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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.

Background: Glucocorticoid exposure is a significant driver of morbidity in children with systemic juvenile idiopathic arthritis (sJIA). We determined the effect of early initiation of biologic therapy (IL-1 or IL-6 inhibition) on glucocorticoid exposure in hospitalized patients with new-onset sJIA. Methods: We emulated a pragmatic sequence of trials (“pseudo-trials”) of biologic initiation in children (≤ 18 years) hospitalized with new-onset sJIA utilizing retrospective data from an administrative database from 52 tertiary care children’s hospitals from 2008 to 2019. Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial. Patients in the source population could meet eligibility criteria at several timepoints. Mixed-effects logistic regression was used to determine the effect of biologic initiation on in-hospital glucocorticoid exposure. Results: Four hundred sixty-eight children met eligibility criteria, of which 19% received biologic therapy without preceding or concomitant initiation of immunomodulatory medications. This proportion significantly increased over time during the study period (p < 0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1380 assigned to the non-biologic arm. After adjustment, there was a trend toward decreased odds of glucocorticoid initiation in the biologic arm compared to the non-biologic arm (OR 0.39, 95% CI [0.13, 1.15]). Conclusion: Biologic initiation in children hospitalized with new-onset sJIA significantly increased over time and may be associated with reduced glucocorticoid exposure. The increasing use of first-line biologic therapy may lead to clinically relevant reductions in treatment-related adverse effects of glucocorticoid-reliant therapeutic approaches.

Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. Subjects and methods: The GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with ≥1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL). Results: We randomised 451 patients with established RA and mean 2.1 comorbidities, age 72, disease duration 11 years and DAS28 4.5. 79% were on disease-modifying treatment, including 14% on biologics. 63% prednisolone versus 61% placebo patients completed the trial. Discontinuations were for AE (both, 14%), active disease (3 vs 4%) and for other (including covid pandemic-related disease) reasons (19 vs 21%); mean time in study was 19 months. Disease activity was 0.37 points lower on prednisolone (95% CL 0.23, p < 0.0001); joint damage progression was 1.7 points lower (95% CL 0.7, p = 0.003). 60% versus 49% of patients experienced the harm outcome, adjusted relative risk 1.24 (95% CL 1.04, p = 0.02), with the largest contrast in (mostly non-severe) infections. Other GC-specific events were rare. Conclusion: Add-on low-dose prednisolone has beneficial long-term effects in senior patients with established RA, with a trade-off of 24% increase in patients with mostly non-severe AE; this suggests a favourable balance of benefit and harm. Trial registration number: NCT02585258.

Objectives: Rheumatoid arthritis (RA), along with glucocorticoid use, is associated with cardiovascular disease. Cardiovascular safety of glucocorticoids in RA is controversial and may be related to dose and duration of use. We determined if initiating glucocorticoids in steroid-naive RA patients would increase cardiovascular event (CVE) risk in a dose and duration-dependent manner over short-term intervals. Methods: Patients enrolled in CorEvitas (formerly Corrona) RA registry. Cox proportional-hazards models estimated adjusted HRs (aHR) for incident CVE in patients who initiated glucocorticoid treatment, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates: Clinical Disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use. Glucocorticoid use assessed current daily dose, cumulative dose and duration of use over rolling intervals of preceding 6 months and 1 year. Results: 19 902 patients met criteria. 1106 CVE occurred (1.66/100 person-years). Increased aHR occurred at current doses of ≥5–9 mg 1.56 (1.18–2.06) and ≥10 mg 1.91 (1.31–2.79), without increased risk at 0–4 mg 1.04 (0.55–1.59). Cumulative dose over preceding 6 months showed increased aHR at 751–1100 mg 1.43 (1.04–1.98) and >1100 mg 2.05 (1.42–2.94), without increased risk at lower doses; duration of use over preceding 6 months exhibited increased aHR for >81 days of use 1.54 (1.08–2.32), without increased risk at shorter durations. One-year analyses were consistent. Conclusions:Over preceding 6-month and 1-year intervals, initiating glucocorticoids in steroid-naïve RA patients is associated with increased risk of CVE at daily doses ≥5 mg and increased cumulative dose and duration of use. No association with risk for CVE was found with daily prednisone of ≤4 mg or shorter cumulative doses and durations.

ObjectivesPatient-reported outcome measures (PROMs) are important for clinical practice and research. Given the high unmet need, our aim was to develop a comprehensive PROM for systemic sclerosis (SSc), jointly with patient experts.MethodsThis European Alliance of Associations for Rheumatology (EULAR)-endorsed project involved 11 European SSc centres. Relevant health dimensions were chosen and prioritised by patients. The resulting Systemic Sclerosis Impact of Disease (ScleroID) questionnaire was subsequently weighted and validated by Outcome Measures in Rheumatology criteria in an observational cohort study, cross-sectionally and longitudinally. As comparators, SSc-Health Assessment Questionnaire (HAQ), EuroQol Five Dimensional (EQ-5D), Short Form-36 (SF-36) were included.ResultsInitially, 17 health dimensions were selected and prioritised. The top 10 health dimensions were selected for the ScleroID questionnaire. Importantly, Raynaud’s phenomenon, impaired hand function, pain and fatigue had the highest patient-reported disease impact. The validation cohort study included 472 patients with a baseline visit, from which 109 had a test–retest reliability visit and 113 had a follow-up visit (85% female, 38% diffuse SSc, mean age 58 years, mean disease duration 9 years). The total ScleroID score showed strong Pearson correlation coefficients with comparators (SSc-HAQ, 0.73; Patient’s global assessment, Visual Analogue Scale 0.77; HAQ-Disability Index, 0.62; SF-36 physical score, −0.62; each pConclusionsWe have developed and validated the EULAR ScleroID, which is a novel, brief, disease-specific, patient-derived, disease impact PROM, suitable for research and clinical use in SSc.

