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Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Peter C Taylor,1 Codrina Ancuta,2 Orsolya Nagy,3 María C de la Vega,4 Andrey Gordeev,5 Radka Janková,6 Umut Kalyoncu,7 Ivan Lagunes-Galindo,3 Jadranka Morović-Vergles,8 Mariana Peixoto GU e Silva de Souza,9 Bernadette Rojkovich,10 Prodromos Sidiropoulos,11 Atsushi Kawakami12 1Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; 2Department of Rheumatology, “Grigore T. Popa” University of Medicine and Pharmacy, Iași, Romania; 3AbbVie Inc, North Chicago, IL, USA; 4CEIM Investigaciones Medicas, Buenos Aires, Argentina; 5V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation; 6Department of Pediatric and Adult Rheumatology, Faculty Hospital Motol, Prague, Czech Republic; 7Department of Internal Medicine, Division of Rheumatology, Hacettepe University, Ankara, Turkey; 8Department of Internal Medicine, Division of Clinical Immunology, Allergology and Rheumatology, Dubrava University Hospital, University of Zagreb School of Medicine, Zagreb, Croatia; 9Santa Casa de Belo Horizonte, Belo Horizonte, Brazil; 10Department of Rheumatology and Physiotherapy, Polyclinic of the Hospitaller Brothers of St. John of God, Semmelweis University, Budapest, Hungary; 11Faculty of Medicine, University of Crete, Heraklion, Greece; 12Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanCorrespondence: Peter C TaylorBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Headington, Oxford, OX3 7LD, UKTel +44 1865 227323Email peter.taylor@kennedy.ox.ac.ukBackground: Patients’ needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients’ perspectives can help identify unmet needs and enhance the understanding of treatment benefits.Objective: The SENSE study assessed the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management.Methods: SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed.Results: A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥ 80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were “general improvement of arthritis” and “less joint pain”. Most patients preferred oral RA medications (60.7%) and rapid (≤ 1 week) onset of action (71.1%). “Increased risk for malignancies” and “increased risk for cardiovascular disease” were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients.Conclusion: Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decision-making and optimize treat-to-target strategies for improving patient outcomes in RA.Keywords: adherence, digital health literacy, patient preference, rheumatoid arthritis, treatment satisfaction

Availability of biosimilar medicines is rapidly increasing, potentially leading to a wider prescription and a support for healthcare system costs. Despite efforts of patient and physician educational initiatives there still remains a reluctance in prescribing or administering this type of products. A multi-centric survey was conducted on 336 patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA) or lupus (SLE) on biologic treatment. Half of the patients stated never hearing of biosimilars and one third feared adverse events (infections, cancer). Another 20% felt insecure on drug tolerability or efficacy. However, the majority declared relying on their rheumatologist if prescribing a biosimilar. Lack of patient information should be accurately addressed by health organizations so that the choice of treatment is done knowingly.

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

Objective. Cardiovascular disease (CVD) is considered to be the main cause of morbidity and mortality in rheumatoid arthritis (RA) patients. Tumor necrosis factor alpha (TNF), an important pro-inflammatory cytokine, has a multivalent role in the pathogenesis of RA. It is also responsible for the glucose metabolism related alterations and for the increased levels of serum lipids found in these patients. We aimed to evaluate the effects of TNF inhibitors on lipid and glucose metabolism in patients with active RA. Methods. We performed a prospective study in 117 consecutive patients with active RA undergoing periodic treatment with TNF inhibitors – Adalimumab (ADA), Etanercept (ETA), Infliximab (IFX) –, combined with conventional synthetic disease modifying antirheumatic drugs (csDMARDs), according to the national recommendations for the treatment of RA. At the time of the enrollment, all patients were assessed according to a predefined protocol including demographics and RA-related parameters (inflammatory syndrome, disease activity, medication) as well as metabolic biomarkers such as total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TG) and serum glucose level. Statistical analysis was performed in STATA 12/SE software, p

Pregnancy in autoimmune rheumatic diseases remains a real challenge in clinical practice due to complex interplay between disease activity, pregnancy and drugs, and account for potential influence of pregnancy on rheumatic condition and the impact of disease on pregnancy outcomes. Indeed, innovative and successful therapies have dramatically improved the quality of life in immune-mediated rheumatic conditions and, subsequently, allowed more patients of reproductive age to plan a pregnancy/to conceive. The purpose of this chapter is to discuss emerging data about the interaction of pregnancy and systemic erythematosus lupus (SLE) focusing on modulation of the immune system by pregnancy, pregnancy outcomes in women with active lupus, biomarkers of adverse pregnancy outcomes (APO) including predictors of pre-eclampsia, predictors of obstetric complications in SLE, the influence of autoantibodies on fetal health, and, finally, evidence about rheumatologic and obstetric follow-up. There are still unmet needs in this new field of reproductive rheumatology and it becomes crucial that researchers, physicians (rheumatologists, specialists in maternofetal medicine, obstetricians) and midwifes share their knowledge and expertise in counseling women with SLE wishing to conceive, assisting pregnancy and managing different issues related to APO as well as drug optimization in preconception, during pregnancy and postpartum period.

