylitis. A significant association between tenderness and the presence of power Doppler (χ2:17.9, p<0.01) and of edema in the soft tissue was observed (χ2:11.5, p<0.01). Conclusions Dactylitis is a multi-compartment digit disease, and anatomical lesions are more heterogenous than previously described. A significant amount of joint, tendon and entheseal inflammation persists in non-tender dactylitis. Patient-reported tenderness is associated with the presence of edema and/or power Doppler inside the soft tissue. References Bakewell CJ et al. OMERACT Ultrasound Task Force. Ultrasound and magnetic resonance imaging in the evaluation of psoriatic dactylitis: status and perspectives. J Rheumatol. 2013;40:1951–7. Acknowledgements We acknowledge S. Aydin and the OMERACT/EULAR working group for fruitful discussions. Disclosure of Interest None declared

AB0814 The BEPAS Cohort: A Prospective Cohort of Psoriatic Arthritis in Belgium: Study Design and Baseline Characteristics of the 461 Recruited Patients

Background Psoriatic arthritis is a chronic arthritis with major impact on the physical and psychosocial integrity of the patient. Only few prospective data are available. BEPAS (Belgian Epidemiological Psoriatic Arthritis Study) is a large prospective multicenter cohort set up in 17 Belgian rheumatology practices. Objectives (1) to generate a comprehensive database in order to characterize the clinical presentation and the frequency of the distinct PsA subtypes; (2) to estimate the severity of disease based on disease activity scores, active inflammation and structural damage; (3) to estimate the impact in terms of health-related quality of life of PsA in Belgium and (4) to evaluate progression of structural damage in patients with PsA over time. Methods Patients with an existing or a new clinical diagnosis of PsA and fulfilling the CASPAR classification criteria were recruited.A specific selection rule was applied to avoid selection bias. All patients gave informed consent. Recruitment of the patients occurred in 17 large rheumatology centers across Belgium. In the prospective study, patients are followed every year during the first 2 years with a possible extension for an additional 5 years. Demographics and clinical parameters, and additional information about QoL and disability were collected. X-rays of hands and feet are performed every year and axial X-rays every 2 years. Results 461 patients (mean age: 52.79 years (±12.29), male 57%) were recruited in the 17 centers from december 2012 to July 2014. Average time between first complaints and diagnosis of PsA was 8.6 yrs (±9.3), 27.5% of the patients had a disease duration of less than 2 years. Combined peripheral and axial involvement was reported in 73.7% of the patients, only peripheral involvement in 25,4% and only axial involvement in 0.7% of the patients. At entry polyarticular, oligoarticular and monoarticular joint involvement was reported in respectively 25.8%, 12.2% and 8.9% of the patients. Dactylitis and enthesitis were reported in respectively 11.3% and 14% at entry. Psoriasis type1 (onset <40 year) was present in 64.6%. Plaque psoriasis is the most frequent presentation (92.8%). Nail involvement was present at baseline in 39.8% of the patients. At entry the mean number of swollen joints is 2.13 (±4.53) and of tender joints is 4,10 (±7.31). Conclusions This large cohort paints a real-life heterogeneous presentation of PsA in Belgium. Further data collection and analysis should facilitate clinical and outcome studies in order to improve our knowledge on the impact and natural history of PsA in Belgium. Acknowledgements This study was sponsored by MSD Disclosure of Interest K. de Vlam Grant/research support from: MSD, R. Lories: None declared, S. Steinfeld: None declared, F. Van Den Bosch: None declared, A. Nzeusseu Toukap: None declared, M. Malaise: None declared, V. Taelman: None declared, F. Van Bruwaene: None declared, M. Vanden Berghe: None declared, R. Joos: None declared, J. Lenaerts: None declared, P. Geussens: None declared, S. DalliArmellina: None declared, I. Peene: None declared, G. De Brabanter: None declared, M. Van Den Berghe: None declared, J. Qu: None declared, M. Maertens: None declared, H. Leroi Employee of: MSD

OP0129 Higher Expression of TNF Alpha-Induced Genes in the Synovium of Early RA Patients Correlates with Disease Activity, and Predicts Absence of Response to First Line Therapy