OBJECTIVE Expression of dipeptidylpeptidase 4 (DPP-4) identifies a dermal fibroblast lineage involved in scarring during wound healing. The role of DDP-4 in tissue fibrosis is, however, unknown. The aim of the present study was to evaluate DPP-4 as a potential target for the treatment of fibrosis in patients with systemic sclerosis (SSc). METHODS Expression of DPP-4 in skin biopsy samples and dermal fibroblasts was analyzed by real-time polymerase chain reaction, immunofluorescence, and Western blot analyses. The activity of DPP-4 was modulated by overexpression, knockdown, and pharmacologic inhibition of DPP4 using sitagliptin and vildagliptin. The effects of DPP4 inhibition were analyzed in human dermal fibroblasts and in different mouse models of SSc (each n = 6). RESULTS The expression of DPP-4 and the number of DPP-4-positive fibroblasts were increased in the fibrotic skin of SSc patients, in a transforming growth factor β (TGFβ)-dependent manner. DPP-4-positive fibroblasts expressed higher levels of myofibroblast markers and collagen (each P < 0.001 versus healthy controls). Overexpression of DPP4 promoted fibroblast activation, whereas pharmacologic inhibition or genetic inactivation of DPP4 reduced the proliferation, migration, and expression of contractile proteins and release of collagen (each P < 0.001 versus control mice) by interfering with TGFβ-induced ERK signaling. DPP4-knockout mice were less sensitive to bleomycin-induced dermal and pulmonary fibrosis (P < 0.0001 versus wild-type controls). Treatment with DPP4 inhibitors promoted regression of fibrosis in mice that had received bleomycin challenge and mice with chronic graft-versus-host disease, and ameliorated fibrosis in TSK1 mice (each P < 0.001 versus untreated controls). These antifibrotic effects were associated with a reduction in inflammation. CONCLUSION DPP-4 characterizes a population of activated fibroblasts and shows that DPP-4 regulates TGFβ-induced fibroblast activation in the fibrotic skin of SSc patients. Inhibition of DPP4 exerts potent antifibrotic effects when administered in well-tolerated doses. As DPP4 inhibitors are already in clinical use for diabetes, these results may have direct translational implications for the treatment of fibrosis in patients with SSc.

Objective: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. Methods: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. Results: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC = 0.869), MRI (AUC = 0.885) or C-reactive protein (AUC = 0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC = 0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. Conclusions: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.

Systemic sclerosis (SSc) is a rare disease, with unfavorable clinical course and prognosis, characterized by progressive multisystemic involvement. SSc associated pulmonary hypertension (SSc-PAH) and interstitial lung disease (ILD) are the most important factors for morbi-mortality in these patients, being responsible for more than 60% of total deaths. Though pulmonary arterial hypertension (PAH) is the dominant subtype seen in SSc, PH secondary to ILD, left-heart pathology, and pulmonary veno-occlusive disease (PVOD) are also possible occurrences. Initial evaluation of a SSc case is complex and should be performed with a multidisciplinary approach. Early detection of SSc-PAH is imperative, given the fact that new and effective medications are available and early treatment was shown to improve outcomes. Therefore, screening algorithms must be used adequately and in a cost-effective manner. Sensitivity and negative predictive value (NPV) are the most important performance measures in a screening test. Several algorithms were developed in the last decade (e.g., DETECT and ASIG) and demonstrated higher efficiency when compared to older algorithms. The present manuscript details the risk factors for SSc-PAH and includes a critical description of current detection algorithms, as a primer for clinicians working in the field of cardio-rheumatology.

Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, characterized by multisystemic involvement and a potentially severe evolution. Pulmonary arterial hypertension (PAH) is a rare complication of SLE, with low 5-year survival. Case presentation. We are presenting the case of a female patient, aged 56 years old, diagnosed in 1992 with SLE with cutaneous manifestations (butterfly-shaped erythematous rash), joint manifestations (polyarthritis), serositis manifestations (massive pleuropericarditis), and immunological manifestations (positive anti-dsDNA antibodies, decreased C3), ignored therapeutically for a long time. In 2010 she complained of dyspnea on medium exertion and leg edemas, with marked increase of PAPs by echocardiography. She was diagnosed with severe PAH (confirmed by right heart catheterization) and in the “Marius Nasta” National Institute of Pneumology she started a treatment with an endothelin receptor antagonist (Bosentan) in combination with a prostacyclin receptor agonist (Selexipag). Since 2013 the patient is on oral anticoagulant treatment for permanent atrial fibrillation. In 2015 she was referred back to out clinic as she complained of recurrent episodes of massive ascites with evacuatory paracenteses in amounts of about 6-9L per paracentesis. After excluding other causes, ascites was considered to be secondary to the SLE, and a treatment was initiated with Hydroxychloroquine (HCQ) and pulse therapy with Methylprednisolone, on which the remission of the ascites was achieved during the following months. Currently, the SLE is well controlled without recurrence of ascites on treatment with HCQ and gradual decrease until stopping of cortisone doses, and the PAH is stable. Conclusion. PAH is a rare complication of the SLE, with a complex pathophysiological immune mechanism, for which - together with the specific vasodilator treatment - the increase of immune suppression is recommended.