Objectives The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

BackgroundPatients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression.MethodsThis was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient’s lifetime.ResultsThe analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p p p ConclusionsHAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Musculoskeletal pathology reaches important proportions in dental practitioners. Besides the articular manifestations of inflammatory or degenerative rheumatism, in daily practice we often find patients suffering from abarticular pathological processes, during which tendons, synovial dysplasia, schizophrenia, fascia, aponevrozes are affected. The Carpal Tunnel Syndrome represents a compressive neuropathy of the median nerve inside the carpal tunnel of the wrist. Any condition that lowers the dimensions of the carpal tunnel can cause symptoms of carpal tunnel syndrome. The carpal channel (Carpal Tunnel) is divided by a sagittal fibrous divider into two osteofibrosis osteofibrosis: medial and lateral. This blade separates from the posterior aspect of the flexor retina and is inserted into the carpal bones (scaffold, trapezoid and capita). This syndrome has received particular attention in recent years due to the fact that it can occur in people whose work involves repetitive hand activities. Repeated use of the hand, repetition of the same movements and activities of the hand and wrist, over a long period of time, can cause inflammation of the tendons in the wrist, causing swelling, which puts pressure on the nerve. Symptoms of Carpal Tunnel Syndrome begin gradually - without specific trauma. It is a gradual process for most people, carpal tunnel syndrome is aggravated over time without appropriate treatment. The study includes a batch of 75 dentists from Galati County, selected following the application of the inclusion criteria referring to the presence of signs and symptoms characterizing carpal tunnel syndrome in 2015-2017. Sensitivity disorders and paraesthesias accompanying nerve suffering are symptoms that create discomfort and contributes to the deterioration of pretension and force so useful to the professional act of dental medicine. Perceived cramping pain, often of moderate intensity, located at the fist and distal in the distribution area of the median nerve, rarely the pains are intense and radiate upward along upper limb to shoulder.

Background:Despite the availability of advanced therapies, many patients with rheumatoid arthritis (RA) do not achieve their treatment goals. Understanding geographic influence on patient perspectives and physicians’ attitudes toward treatment adjustments may inform region-specific strategies to improve outcomes in RA.Objectives:To explore differences in treatment satisfaction, patient preferences, and treatment strategies between patients from Europe (EU), South America (SA), and Japan (JP) with suboptimal control of RA.Methods:This is a subgroup analysis of SENSE, a non-interventional cross-sectional study in adults with RA who had moderate/high disease activity as measured by Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28[ESR]) >3.2, despite disease-modifying antirheumatic drug (DMARD) treatment. Patient satisfaction and preferences, treatment adherence, patient-reported outcomes, and physicians’ plans for DMARD switch were assessed as previously described.1 Predictors of good treatment satisfaction and physician’s decision not to switch DMARDs were identified using multiple logistic regression analyses.Results:Of 1234, 272, and 118 patients enrolled from EU, SA, and JP, respectively, 13.9%, 15.4%, and 5.9% reported good treatment satisfaction. Irrespective of region, patients reported impaired quality of life and good treatment adherence, and around one-third of patients received targeted synthetic (ts) or biologic (b) DMARDs. Among patients treated with ts/bDMARDs, monotherapy was most common in SA (45.3%), followed by EU (26.3%) and JP (18.8%), consistent with a greater acceptance of combination therapy in JP. More than 80% of JP patients preferred oral treatments versus Table 1.Predictors for good treatment satisfaction and no treatment switch plannedOR (95% CI)Europe(n=1234)South America(n=272)Japan(n=118)Good treatment satisfaction (TSQM global treatment satisfaction ≥80)Current treatment with ts/bDMARDs3.8 (2.7, 5.4)****4.9 (2.2, 10.8)****—Psychiatric disorders2.4 (1.3, 4.6)**3.1 (1.2, 8.4)*—Number of comorbidities——2.3 (1.2, 4.3)*Worst joint pain—1.3 (1.1, 1.5)**SF-36 MCS1.0 (1.0, 1.1)****—1.3 (1.1, 1.5)**SF-36 PCS1.1 (1.0, 1.1)****——Work Productivity and Activity Impairment–Rheumatoid Arthritis:Total activity impairment—1.0 (1.0, 1.0)***—DAS28(ESR) >5.1—0.3 (0.1, 0.7)**—Female——0.1 (0.0, 0.9)*No treatment switch plannedCurrent treatment with ts/bDMARDs3.9 (3.0, 5.2)****2.4 (1.4, 4.2)**—Number of comorbidities1.2 (1.1, 1.4)****——Age——1.0 (1.0, 1.1)*TSQM effectiveness subscore1.0 (1.0, 1.0)***1.0 (1.0, 1.0)***—Number of concomitant medications0.9 (0.8, 1.0)**——DAS28(ESR)0.5 (0.5, 0.6)****0.6 (0.5, 0.8)***0.6 (0.4, 0.9)*X2 test: ****pCI, confidence interval; OR, odds ratio; SF-36 M/PCS, 36-Item Short-Form Survey mental/physical component summary; TSQM, Treatment Satisfaction Questionnaire for MedicationConclusion:In patients with moderate to high RA disease activity, current disease control was a common determinant of treatment switches. Predictors for good treatment satisfaction revealed region-specific patient attitudes to treatment acceptance despite poor disease control.References:[1]Taylor PC, et al. Ann Rheum Dis 2020;79:996–7Acknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of this abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Hilary Wong, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Peter C. Taylor Speakers bureau: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly, Fresenius, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB., Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly, Fresenius, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB., Grant/research support from: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly, Fresenius, Galapagos, Gilead, GSK, Janssen, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB., Prodromos Sidiropoulos Speakers bureau: AbbVie, Amgen, MSD, Novartis, Pfizer, Roche, and UCB., Consultant of: AbbVie, Amgen, MSD, Novartis, Pfizer, Roche, and UCB., Grant/research support from: AbbVie, Amgen, MSD, Novartis, Pfizer, Roche, and UCB., CODRINA ANCUTA Speakers bureau: AbbVie, Eli Lilly, Ewopharma, MSD, Novartis, Pfizer, Roche, and UCB., Consultant of: AbbVie, Eli Lilly, Ewopharma, MSD, Novartis, Pfizer, Roche, and UCB., Ivan Lagunes-Galindo Employee of: AbbVie employee and may own stocks or options, Maria DeLaVega: None declared, Umut Kalyoncu Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB., Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB., Orsolya Nagy Employee of: AbbVie employee and may own stocks or options, Atsushi Kawakami Speakers bureau: AbbVie, Actelion, Asahi Kasei, Astellas, Boehringer Ingelheim, Celltrion, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, GSK, Janssen, Kowa, MedPeer, Mitsubishi Tanabe, Novartis, ONO, Pfizer, Taisho, and Takeda, Grant/research support from: AbbVie, Actelion, Asahi Kasei, Astellas, AYUMI, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Hakko Kirin, MSD, Neopharma, Novartis, ONO, Sanofi, Taisho, Takeda Science Foundation, and Teijin.