Background Gene expression profiling studies indicate that IL6-related T cell activation, and TNFα-dependent cell proliferation are major targets of therapy in the RA synovium1. We investigated whether expression of these pathways in early RA synovial biopsies is associated with clinically relevant information. Methods We performed global transcriptomic studies (HGU133 Plus2.0) on early RA synovial biopsies, (GSE45867) and in TNFα-stimulated synovial fibroblasts (GSE15615). Immunostaining experiments (GADD45B, PDE4D) were performed on independent sets of early untreated RA samples, obtained by needle-arthroscopy (n=46), or by US-guided biopsies (n=35), next quantitated digitally. Results In an initial set of 20 untreated early RA patients, 1,431 transcripts displayed at least a moderate correlation (r >0.4) and 77 of them displayed a good correlation (r >0.6) with DAS28-CRP. T cell associated genes were enriched in the 0.4 – 0.6 correlation range, while 38 out of the 77 transcripts with a correlation >0.6, were found to be induced by TNFα in cultured synovial fibroblasts (GADD45B, PDE4D, and CXCL14 were represented several times, by different probe sets). Immunostaining experiments on 46 independent synovial biopsy samples confirmed a higher PDE4D (median score 3.23 vs. 0.57, p =0.04) and GADD45B (median 0.60 vs. 0.31, p =0.09) staining in patients with DAS28-CRP >5.1. Higher synovial expression of TNFα-induced genes predicts absence of response to TNF blockade in MTX-resistant RA patients2. We therefore wondered whether higher expression of these genes at baseline also predicts absence of response to first line therapy in early RA. In the microarray data, expression of 6 (GADD45B (x2), PDE4D, ADAMTS1, WWP2, MPPED1) out of 38 TNFα-dependent probe sets was significantly higher in patients who did not reach SDAI remission at month 6 in response to MTX therapy (all patients were DAS responders). In an independent group of patients, immunostaining of GADD45B (median score 2.39 vs. 0.29, p =0.002) and PDE4D (median score 5.47 vs. 0.48, p =0.002) produced a higher signal in baseline synovial biopsies of 14 EULAR non-responders (at 3 months) out of 46 early RA patients who received first line therapy, and in 8 non-responders out of the 16 who received methotrexate as a first line agent (GADD45B: 2.87 vs. 0.25, p =0.01; PDE4D: 7.74 vs. 0.48, p =0.07). Similarly, GADD45B immunostaining in US-guided biopsies was significantly higher at baseline in another set of 15 non-responders out of 35 early RA patients treated with MTX (median 0.76 vs. 0.22, p =0.03); no significant difference in PDE4D staining was observed in this set of samples. Disease activity at baseline itself did not predict response to therapy. Conclusions Higher expression of TNFα-induced transcripts in early RA synovitis drives disease activity, and predicts poor response to first-line therapy. These results are important for patients stratification in clinical trials, and open perspectives in terms of personalized medicine approaches in clinical practice. References Ducreux J, et al. Arthritis Rheum 66: 15-23. Badot V, et al. Arthritis Res Ther 11: R57 Disclosure of Interest A. De Groof: None declared, F. Humby: None declared, J. Ducreux: None declared, S. Kelly: None declared, A. Nzeusseu Toukap: None declared, C. Pitzalis: None declared, P. Durez: None declared, B. Lauwerys Shareholder of: DNAlytics

THU0108 Global molecular effects of tocilizumab therapy in synovial biopsies of early RA patients

Background Tocilizumab is an approved humanized anti-IL-6 Receptor antibody with proven therapeutic benefits in the treatment of patients with RA. Objectives This study aimed to investigate the global molecular effects of Tocilizumab versus Methotrexate therapy in synovial biopsy samples obtained from early RA patients harvested prospectively before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients. Methods Paired synovial biopsy samples were obtained from the affected knee of early RA patients before and 12 weeks after initiation of Tocilizumab (n=12) or Methotrexate (n=8) therapy. Total RNA was extracted, labeled according to standard Affymetrix procedures, and hybridized on GeneChip HGU133 Plus 2.0 slides. Quantitative real-time reverse transcriptase-polymerase chain reaction (qPCR) experiments were performed to confirm the differential expression of selected transcripts. Results We found that Tocilizumab induces a significant down-regulation of genes included in specific pathways: cytokines (IL-6, IL-7, IL-22, ...) & chemokines (CCL8, CCL11, CCL13, CCL19, CCL20, CXCL5, CXCL13, ...), and T cell activation. By contrast, Tocilizumab induces a significant up-regulation of genes associated with healing processes. These effects are significantly more pronounced as compared with the effects of Methotrexate, Rituximab, and Adalimumab therapies. Real-time qPCR experiments, performed until now, confirm the down-regulation of CXCL13 and up-regulation of BMPR1A expression following Tocilizumab treatment. Conclusions Tocilizumab displays distinct molecular effects on synovial biopsies of RA patients. These results open perspectives for the individualization of therapeutic decisions, based on the molecular profiles of the patients. Disclosure of Interest None Declared