Background and objectives The University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) is validated to capture gastrointestinal (GI) tract morbidity in patients with systemic sclerosis (SSc). The aims of this study were to determine in a large SSc cohort if the UCLA GIT 2.0 is able to discriminate patients for whom a rheumatologist with experience in SSc would recommend an esophago-gastro-duodenoscopy (EGD), and if it could identify patients with endoscopically proven esophagitis or with any pathologic finding on EGD. Methods We selected patients fulfilling the ACR/EULAR 2013 criteria for SSc from our EUSTAR center having completed at least once the UCLA GIT 2.0 questionnaire, and we collected data on gastrointestinal symptoms and EGD from their medical charts. We analyzed by general linear mixed effect models several parameters, including UCLA GIT 2.0, considered as potentially associated with the indication of EGD, as well as with endoscopic esophagitis and any pathologic finding on EGD. Results We identified 346 patients (82.7% female, median age 63 years, median disease duration 10 years, 23% diffuse cutaneous SSc) satisfying the inclusion criteria, who completed UCLA GIT 2.0 questionnaires at 940 visits. EGD was recommended at 169 visits. In multivariable analysis, UCLA GIT 2.0 and some of its subscales (reflux, distention/bloating, social functioning) were associated with the indication of EGD. In 177 EGD performed in 145 patients, neither the total ULCA GIT 2.0 score nor any of its subscales were associated with endoscopic esophagitis, nor with any pathologic EGD findings. Conclusions In a real-life setting, the UCLA GIT 2.0 and its reflux subscale were able to discriminate patients with SSc who had an indication for EGD, but did not correlate with findings in EGD. We conclude that, while using the UCLA GIT 2.0 in the routine care of patients with SSc may help the rheumatologist to better understand the burden of GI symptoms in the individual patient, it should not be used as a stand-alone instrument to identify an indication of EGD.

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.

BACKGROUND Travel to clinics for chronic wound management is burdensome to patients. Remote assessment and management of wounds using mobile and telehealth approaches can reduce this burden and improve patient outcomes. An essential step in wound documentation is the capture of wound images, but poor image quality can have a negative influence on the reliability of the assessment. To date, no study has investigated the quality of remotely acquired wound images and whether these are suitable for wound self-management and telemedical interpretation of wound status. OBJECTIVE Our goal was to develop a mobile health (mHealth) tool for the remote self-assessment of digital ulcers (DUs) in patients with systemic sclerosis (SSc). We aimed to define and validate objective measures for assessing the image quality, evaluate whether an automated feedback feature based on real-time assessment of image quality improves the overall quality of acquired wound images, and evaluate the feasibility of deploying the mHealth tool for home-based chronic wound self-monitoring by patients with SSc. METHODS We developed an mHealth tool composed of a wound imaging and management app, a custom color reference sticker, and a smartphone holder. We introduced 2 objective image quality parameters based on the sharpness and presence of the color checker to assess the quality of the image during acquisition and enable a quality feedback mechanism in an advanced version of the app. We randomly assigned patients with SSc and DU to the 2 device groups (basic and feedback) to self-document their DU at home over 8 weeks. The color checker detection ratio (CCDR) and color checker sharpness (CCS) were compared between the 2 groups. We evaluated the feasibility of the mHealth tool by analyzing the usability feedback from questionnaires, user behavior and timings, and the overall quality of the wound images. RESULTS A total of 21 patients were enrolled, of which 15 patients were included in the image quality analysis. The average CCDR was 0.96 (191/199) in the feedback group and 0.86 (158/183) in the basic group. The feedback group showed significantly higher (P CONCLUSIONS We developed an mHealth tool that enables patients with SSc to acquire good-quality DU images and demonstrated that it is feasible to deploy such an app in this patient group. The feedback mechanism improved the overall image quality. The introduced technical solutions consist of a further step towards reliable and trustworthy digital health for home-based self-management of wounds.

Contains fulltext : 238184.pdf (Publisher’s version ) (Closed access) Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.

Muscle involvement in systemic sclerosis (SSc) incorporates a large spectrum of clinical pictures, from mild forms with mild proximal muscle weakness and no or slight elevation of muscle enzymes and no evidence of myositis in magnetic resonance imaging (MRI) or muscle biopsy findings, to typical overt polymyositis, sometimes also associating cardiac involvement with myocarditis. Due to lack of classification criteria and treatment recommendations, the therapy of SSc-related myopathies remains challenging.

Capillary density on nailfold capillaroscopy (NFC) is considered a promising instrument for assessing disease characteristics in patients with systemic sclerosis (SSc), however, there is no agreement yet over how to analyze and interpret the results. The objective of this study was to investigate the possible associations of the mean number of capillaries with disease characteristics, disease activity [measured by the European Scleroderma Study Group (EScSG) disease activity score] and survival in a single-center cohort of patients with SSc. Sixty-eight patients were included; 54 had follow-up at 6 months. Thirty-two images per patient were assessed independently by two raters, scoring the mean number of capillaries in all fingers (N), in the 3rd finger of the dominant hand (dN(3)) and in the 4th finger of the non-dominant hand (ndN(4)) for each patient. NFC ‘early’, ‘active’ and ‘late’ patterns were also assessed. Two thousand and seventy-six images were scored at baseline, 1,728 at follow-up. Baseline N was median (IQR) 5.1 (2.7) for rater 1, and 4.9 (1.7) for rater 2, respectively. N was significantly lower in patients with a history of digital ulcers (DUs), vs. those who never had DUs 4.8 (1.4) vs. 6.4 (3.1), P=0.016. A lower N was associated with higher disease activity at baseline and follow-up (linear regression adjusted for age, sex and history of DUs). A lower ndN(4) was associated with increased mortality (logistic regression adjusted for age and sex). In conclusion, in patients with SSc, a lower mean number of capillaries assessed by NFC was associated with higher disease activity after 6 months of follow-up and with shorter survival.