The main aim of our study was to perform a biochemical analysis of the saliva and to assess potential impact on oral health, particularly cariogenic issues, in patients with salivary secretory dysfunction such as primary Sjogren�s syndrome (pSSj). Consecutive pSSj and healthy age-matched controls were prospectively assessed for (i) whole saliva flow rates (unstimulated, RFR, and stimulated, RFS), pH and composition; (ii) cariogenic scores - decayed, missing and filled tooth surfaces (DMFS index), Silnes and Loe bacterial plaque index (PI). Salivary flow rates were significantly lower in pSSj for both unstimulated and stimulated tests (p[0.05), with a drop in pH as compared to healthy controls (p[005). Abnormal inorganic and organic saliva composition was reported in all cases comprising higher sodium, lower potassium and chloride concentrations, higher amylase activity and lower total protein (p[0.05). Statistically significant higher cariogenic scores particularly DMFS, were demonstrated in all pSSj (p[0.05). In conclusion, patients with pSSj are at increased risk to develop cariogenic issues due to both quantitative and qualitative salivary changes.

Although the relation between periodontitis (PD) and systemic disorders (e.g. cardiovascular diseases, diabetes and rheumatoid arthritis) is widely accepted, the association with ankylosing spondylitis (AS) is inconsistently mentioned. We prospectively examined the relationship between periodontal disease and AS, focusing on the rate and course of PD, factors associated with severity and the impact of anti-TNF-a treatment on inflammatory status. Standard assessments performed twice (week 0, week 24) included an extensive dental evaluation (plaque index, gingival index, bleeding on probing, periodontal pocket depth, clinical attachment loss), inflammatory parameters and AS activity scores (BASDAI, ASDAS-CRP). More than half of AS presented with impaired periodontal health at baseline (mild to moderate PD) meaning increased sites with dental plaque, abnormal bleeding, increased periodontal pocket depth and clinical attachment loss. Significant positive correlation between presence and severity of PD, AS activity and systemic inflammation (CRP) was reported at baseline (p[0.05). A final analysis performed at 24 weeks revealed significant improvement in periodontal status, inflammatory parameters and AS activity, suggesting efficacy of TNF inhibitors directed not only against systemic, but also on local (articular, periodontal) inflammation (p[0.05). Patients with AS are at risk to develop periodontal disease, particularly those with high levels of systemic inflammation. Benefits of anti-TNFa therapy in the particular settings of AS patient and concomitant periodontal disease should be validated through further studies in larger cohorts.

Classified as a distinct subset of idiopathic inflammatory myopathies, anti-synthetase syndrome is an orphan autoimmune disease characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies associated with a spectrum of clinical features including interstitial lung disease, myositis or dermatomyositis, chronic polyarthritis, fever, mechanic‘s hands and Raynaud‘s phenomenon. The main objective of our study was to evaluate nailfold capillary abnormalities in a series of cases diagnosed with anti-synthetase syndrome, aiming to describe capillaroscopy findings and to identify potential relation with clinical and functional outcomes. Irrespective of clinical and serological disease subtype, significant capillaroscopic changes may help diagnosis and identify negative prognostic factors, advancing the role of routine capillaroscopy in the decisional algorithm of anti-synthetase syndrome. Nailfold videocapillaroscopy is able to provide valuable information in patients with anti-tRNA synthetase myositis, suggesting that diffuse microangiopathy represents an early pathobiologic event.

Dental pathology is commonly described among patients with systemic sclerosis (SSc), a multisystem autoimmune disorder, and assumed to be multifactorial. We aimed to evaluate the periodontal status and to identify potential relation with SSc-specific parameters as well as serum lipid profile in a cross-sectional study on consecutive SSc. Standard assessments comprised dual, rheumatologic (disease subtype, clinical spectrum, inflammatory, immunological, lipid metabolism - total cholesterol and fractions, triglycerides), and dental evaluation (plaque index, bleeding on probing, pocket depth, clinical attachment level). 70.96% SSc developed oral manifestations, 51.61% periodontal disease, while one third severe aggressive periodontitis, particularly in diffuse SSc (p[0.05). Abnormal lipid pattern (low serum HDL- and high LDL-cholesterol, increased serum triglycerides, without significant modification in total cholesterol level) significantly correlated with diffuse SSc and skin involvement, disease duration, anti-topoisomerase 1 positivity, SSc activity and severity, as well as periodontitis (p[0.05). Our results clearly define an association between the presence and severity of periodontal disease and lipid anomalies in SSc, suggesting a potential link with early atherosclerosis via gingival inflammation and altered lipid metabolism.

We report the clinical case of an emergent Crohn’s disease (CD) as a paradoxical effect after 24 months of successfully treatment with etanercept for active ankylosing spondylitis in a young women. Despite rapid and sustained response of articular disease (remission achieved as soon as three months and maintained through the entire period of administration), new onset intestinal manifestations developed during biological therapy. A complex assessment comprising clinical, endoscopic and histopathologic evaluation, associated with high levels of fecal calprotectin confirmed drug-induced inflammatory bowel disease (IBD) compatible with CD. Although optimal treatment strategy is not yet validated, discontinuation of putative etanercept and cycling to a monoclonal anti-TNF antibody (adalimumab) demonstrated positive outcomes for both articular and IBD. New onset CD may be considered as an immune-mediated injury induced etanercept and should be considered in any patient with spondylarthritis in whom IBD develops with a clear temporal relationship with TNF inhibitors, especially etanercept.