To evaluate the therapeutic benefit of botulinum toxin A (BTX-A) injections for digital ulcers (DU) in patients with systemic sclerosis (SSc).A systematic literature review was performed and the identified articles were selected by two reviewers and analysed with respect to date of publication, inclusion and exclusion criteria, number and age of participants, volume of BTX-A, injection sites, outcomes, and adverse events. In addition, in the Zurich cohort, 7 SSc patients were eligible for the study and were assessed for the duration of DU to heal, duration of DU-free periods, changes in frequency and numbers of prescribed vasodilators, pain and blood flow.In five articles from the systematic review, at least 48% of DU had healed and up to 100% reduction in VAS for pain was reported. Our 7 patients (median age of 53 (47-82) years) had in median 2.5 (2-4) DU and were injected with a median BTX-A volume of 90 (50-100) units per hand. Of the 31 DU in all patients, 77% (n=24) healed. Time to wound closure was in median 8 (4-12) weeks and the DU-free duration was in median 8 (3-10) months. In 80% of the cases, at least one vasodilator was stopped or could be administered less frequently. An improvement of blood flow and pain was reported in 60% of the cases.BTX-A injections might be of benefit for the treatment of chronic, refractory DU in selected SSc patients, yet a sufficiently powered prospective study will be needed as ultimate proof.

Systemic sclerosis (SSc) is a chronic immune-mediated connective tissue disease with heterogeneous organ involvement. New classification criteria were developed allowing disease identification even before the onset of its hallmark, skin fibrosis. Incidence and prevalence vary among reports and are influenced by methodology. Despite earlier diagnosis, mortality of SSc is still considerable, mainly because of cardiopulmonary causes. Genetic predisposition is entangled and implies genes of the major histocompatibility complex and also other loci related to immune regulation. Known environmental risk factor is exposure to organic solvents and silica, but no single risk factor has emerged. Disease outcome measures including patient-reported outcomes have been proposed and validated, and their use is expected to contribute to measure treatment response in clinical trials. Because of the low frequencies and the high heterogeneity of the disease, large multicenter research collaborations are envisaged to achieve advancement in SSc management.

ObjectivePulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc). In this longitudinal study, we aimed to identify factors associated with an unfavourable outcome in patients with SSc with early PAH (SSc-PAH) from the DETECT cohort.MethodsPatients with SSc-PAH enrolled in DETECT were observed for up to 3 years. Associations between cross-sectional variables and disease progression (defined as the occurrence of any of the following events: WHO Functional Class worsening, combination therapy for PAH, hospitalisation or death) were analysed by univariable logistic regression.ResultsOf 57 patients with PAH (median observation time 12.6 months), 25 (43.9%) had disease progression. The following factors (OR (95% CI)) were associated with disease progression: male gender (4.1 (1.2 to 14.1)), high forced vital capacity % predicted/carbon monoxide lung diffusion capacity (DLCO)% predicted ratio (3.6 (1.2 to 10.7)), high Borg Dyspnoea Index (1.7 (1.1 to 2.6)) and low DLCO% predicted (non-linear relationship).ConclusionMore than 40% of early-diagnosed patients with SSc-PAH had disease progression during a short follow-up time, with male gender, functional capacity and pulmonary function tests at PAH diagnosis being associated with progression. This suggests that even mild PAH should be considered a high-risk complication of SSc.

Background. Semi-quantitative nailfold capillaroscopy (NFC) scoring represents a promising tool for assessing disease activity, severity and change in systemic sclerosis (SSc), however there is no consensus yet over which capillaroscopy abnormalities should be analyzed and how. Objective. Investigation of the reliability of the qualitative and semi-quantitative scoring of NFC assessment between two raters and test-retest for each rater in a SSc cohort. Methods. This is a single-center pilot study where 2 raters assessed the NFC images of 48 consecutive patients with SSc. Data were analyzed in 3 ways: 1. qualitatively by “normal”/“abnormal” category; 2. qualitatively by the following categories: “early”, “active”, “late” SSc patterns, “normal”, and unclassifiable in any pattern, and step; 3. Semi-quantitatively by calculating the mean score for capillary loss, disorganization of the microvascular array, giant capillaries, microhaemorrhages and capillary ramifications and combinations of giant capillaries and microhaemorrhages (as a surrogate for vascular activity). Disorganization and ramifications (surrogate for vascular damage) were also assessed. Variables for all steps were calculated for all fingers and for each finger. Inter-rater/intra-rater agreement was assessed by Cohen’s kappa coefficients for qualitative variables and by intraclass correlation coefficients (ICC) for mean score values of abnormalities. Results. Inter-rater reliability ranged from good to excellent agreement for mean score values of abnormalities in all fingers (ICC coefficients 0.745 to 0.897) and was excellent for activity (ICC coefficient of 0.923) and damage combinations (ICC coefficient of 0.918). Assessment of abnormalities in a qualitative manner (normal/abnormal or with capillaroscopy patterns) showed weaker inter-rater agreement than the semi-quantitative assessment (k coefficient

Systemic sclerosis (SSc) is a chronic autoimmune disease causing complex hand disability. A reliable tool for hand function assessment in SSc is the Cochin Hand Functional Disability Scale (CHFS). More recently, a short-form CHFS of 6 items (CHFS-6) has been developed. Objectives To validate the CHFS and the new CHFS-6 in Romanian patients with SSc. Patients and methods Consecutive patients with SSc who completed the CHFS were included. All patients were assessed according to the recommendations of the European Scleroderma and Research Trials and also completed the Scleroderma Health Assessment Questionnaire and the Hand Mobility in Scleroderma questionnaire. Finger range-of-motion distances were measured. Results Seventy patients, 63 female and 7 male patients (age median, 53.0 years; interquartile range [IQR], 21.0 years), were included. Twenty seven had diffuse cutaneous involvement (dcSSc). Median CHFS and CHFS-6 at baseline were 25.0 (IQR, 37.0) and 8.0 (IQR, 13.0), respectively.The internal consistency (Cronbach α = 0.96, respectively, 0.90, in all 70 patients) and test-retest reliability (intraclass correlation coefficient = 0.98 for both, in 38 patients) of both CHFS and CHFS-6 were excellent. The CHFS-6 had a very high correlation with the CHFS. There were moderate to good correlations with Hand Mobility in Scleroderma, Scleroderma Health Assessment Questionnaire, and the anthropometric measurements (construct validity). In patients with early dcSSc with a second evaluation, we found good to moderate sensitivity to change (standardized response mean of 0.8 and effect size of 0.4 for CHFS, and standardized response mean of 1.1 and effect size of 0.6 for CHFS-6). Conclusions The CHFS and CHFS-6 are valid and easy-to-use tools for hand involvement in SSc, which can be used in clinical or research setting.

BackgroundThe European Scleroderma Trials and Research Group (EUSTAR) recently developed a preliminarily revised activity index (AI) that performed better than the European Scleroderma Study Group Activity Index (EScSG-AI) in systemic sclerosis (SSc).ObjectiveTo assess the predictive value for short-term disease severity accrual of the EUSTAR-AI, as compared with those of the EScSG-AI and of known adverse prognostic factors.MethodsPatients with SSc from the EUSTAR database with a disease duration from the onset of the first non-Raynaud sign/symptom ≤5 years and a baseline visit between 2003 and 2014 were first extracted. To capture the disease activity variations over time, EUSTAR-AI and EScSG-AI adjusted means were calculated. The primary outcome was disease progression defined as a Δ≥1 in the Medsger’s severity score and in distinct items at the 2-year follow-up visit. Logistic regression analysis was carried out to identify predictive factors.Results549 patients were enrolled. At multivariate analysis, the EUSTAR-AI adjusted mean was the only predictor of any severity accrual and of that of lung and heart, skin and peripheral vascular disease over 2 years.ConclusionThe adjusted mean EUSTAR-AI has the best predictive value for disease progression and development of severe organ involvement over time in SSc.

ObjectivesTo investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) Methods601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5–4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed.ResultsDuring 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF ConclusionsThe present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

Objectives. To identify from a patient's perspective, difficulties and differences in the comprehension of five global presenteeism measures in patients with inflammatory arthritis and OA across seven countries. Methods. Seventy patients with a diagnosis of inflammatory arthritis or OA in paid employment were recruited from seven countries across Europe and Canada. Patients were randomly allocated to be cognitively debriefed on 3/5 global measures [Work Productivity Scale - Rheumatoid Arthritis, Work Productivity and Activity Impairment Questionnaire (WPAI), Work Ability Index, Quality and Quantity questionnaire, and WHO Health and Work Performance Questionnaire (HPQ)], with the WPAI debriefed in all patients as a standard measure of comparison between countries and patients. NVivo was used to code the data into four themes: construct and anchor, time recall, reference frame, and attribution. Results. Discrepancies were found in the interpretation of the word performance (HPQ) between countries, with Romania and Sweden relating performance to sports rather than work. Seventy percent of patients considered that a 7-day recall (WPAI) can accurately represent how their disease affects work productivity. The compared to normal reference (Quality and Quantity questionnaire) was reportedly too ambiguous, and the comparison with colleagues (HPQ), made many feel uncomfortable. Overall, 29% of patients said the WPAI was the most relevant to them, making it the most favoured measure. Conclusion. Overall, patients across countries agree that the construct of work productivity in the last 7 days can accurately reflect the impact of disease while at work. Some current constructs to assess at-work productivity are not interchangeable between languages.

Introduction. The relationship between periodontal disease (PD) and rheumatoid arthritis (RA) is currently only partially known, both being chronic multifactorial diseases that may share common pathogenic mechanisms and etiological factors. In a previous meta-analysis we concluded that patients with RA are more commonly affected by PD and develop more severe forms of the disease, compared to the general population. Objectives. The current study aimed to assess the degree of periodontal damage and oral hygiene on a group of patients diagnosed with RA. Methods. The study was conducted on a group of 30 patients, 6 sextants being assessed in each patient (180 potentially evaluable sextants). Establishing the degree of periodontal damage and oral hygiene was achieved by determining the Community Periodontal Index of Treatment Needs (CPITN) and Oral Hygiene Index (IHB, also known as OHI). Results. The mean CPITN score/sextant was 1.92. After clinical examination we found 10 edentulous sextants that could not be evaluated. As a result of the distribution of the scores on all the 170 evaluable sextants, we obtained: CPITN 0 – 11.1%, CPITN 1 – 23.6%, CPITN 2 – 32.4%, CPITN 3 – 27.6%, CPITN 4 – 5.3%. After analyzing the oral hygiene index the mean value we found was 16. Distribution of IHB intervals was: IHB 0-12 (40%), IHB 13-24 (53.3%), IHB 25-36 (6.6%). Discussion and conclusions. Comparing our results to data from the literature, in our group of patients with RA the only CPITN index criteria significantly increased, compared to the healthy population, were gingival bleeding on probing and the number of periodontal pockets with 4-5.5 mm depth.