Although the relationship between periodontal disease and rheumatoid arthritis (RA) is widely documented, centered by common pathobiologic pathways, the effect of various tumor necrosis factor alpha (TNF) antagonists in modulating not only inflammatory and immune articular damage, but also periodontal microenvironment remain debatable. We aimed to evaluate the periodontal status with and without TNF inhibitors in RA patients and to identify potential relation among these entities. We performed a prospective longitudinal 6-months analysis on 96 RA initiating their first biological therapy. Standard assessments included a dual rheumatologic (RA activity, disability, serological, inflammatory prolife) and dental evaluation such as plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), clinical attachment level (CAL). More than half of RA presented at baseline with chronic periodontitis, as suggested by high prevalence of sites with dental plaque, abnormal BOP, PD and CAL. Advanced inflammatory (CRP, ESR) and immune (anti-cyclic citrullinated peptide antibodies, ACPA) markers were described in RA subsets presenting with aggressive periodontal diseases, while significant correlations between dental pathology, RA activity and ACPA levels were also reported (p[0.05). Furthermore, we revealed significant improvement in both RA-related characteristics and periodontal status after 6 months of anti-TNF therapy (p[0.05). RA, particularly active severe, ACPA positive disease, is essentially accompanied by comorbid periodontal disease. TNF blockade is efficient in patients with active RA and potentially able to modulate the inflammatory process in the periodontal tissue.

Background:Patient characteristics, their treatment preferences and goals are important determinants of treatment success in rheumatoid arthritis (RA).Objectives:SENSE study aimed at assessing the impact of inadequate response to disease-modifying anti-rheumatic drugs on disease outcomes, and analyze their attitude, their treatment and disease.Methods:Non-interventional, cross-sectional study conducted in 18 countries in Europe, Asia, and America. Adult RA patients with moderate/high disease activity were eligible. Patient satisfaction was assessed by Treatment Satisfaction Questionnaire for Medication, Version 1.4 (TSQM v1.4). Treatment adherence, patient preferences, and expectations were evaluated by visual analog scale. eHealth Literacy Scale was employed for evaluating DHL. Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis, v2.0 (WPAI-RA) was used to assess workability and patient documentation for healthcare resource utilization (HRU).Results:1624 patients were included in this analysis; most were female (84.2%), middle-aged, and had a mean (standard deviation [SD]) disease duration of 10.5 (9.3) years. 11.9% of the patients had retired early and 6.0% were unemployed due to RA. Mean (SD) total WPAI-RA score was 55.1% (26.7). In the previous 3 months, the mean (SD) number of healthcare professional and emergency room visits were 2.2 (2.5) and 1.6 (1.3), respectively. Mean (SD) TSQM v1.4 global satisfaction subscore was 60.9 (20.9), with only 13.5% reporting good treatment satisfaction (TSQM global ≥80). The leading treatment expectations were ‘general improvement of arthritis’, ‘less joint pain’, and ‘lasting relief of RA symptoms,’ with mean (SD) scores of 5.7 (1.6–1.7) for each. 60.7% of patients preferred oral administration and 31.3% preferred not to use drug combinations for RA. Preferred time to effect was predominantly ‘up to one week’ (71.1%). Least frequently side effects rated ‘acceptable’ were ‘increased risk for malignancies’ (3.5%) and ‘increased risk for cardiovascular diseases’ (3.3%). Most patients (67.4%) had poor DHL. Good adherence (in 87.4% of patients) was significantly associated with lower levels of joint pain.Conclusion:Suboptimal disease control has a significant impact on satisfaction, workability, and HRU. Our results can support shared decision-making when setting RA treatment strategy.Disclosure of Interests: :Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Orsolya Nagy Shareholder of: AbbVie, Employee of: AbbVie, Maria DeLaVega: None declared, Andrey Gordeev Speakers bureau: AbbVie, Eli Lilly, Pfizer, Sanofi, Bristol-Myers Squibb, Merck Sharpe and Dohme, Roche, and UCB., Radka Jankova Speakers bureau: AbbVie, Eli Lilly, Pfizer, Sanofi, Bristol-Myers Squibb, Merck Sharpe and Dohme, Roche, and UCB, Umut Kalyoncu Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB., Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB., Ivan Lagunes-Galindo Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jadranka Morovic-Vergles Speakers bureau: Abbvie., Roche, MSD, Eli Lilly, Pfizer, Mylan, Amgen, Fresenius Kabi, Mariana Peixoto GU e Silva de Souza Grant/research support from: AbbVie, UCB, Bristol-Myers Squibb, Pfizer, and GSK, Consultant of: AbbVie, Roche, UCB, Pfizer, and Jansen, Speakers bureau: AbbVie, Roche, UCB, Pfizer, and Jansen, Bernadette Rojkovich: None declared, Prodromos Sidiropoulos: None declared, Atsushi Kawakami: None declared

Background:Despite emerging vaccines, the world is in the midst of a coronavirus disease 2019 (COVID-19) pandemic. Outcomes of SARS-CoV2 infection remain a major concern in patients with rheumatic and musculoskeletal diseases, especially for those with uncontrolled disease.Objectives:We aimed to investigate trends and outcomes of COVID-19 occurring in patients with chronic inflammatory rheumatic conditions treated with biologics and targeted synthetic disease modifying antirheumatic drugs (bDMARDs, tsDMARDs).Methods:We included all confirmed cases of COVID-19 regardless of severity in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) undergoing bDMARDs or tsDMARDs treatment registered in our local COVID-19 reporting database. We collected relevant information about comorbidities, rheumatologic-related clinical activity (RAPID5, SDAI, BASDAI, DAPSA), type of DMARD and glucocorticoid use, as well as COVID-19 related data as severity (ranging from asymptomatic to life-threatening forms), medication, hospitalization, intensive care unit admission, invasive mechanical ventilation and death.We did a subgroup analysis among patients with a specific rheumatologic diagnosis, among different class of medication, patients who were or not hospitalized with COVID-19 looking how age, comorbidities, type of rheumatic condition and treatments impact COVID outcomes.Results:40 COVID-19 cases (positive PCR for SARS-CoV2) (4.67%) were identified during the 6-month study period among 855 patients registered in our database of patients under biologic treatment, including 20 RA, 18 SpA, 2 PsA patients. The majority were in either low disease activity or remission, only two patients had active uncontrolled disease at the onset of coronavirus infection.16 cases (40%) were asymptomatic and were tested RT-PCR-positive during routine follow-ups for their disease, 13 cases (32.5%) had mild and 8 cases (20%) moderate illness; severe pneumonia and critical disease with acute respiratory distress syndrome were reported in only 3 cases, 2 recovered after; the only patients who died was 69 years old, had cardiac disease, hypertension and diabetes, had undertaken regular rituximab perfusion one month before coronavirus infection and developed pulmonary embolism followed by septic shock.Extreme fatigue was the dominant COVID-19 associated symptom apart from the classical ones including fever, cough, shortness of breath, sore throat, nasal congestion, headache, anosmia and ageusia myalgias and anorexia.No specific pattern for patients requiring intensive care unit admission.Conclusion:The COVID-16 infection rate in patients with inflammatory rheumatic disorders receiving biologics and tsDMARDs is pretty low; although immunosuppressed, these patients seem not to be at risk for severe COVID-19 illness and outcomes. These findings might reflect a potential protective role of certain biologics and/or JAK inhibitors for development and severity of COVID-19 in patients.References:[1]WHO, COVID-19 clinical management, Living Guidance, 25 Jan 2021Disclosure of Interests:CODRINA ANCUTA Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Consultant of: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Cristina Pomirleanu Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Georgiana Strugariu Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Luiza Petrariu Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Eugen Ancuta: None declared, Codruta Bran Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Rodica Chirieac Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Claudia Mihailov Speakers bureau: Abbvie, Pfizer, Lilly, Novartis, Sandoz, Consultant of: Abbvie, Pfizer, Lilly, Novartis, Sandoz

Background:Children born to women with rheumatoid arthritis (RA) have increased incidences of adverse neonatal outcomes and a potential excess risk of specific diseases during childhood and adolescence [1]. Further studies aimed at confirming long-term consequences in the offspring are needed.Objectives:To evaluate whether maternal RA has an impact on the health and developmental outcomes of the offspring.Methods:A retrospective descriptive study was conducted on data regarding 43 children born to mothers diagnosed with either RA or juvenile idiopathic arthritis (JIA) prior to conception. Participants were recruited from several Clinics of Rheumatology located across Romania. Data on neonatal outcomes, lactation, developmental milestones, childhood illnesses, and hospitalizations was collected using a patient-reported questionnaire completed by maternal participants in 2020.Results:Favorable neonatal outcomes were found in 81% of the participants; however, children of mothers with RA had a higher occurrence of favorable outcomes than those with JIA (p = 0.009). Adverse neonatal outcomes reported include the following: small for gestational age (11.6%), intrauterine growth restriction (4.65%), and preterm births (2.75%). There were no incidences of congenital malformations. The mean birth weights of offspring born to mothers with RA are higher than those with JIA (p = 0.00829).While the majority of the children were breastfed (88.4%), those who were not breastfed were hospitalized more often than those who were breastfed for any period of time (p = 0.03). Mothers who experienced a postpartum flare up within the first 4 months breastfed their children significantly less than those who did not have a flare up (14.62 versus 48 weeks, p = 0.00011).The mean age of the children at inclusion was 7.6 ± 5.5 years.Developmental milestones were considered to be within the expected average limits, except for an increased incidence of delayed speech (12%).51.2% of the children were hospitalized at some point during their childhood, with viral enterocolitis, tonsilitis, bronchiolitis, and pneumonia being the most frequently encountered reasons for admission. Surprisingly, children with favorable neonatal outcomes were hospitalized more often than those with unfavorable outcomes (p = 0.0000436). Additionally, children born to mothers under the age of 35 were hospitalized more often than those over 35 (p = 0.02).77.3% of offspring experienced recurrent ear/nose/throat (ENT) infections, 55.8% had allergies, and 39.5% were diagnosed with atopic dermatitis. Childhood allergies were strongly associated with an increased incidence of atopic dermatitis (p = 0.0000585), as was a concurrent maternal thrombophilia diagnosis (p = 0.03).Of the remaining childhood afflictions that were assessed asthma/chronic respiratory diseases (4.65%), juvenile idiopathic arthritis (2.33%), ulcerative colitis (2.33%), diabetes, anxiety/personality disorders, thyroid diseases, febrile seizures, and epilepsy did not yield statistically significant results.Conclusion:Maternal RA was found to be associated with increased incidences of adverse neonatal outcomes, childhood hospitalizations, recurrent ENT infections, allergies, and atopic dermatitis. However, overall health outcomes of offspring did not show alarmingly significant excess morbidities.References:[1]Rom AL, Wu CS, Olsen J, et al. Parental rheumatoid arthritis and long-term child morbidity: a nationwide cohort study. Annals of the Rheumatic Diseases. 2016;75(10):1831–1837. doi:10.1136/annrheumdis-2015-208072Disclosure of Interests:None declared