Objective.Several global measures to assess at-work productivity loss or presenteeism in patients with rheumatic diseases have been proposed, but the comparative validity is hampered by the lack of data on test-retest reliability and comparative concurrent and construct validity. Our objective was to test-retest 5 global measures of presenteeism and to compare the association between these scales and health-related well-being.Methods.Sixty-five participants with inflammatory arthritis or osteoarthritis in paid employment were recruited from 7 countries (UK, Canada, Netherlands, France, Sweden, Romania, and Italy). At baseline and 2 weeks later, 5 global measures of presenteeism were evaluated: the Work Productivity Scale–Rheumatoid Arthritis (WPS-RA), Work Productivity and Activity Impairment Questionnaire (WPAI), Work Ability Index (WAI), Quality and Quantity questionnaire (QQ), and the WHO Health and Performance Questionnaire (HPQ). Agreement between the 2 timepoints was assessed using single-measure intraclass correlations (ICC) and correlated between each other and with visual analog scale general well-being scores at followup by Spearman correlation.Results.ICC between measures ranged from fair (HPQ 0.59) to excellent (WPS-RA 0.78). Spearman correlations between measures were moderate (Qquality vs WAI, r = 0.51) to strong (WPS-RA vs WPAI, r = 0.88). Correlations between measures and general well-being were low to moderate, ranging from −0.44 ≤ r ≤ 0.66.Conclusion.Test-retest results of 4 out of 5 global measures were good, and the correlations between these were moderate. The latter probably reflect differences in the concepts, recall periods, and references used in the measures, which implies that some measures are probably not interchangeable.

Background:Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, with increased morbidity and mortality, often diagnosed in advanced stages. The recently published 2019 American College Of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SLE are weighted, hierarchically clustered criteria developed to increase reliability and the identification of early SLE.Objectives:To compare the sensitivity and specificity of the 2019 ACR/EULAR criteria with the 2012 SLICC criteria in a large single-centre cohort of patients with SLE, diagnosed according to expert oppinion.Methods:Data of SLE patients evaluated in our centre between 1996-2019 have been retrospectively analyzed. The control cohort included patients with positive antinuclear antibodies of other ethiology than SLE, evaluated between 2001-2019. The sensitivity and specificity of the 2019 ACR/EULAR and 2012 SLICC criteria were tested using the McNemar test for correlated proportions.Results:Four hundred and forty-six patients with SLE (413 women, mean±SD age 40.5±12.7 years, disease duration 10.1±9.2 years) and 67 controls (63 women, mean±SD age 50.4±12.6 years, disease duration 7.6±6.9 years; 29 systemic sclerosis (SSc), 18 mixed connective tissue dissease (MCTD), 15 undifferentiated CTD, 2 rheumatoid arthritis (RA), 2 SSc – RA overlaps and 1 dermatomyositis) were included. The sensitivity of the 2019 ACR/EULAR and 2012 SLICC criteria were similar 85.4% and 83.6 %, respectively (p=0.3). The specificity of the 2019 ACR/EULAR and 2012 SLICC criteria were 70.2 % and 86.6%, respectively (p=0.007). In the SLE group, patients missclassified according to the new 2019 ACR/EULAR criteria were 65, whereas according to the 2012 SLICC criteria were 73; of them, 44 patients did not fulfill any criteria. In the control group, patients misclassified had mainly MCTD (13/20 patients according to the new 2019 ACR/EULAR, and 8/9 according to the 2012 SLICC criteria).Conclusion:In this real-life cohort, the 2019 ACR/EULAR criteria have a similar sensitivity and lower specificity than the 2012 SLICC criteria, misclassifying especially MCTD patients. These results might be due to the long disease duration in our cohort.References:[1] Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400–1412. doi:10.1002/art.40930Disclosure of Interests:None declared