Background:Recent data have renewed the interest in common pathobiologic pathways in autoimmune rheumatic conditions and periodontal disease, especially on dual impact of innovative anti-rheumatic drugs in modulating both inflammatory and immune articular as well as periodontal damage. Although consistent data about TNF inhibitors and chronic periodontitis are already published, the influence of IL-6 blockade.Objectives:We aimed to explore the influence of weekly subcutaneously IL-6 receptor inhibitor tocilizumab on periodontal health in a local cohort of patients with rheumatoid arthritis (RA) and chronic periodontitis (PD).Methods:We performed a prospective longitudinal 6 months study in 68 patients with moderate-to-severe RA starting tocilizumab (TCZ) in accordance to local recommendations. Extensive rheumatologic (clinical activity, inflammatory, serological biomarkers) and dental (plaque index PI, gingival index GI, bleeding on probing BOP, pocket probing depth PPD, clinical attachment level CAL) assessments were done. Changes in RA activity and periodontal status were reassessed after 3 and 6 months.Results:51 RA and concomitant t of 68 patients in our initial cohort were finally analyzed. Aggressive periodontal disease was reported particularly in disease subsets with excessive inflammatory (serum C reactive protein level) and serologic biomarkers (anti-citrullinated peptide antibodies ACPA). Furthermore, significant correlations between periodontal status, clinical disease activity and ACPA levels were also demonstrated (p 0.05).Conclusion:IL-6 inhibition is able to improve periodontal outcomes in patients with RA and concomitant PD, essentially related to dramatic decrease in serum inflammatory mediators.References:[1]de Molon Scaf, R., Rossa, C.; Thurlings, R.M.; Cirelli, J.A.; Koenders, M.I. Linkage of Periodontitis and Rheumatoid Arthritis: Current Evidence and Potential Biological Interactions, Int. J. Mol. Sci. 2019, 20, 4541.[2]Genco, R.J.; Sanz, M. Clinical and public health implications of periodontal and systemic diseases: An overview. Periodont. 20002020, 83 (1), 08 May.[3]Rinaudo-Gaujous, M.; Blasco-Baque, V.; Miossec, P. et al. Infliximab induced a dissociated response of severe periodontal biomarkers in rheumatoid arthritis patients. J Clin Med2019. 8, 751.[4]Eezammuddeen, N.N.; Vaithilingam, R.D.; Mohamad Hassan, N.H.; Bartold, IL-6 inhibition is able to improve periodontal outcomes in patients with RA and concomitant PD, essentially related to dramatic decrease in serum inflammatory mediators.Disclosure of Interests:CODRINA ANCUTA Speakers bureau: ABBVIE, PFIZER, UCB, NOVARTIS, LILLY, SANDOZ, Consultant of: ABBVIE, PFIZER, UCB, NOVARTIS, LILLY, SANDOZ, EUGEN ANCUTA: None declared, Rodica Chirieac Speakers bureau: ABBVIE, PFIZER, UCB, NOVARTIS, LILLY, SANDOZ, OANA TANCULESCU: None declared, CRISTINA IORDACHE: None declared

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, pConclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly

Background Patients diagnosed with rheumatoid arthritis (RA) before pregnancy may experience a postpartum flare. This event may occur independently of the patient treatment, according to recent guidelines.1 Objectives The aim of this study was to identify possible risk factors of postpartum RA flares. Methods We analysed pregnant RA patients treated with b DMARDs pre-conception/during pregnancy which delivered children. Data analysis was performed in a combined maner : prospectively and retrospectively. Data collection was focused on 5 distinct periods of time: pre-conception, 1 st, 2nd, 3rd pregnancy trimesters, postpartum period before 12 weeks and after 12 weeks. Following parameters were analysed: demographic data (type of pregnancy- planned/unplanned), immunology (RF and ACPA positivity), disease activity score DAS-CRP,2 type of medication and duration. Subfertility status and postpartum flares were registered. The retrospective analysis was represented by interview collected data. Flare was defined as early ( 12 weeks) Results Among 96 pregnant patients, 54 (56%) patients delivered 57 children. Out of 54 patients, 17 (31.5%) were analysed prospectively and 37, 68.5% retrospectively. The patients were exposed to 3 types of b DMARDs: TNF blockers,9 Rituximab5 and Tocilizumab.1Rituximab was stopped before pregnancy in 4 out of 5 patients (1 continued therapy during the 1 st trimester- unplanned pregnancy) and all presented a postpartum flare. Out of 9 patients with TNF blocker therapy, 2 of them stopped the drug before pregnancy and the other 7 used the medication until pregnancy test positivity or until the end of the 2nd trimester. In this group, 6 of 9 patients presented a postpartum flare. One patient was treated with Tocilizumab before pregnancy and experienced an early flare. table 1 presents the analysis of a set of collected parameters. Overall, the majority of the patients (77.8%) experienced a postpartum flare. An early postpartum flare was identified in 53.7% and late one in 24.1%, with a mean value of 11.59±9.45 weeks. The prospective group experienced more frequently an early flare in comparison to group 2 (0.244 (95% CI 0.62–0.965) but without statistic significance. A positive correlation was found between active disease during the 2nd and 3rd trimester and postpartum early flare occurrence (p=0.044). No correlation was found between postpartum flare, fertility status or therapy type and duration. Conclusions RA pregnant patients treated with b DMARDs experience a postpartum flare in the majority of the cases. Persistent active disease during the second and third trimester was identified as a risk factor for postpartum disease flare. Larger prospective studies are neede in order to make a better analysis of all evaluated parameters. References [1] Julia flint et all. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding. Rheumatology2016;55(9). [2] Yael A de Man, Johanna MW Hazes, Fleur E van de Geijn, Catharina Krommenhoek, Radboud JEM Dolhain. Measuring disease activity and functionality during pregnancy in patients with rheumatoid arthritis. Arthritis & Rheumatism57:716–722. doi:10.1002/art.22773 Disclosure of Interest None declared