Background Worker productivity loss, including presenteeism, is an important outcome for patients with inflammatory (IA) diseases and osteoarthritis (OA) and is frequently seen as a health outcome in clinical studies. It is important to understand which factors are related with this patient reported outcome in order to inform future work related interventions. Objectives To assess the association between disease related, psychological and work related factors with presenteeism. Methods In a large international study evaluating measures of presenteeism we recruited patients with IA and OA from UK, Fr, NL, Es, Se, Ro, It, Pt, and Ca. Absence rates and presenteeism levels (range 0–10=worst score) were measured using the Work Productivity and Activity Impairment (WPAI) questionnaire. Other job related questions were about demands and satisfaction, help from colleagues and opportunities to postpone or organise ones work. Disease related variables included HAQ, EQ-5D, VAS health status. The Hospital Anxiety and Depression Scale (HADS) was also completed. Cross-sectional univariable and multivariable Zinb regression models were applied to assess the association between these disease related, psychological, and work related factors and presenteeism, adjusting for age, gender and country. Due to high co-linearity only HAQ and HAD-anxiety were included in the multivariable model. Results A total of 544 patients (AS=138, OA=43, PsA=97, RA=266) were recruited with a mean (SD) age of 4710 yrs and a median symptom duration [IQR] of 105–18 yrs; 62% were women. 17% had a manual occupation. 111/544 (20.4%) reported being absent during the previous 7 days. Mean (SD) presenteeism score was 2.9 (2.7). In univariable analyses, worse self-reported disease activity and high levels of depression and anxiety were significantly associated with presenteeism in both the count and inflate part of the model (table 1). Less consistent results were observed for work related factors. In the multivariable model (s, 95% CI), worse functional disability was associated with presenteeism in both the count and excess zero part of the model (0.63; 0.49, 0.78: −2.70,–3.73, −1.66, resp). In addition, higher HAD-anxiety score (−0.09; −0.18; −0.00) was associated with a decreased likelihood of excessive zeros whilst not receiving help from colleagues (1.47; 0.64, 2.30) was associated with an increased likelihood of excessive zeros. There was a trend towards an association between very demanding jobs (−0.79; −1.63, 0.05) and presenteeism. VAS=visual analogue scale (0–100 worst score); EQ-5D=EuroQol-5D (−0.11–1=perfect health); HAD=Hospital Anxiety Scale (0–21=abnormal); PASS=do you feel your current condition is satisfactory, when you take your general functioning and your current pain into account (satisfactory/unsatisfactory). Count part=score in those with a score >0; inflate part=estimate of excess zero scores. Conclusions In this large international study of patients with IA and OA having a median symptom duration of 10 years, worse functional ability was the main factor associated with presenteeism. Disclosure of Interest None declared

Background Digital ulcers (DUs) affect about half of systemic sclerosis (SSc) patients during disease course. In some patients, peripheral vasculopathy can promote critical ischemia and gangrene, severe complications with potential life threatening consequences. Recently the DUO registry suggested a 18% prevalence of gangrene in DU-SSc patients, with smoking and a high number of DUs being predictive factors. However, little is known about gangrene in unselected SSc patients. Objectives To investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods We included patients from the EUSTAR database satisfying the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. We extracted from this database data regarding the reporting of DUs, DUs history and digital gangrene. Centres were asked for supplementary data on traditional cardiovascular (CV) risk factors. We analysed by uni- and multivariable logistic regression the cross-sectional relationship between gangrene and its potential risk factors such as history of DUs, cutaneous subset, disease duration, autoantibodies, traditional CV risk factors. Furthermore, longitudinal data were analysed by Cox proportional hazards regression. Results 1757 patients matched the inclusion criteria (age at inclusion 55.9±14.5 years, disease duration since first non-Raynaud’s symptom 7.9±10.3 years and from onset of Raynaud’s phenomenon (RP) 11.1±11.0 years, male sex 16.7%, 24.6% diffuse cutaneous subset (DcSSc)). At inclusion, 8.9% of patients had either current or previous digital gangrene, 15.7% had current DUs and a further 25.8% had previously had DUs. Among the potential risk factors, older age, a history of DUs and the DcSSc subset were statistically significant risk factors in the cross-sectional multivariable model. For the longitudinal part, during the entire follow-up (median [Q1,Q3] 13.1 [9.6, 19.3] months), 16/771 patients had incident gangrene (2.1%), accounting for an incidence of 1.73/100 patient-years. All 16 patients who developed incident gangrene had previously had DUs and gangrene. Further risk factors for incident gangrene were the DcSSc subset and longer disease duration: hazard ratio [95% confidence interval]: 8.97 [2.90–27.71] and 1.08 [1.04–1.13] respectively, both p Conclusions In unselected SSc patients, gangrene still occurs in about 9% of SSc patients. Of the most importance, a history of DUs and, to a lesser extent, the DcSSc subset are strongly and independently associated with gangrene, while traditional CV risk factors were not identified as risk factors. Our results confirm that gangrene is still a concern in SSc. They emphasise the importance of microvascular SSc-associated disease in the pathogenesis of gangrene and suggest that the DcSSc subset should be prioritised for risk-stratification of the patients. Acknowledgements The authors thank all the contributing EUSTAR investigators and patients. Disclosure of Interest C. Mihai Grant/research support from: Actelion Pharmaceuticals Ltd, Abbvie, Speakers bureau: Roche, Geneva Romfarm, O. Distler Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Roche, Consultant for: Actelion, Bayer, BiogenIdec, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Sinoxa, A. M. Gheorghiu Grant/research support from: Geneva Romfarm, Abbvie, P. Constantin: None declared, R. Dobrota Grant/research support from: Actelion Pharmaceuticals Ltd, Pfizer, S. Jordan: None declared, V. Smith Grant/research support from: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH, Bayer AG, Roche NV/SA, Fund for Scientific Research Flanders, E. Hachulla: None declared, J. Henes: None declared, E. Siegert: None declared, S. Vettori: None declared, U. Muller-Ladner: None declared, M. Matucci-Cerinic: None declared, Y. Allanore Grant/research support from: BMS, Genentech-Roche, Inventiva, Pfizer, Sanofi, Consultant for: Actelion, Bayer, Biogen, Genentech-Roche, Galapagos, Medac, Pfizer, Sanofi, Servier, UCB