Background Although widely recognised as extra-articular manifestations of axial spondyloarthritis (axSpA), uveitis developing throughout anti-TNFα treatment is difficult to be classified as disease related or paradoxical event. Objectives We aimed to evaluate the incidence of new onset or relapsing uveitis in patients with axSpA receiving TNF inhibitors. Methods We performed a cross-sectional retrospective study evaluating 126 consecutive active axSpA exposed to TNFα inhibitors according to the local recommendations, followed-up in a single rheumatology department. Patients identified with uveitis were systematically assessed based on a predefined protocol comprising (i) data about uveitis ( de novo or flare; unique episode or recurrence; acute or chronic; anterior, posterior, intermediary or panuveitis; uni or bilateral; outcomes), (ii) responsible medication (drug exposure prior to uveitis, biologic-naive or experimented axSpA, continuation or switching to another biologic) and (iii) rheumatic condition (activity, response to treatment, extra-articular manifestations, disease duration). Results 91 biologic naive axSpA and 35 receiving more than one anti-TNF α were recruited; among them, 318 patient-years exposed to etanercept, 225.37 patient-years to adalimumab, 113.52 patient-years to infliximab, 30.49 patient-years on golimumab. A history of uveitis was found in 27.77% (35 cases). We reported 12 patients developing at least one episode of uveitis during biologic treatment (7 de novo , 10 recurrent uveitis); etanercept was mostly associated with uveitis (8 episodes, 2.51 per 100 patient-years), but also monoclonal antibodies, 3 with golimumab (9.83 per 100 patien-years), 2 under infliximab (1.76 per 100 patien-years), surprisingly, 3 with adalimumab (1.33 per 100 patien-years). Only 3 axSpA had uveitis before starting anti-TNFs. Uveitis was described irrespective of the prior exposure to biologics, mainly in bio-experimented patients, 9 aged between 26 and 72, with disease duration of 6 to 38 years, occurring any-time during biologics (2–116 months). Acute anterior uveitis was commonly reported, only one case of complicated panuveitis. 3 cases (one infliximab, two golimumab) had benefit with switching to another TNF blocker, but in most reported cases uveitis was solved without anti-TNF α interruption. Further, continuation of the same anti-TNF α did not cause relapse in some cases. The underlying SpA was well controlled (ASDAS-CRP) when uveitis, patients being classified as responders compared to previous visit, suggesting paradoxical uveitis. Conclusions Although rare, new onset or flare of uveitis may occur during anti-TNF therapy in axSpA. Surprisingly, not only TNF receptor but also monoclonal antibodies were responsible, etanercept being involved mainly in new onset uveitis. Disclosure of Interest None declared

Background Few small-sized observational studies have suggested that rituximab might be a promising treatment in systemic sclerosis (SSc) Objectives To evaluate the outcomes of SSc-patients receiving in routine care Rituximab Methods Retrospective longitudinal multicenter observational study which included SSc-patients treated with rituximab upon the decision of their physician within the framework of EUSTAR. We interrogated the participating centres and EUSTAR database to determine epidemiological and clinical characteristics, the indication for initiating the treatment, and the following parameters at baseline and at the last visit under treatment: modified Rodnan Skin Score (mRSS), joint, lung and gastrointestinal involvements, treatment, laboratory tests and safety events. Results 248 patients were included: 70 (28%) men, mean age: 51±13 years, mean disease duration: 7±7 years; 150 (65%) had diffuse cutaneous-SSc, 54% were positive for anti-topoisomerase and 71% had lung fibrosis. Overlap disease was noticed in 62 patients (26%) including 23 with rheumatoid arthritis. The indication for the treatment was lung involvement (56%) followed by articular (42%) and skin involvements (30%). At baseline, 175 patients were treated with steroids and 132 with DMARDs. Mean follow-up was 2.4 (±1.9) years. In the whole sample, mRSS decreased from 15±11 to 10±8 (p For SSc-patients treated for lung with baseline FVC In the whole population, 45 patients could stop steroids and mean dose decreased from 10 mg to 7 mg in the other. During the follow-up, 78 (31%) patients had side effects including 35 (14%) with severe side effects leading to discontinuation of the treatment in 10%. Six deaths were recorded (1 heart failure, 1 sepsis, 2 respiratory insufficiencies, 2 sudden deaths). 76 patients had infection, requiring hospitalisation in 20 patients. Conclusions In this study, skin, lung and joint involvement appeared to improve under rituximab. Infections and other severe adverse events were frequently reported. A comparative study including control patients from EUSTAR centres is ongoing. Disclosure of Interest M. Elhai: None declared, O. Distler Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sanofi, Sinoxa and UCB in the area of potential treatments of scleroderma and its complications, V. Smith : None declared, M. Matucci-Cerinic: None declared, J. J. Alegre-Sancho : None declared, M.-E. Truchetet: None declared, Y. Braun-Moscovici: None declared, F. Iannone: None declared, F. Chotchaeva: None declared, A. Lescoat : None declared, E. Siegert : None declared, I. Castellvi: None declared, P. Airo : None declared, S. Vettori: None declared, E. Hachulla: None declared, A. Erler : None declared, L. Ananieva : None declared, M. Krusche: None declared, F. Lopez-Longo : None declared, J. Distler : None declared, N. Hunzelmann : None declared, A.-M. Hoffmann-Vold : None declared, V. Riccieri: None declared, V. Hsu: None declared, M. Pozzi: None declared, C. Ancuta : None declared, E. Rosato : None declared, C. Mihai: None declared, M. Kuwana: None declared, Y. Allanore Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, ChemomAb, Genentech/Roche, Inventiva, Pfizer, Sanofi, Servier, in the area of potential treatments of scleroderma and its complications.

Background Defined as de novo or exacerbation of pathologies that usually responds to biologic agents, paradoxical reactions encompass for a wide spectrum of manifestations (cutaneous, intestinal, ocular) reported during biological therapy (TNF and non-TNF medications) regardless of the underlying rheumatic or non-rheumatic disorder. Objectives To assess drug levels (DL) and anti-drug antibodies (ADA) in patients with paradoxical reactions (de novo or exacerbation of psoriasis, uveitis, Crohn’s disease) induced by biological drugs (bDMARS) in Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Methods We performed a retrospective observational study in cohorts of consecutive RA (267), PSA (65) and AS (145) undergoing TNF (i-TNF) or non-TNF biologics according to the local recommendations for initiation and monitoring, attending a single academic rheumatology department. All patients were assessed at every 24 weeks months for disease activity and outcomes; supplementary, drug immunogenicity (ADA and DL) was systematically evaluated in patients developing paradoxical adverse events. DL and ADA were measured with an ELISA assay and antibody binding test, respectively. Serum drug levels were considered positive for infliximab if >0.035 µg/mL, for adalimumab >0.024 µg/mL, for etanercept >0.035 µg/mL, rituximab >0.75 µg/mL, while the cut-offs for ADA positivity to infliximab was established at 5AU/ml, for adalimumab at 10AU/mL, etanercept at 142 AU/mL, rituximab 140 AU/mL (ELISA, Progenika) Results 42 patients with paradoxical psoriasis (30 with de novo lesions, 18 with palmo-plantar pustulosis, 12 with exacerbation of pre-existent lesions), 12 with paradoxical uveitis (5 with a new onset uveitis) and 3 with paradoxical Crohn’s were included in the final analysis. Paradoxical events related to abatacept, certolizumab (one de novo psoriasis per agent) or golimumab (2 new onset uveitis, one flare of Chron’s disease) were excluded from the final analysis as no immunogenicity lab tests were provided. Drug induced paradoxical events were described not only with all TNF inhibitors but also with rituximab. DL was in normal range in all these patients; in addition, ADA were either negative, or, if present, had no impact on drug concentration. Furthermore, we found no significant differences in drug levels of TNF inhibitors for RA, PsA and AS. Moreover, no statistical significant differences were observed in the detection of ADA between the three groups. Conclusions Patients who develop either true or borderline paradoxical AE have adequate drug levels, with normal ADA concentrations. Disclosure of Interest None declared

Biological drugs (bDMARDs) have changed landscape and outcomes in various rheumatic conditions. Increased risk for infections, paradoxical reactions, autoimmunogenicity are widely acknowledged and may be responsible for treatment failure and switching among biologics. Objective To assess drug-induced autoimmunity (serology, clinical significance) in patients with rheumatoid arthritis (RA) treated with bDMARDs. Patients and methods Longitudinal observational study in 246 bionaive RA receiving their first bDMARD, anti-tumour necrosis factor (TNF) or non-TNF drugs, according to local treatment guidelines. Disease activity, therapeutic response and serial autoantibody profiles (antinuclear (ANA), anti-dsDNA) were systematically assessed at baseline and every six months. Prevalence, clinical significance and therapeutic implications of ANA/anti-dsDNA specificities were further analysed (SPSS-19, p Results 214 RA received TNF inhibitors (56 infliximab, 65 adalimumab, 8 golimumab, 18 certolizumab, 67 etanercept) as first bDMADs and 32 different mechanism of action (10 rituximab, 7 abatacept, 15 tocilizumab). Overall, ANA seroconversion was demonstrated in 14.22% (35/246), while anti-dsDNA in 8.94% (22/246); no change in the immunological profile under golimumab, certolizumab, abatacept or rituximab. Significantly higher rates of ANA were reported in infliximab-treated RA (30.53%) as compared to adalimumab (18.46%), etanercept (7.46%) and tocilizumab (6.66) (p ANA/anti-dsDNA positive status correlated with RA activity (DAS28-ESR) and loss of therapeutic response, concomitant DMARDs (leflunomide) and corticosteroids, administration adverse reactions (p Only four patients (1.62%; 4/246) were classified as drug-induced lupus. Three of them (infliximab, adalimumab, tocilizumab –induced) developed mild to moderate disease, with characteristic malar rash, serositis, haematological, elevated ANA and anti-dsDNA that normalised six months after bDMARD discontinuation; the fourth patient had adalimumab-induced lupus two months after drug initiation, with severe course (subacute extensive skin lesions, cytopenia, serositis) and fatal outcome. Conclusions Development of ANA with or without anti-dsDNA specificity is typically associated with loss of response to bDMARD in RA and infrequently responsible for drug-induced lupus. Systematic evaluation of ANA/dsDNA is not recommended in routine practice, but essential in certain specific clinical settings (secondary non-responders or lupus-like symptoms).

Despite major achievements in understanding the pathobiology and management of Systemic Lupus Erythematosus (SLE), cardio-vascular burden remains a complex challenge in routine practice. Echocardiography emerges as a valuable non-invasive technique widely recommended for the screening, evaluation and monitoring of cardiac involvement in different SLE settings. Objectives to evaluate the prevalence and nature of the clinical and subclinical cardiac involvement in SLE, and to identify potential relation with several disease-related parameters. Design and methods Retrospective observational study in 120 consecutive SLE (fulfilling either 1987 ACR or new 2012 SLICC/ACR criteria), mean age 36.9+15.2 years and mean disease duration 9.2+8.5 years, attending the outpatient rheumatology department at least once. Demographic, clinical, immunologic profile, disease activity (SLEDAI), organ damage (SLICC/ACR) data were collected. Patients were assessed according to a standardised protocol focused on clinical, immunologic profile, disease activity (SLEDAI), severity and organ damage (SLICC/ACR); cardiac involvement (valve damage, systolic and diastolic dysfunction, pericardial disease, myocardial ischemia, pulmonary hypertension) was evaluated by 2D transthoracic echocardiography (TTE). Statistical analysis was done in SPSS, p Results Valvular disease was reported in 61.98% SLE (14% stenosis, 20.66% valvular masses, 33% mild-to- moderate regurgitation, 34.73% leaflet thickening. Libman-Sacks endocarditis was not depicted. Asymptomatic decrease in left ventricular ejection fraction (55%) was described in 16.52%, the lowest LVEF being 33% in 4.13% patients; statistical significant negative correlation LVEF – disease duration and activity (p 0.05). Global hypokinesis on TTE as an indicator of subclincal myocarditis was demonstrated in up to one third SLE, while cardiomyopathy in one fourth. Mild pericardial effusion is observed in 31.2% cases, while cardiac tamponade in 4 cases; pericardial thickening was reported in 38% SLE. Finally, abnormal systolic pressure in pulmonary artery was found in 24.79% patients. Conclusion Patients with SLE are at increased risk to develop either clinical or subclinical cardiovascular manifestations as demonstrated by echocardiographic studies. A systematic TTE assessment is routinely recommended for the screening and monitoring of cardiac events.

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (S.D.) HAQ-DI 1.1 (0.83)], with ‘grip’ and ‘activity’ being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = −0.53, P < 0.0001).Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.