Background Skin involvement is a main domain in the assessment of patients with systemic sclerosis (SSc), and the modified Rodnan skin score (mRSS) is a primary outcome measurement in SSc clinical trials. Recent studies on large SSc cohorts have shown that lowering the upper threshold of mRSS as a study inclusion criterion leads to cohort enrichment with patients with progressive skin disease. Limitations of these studies were lack of racial diversity and low proportion of patients with anti-RNA-Polymerase III (Pol3) antibodies. Objectives As the Texas-based GENISOS is an ethnically diverse cohort and includes a large proportion of Pol3-positive patients, this study aimed to assess the effect of different mRSS cut-off values at baseline on progression of skin fibrosis after one year of follow-up. Methods We extracted data from GENISOS for patients fulfilling the 1980 ACR criteria for SSc and the Le Roy criteria for diffuse cutaneous SSc, who had a mRSS ≥7 at inclusion and a follow-up visit with documented mRSS at 12±2 months. Progressors were defined as having an increase in mRSS >5 points and ≥25% from the baseline to 2nd visit, while regressors were defined as having a decrease in mRSS of >5 points and ≥25%. To identify the optimal cut-off of baseline mRSS that yields the highest sensitivity for progressive skin fibrosis, we developed ROC curves and logistic regression models with “progression” as outcome variable and a binary variable of baseline mRSS cut-off point as predictor. Results We identified 152 patients (age and disease duration [median, Q1-Q3, years] 49.5, 40.2–57.3 and 2.2, 1.1–3.3 respectively, 22.4% males) who matched the inclusion criteria. The proportion of patients of African American ethnicity was 31/152 and 50/152 were Pol3-positive patients, both substantially higher than in European cohorts. After one year, 17 patients (11.2%) classified as progressors and 51 (33.6%) as regressors. Progressors were more frequently positive for anti-topoisomerase antibodies (37.5% vs. 15.3%, p=0.028), negative for anti-Pol3 antibodies (93.8% vs. 62.3%, p Sixteen of 17 progressors, but only 33 of 51 regressors had a baseline mRSS ≤27. The mRSS cut-off of ≤27 had the highest probability of progression (odds ratio 9.1, 95% confidence interval 1.2–70.9, p Conclusions This analysis reconfirmed, in a population rich in patients of African American origin and with high prevalence of Pol3 antibodies, that setting a lower upper threshold of mRSS at study inclusion increases the proportion of progressors and reduces the absolute number of regressors. This confirms that this recruitment strategy should be used for clinical trial design in early diffuse SSc. Acknowledgements The authors wish to thank all GENISOS investigators and patients. Disclosure of Interest C. Mihai Grant/research support from: Actelion Pharmaceuticals Ltd, Abbvie, Speakers bureau: Roche, Geneva Romfarm, R. Dobrota Grant/research support from: Actelion Pharmaceuticals Ltd, Pfizer, S. Assassi Grant/research support from: U.S. National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases, U.S. DOD Peer Reviewed Medical Research Program, Consultant for: Boehringer-Ingelheim, M. Mayes Grant/research support from: U.S. National Institutes of Health-National Institute of Arthritis and Musculoskeletal and Skin Diseases, U.S. DOD Peer Reviewed Medical Research Program, Consultant for: Boehringer-Ingelheim, Genentech, Astellas, Mitsubishi-Tanabe, O. Distler Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Roche, Consultant for: Actelion, Bayer, BiogenIdec, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Sinoxa, UCB

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 In rheumatoid arthritis (RA) the “window of opportunity” has a crucial role for better long-term outcomes.1 The ACR/EULAR remission criteria for RA are mostly represented by clinical parameters, while ultrasound (US) is not included.2 However, in early diagnosed and early treated patients, who fulfil the remission criteria, residual US modifications can be identified.3 Objectives The aim of this study was to investigate whether significant US-detectable differences between early RA (ERA) patients treated for one year and healthy controls (HC) are present. Methods We enrolled in this cross-sectional study consecutive patients with ERA at 1 year after having initiated RA disease-modifying (DMARD) therapy and who had received treatment following RA recommendations. Only patients who had fulfilled EULAR/ACR 2010 criteria for RA4 and with symptoms duration of less than 1 year at treatment initiation were included. US exams were performed in 10 joints bilaterally (wrist, MCP II-V) by using both gray-scale and Doppler for evaluating synovitis was graded according to a semi-quantitative 4-point scale (0–3). A total US score for synovitis was calculated by adding the values recorded at each joint site. The presence of erosions was also recorded. Finally, US results obtained in patients were compared to those detected in HC. Results 84 subjects were enrolled – 45 ERA patients and 39 HC. In ERA patients the mean duration of symptoms prior to diagnosis was 3.5±3.5 months. The demographic, clinical and US data are reported in table 1. Conclusions Patients with RA, who had been early diagnosed and early treated, after 1 year of tight control had still US inflammatory and erosive changes compared to HC. US assessment gives an added value to clinical evaluation in ERA, for its capacity to detect residual inflammatory abnormalities, even under optimised treatment and consequent structural lesions. References [1] van Nies JAB, et al. Ann Rheum Dis2015;74:806–812. [2] Bykerk VP1, Massarotti EM. Rheumatology2012;51(Suppl 6):vi16–20. [3] Vergara F, et al. Reumatol Clin2017Mar 18. [4] Aletaha D, et al. Arhritis Rheum2010;62:2569–2581. Disclosure of Interest None declared

Background 20%–40% of the patients are declared nonresponders to at least one of the biologic agents. Objectives to test the possible predictive role of RF type IgM and IgA, anti-CCP, anti-MCV,14–3–3eta protein and COMP on a group of patients treated with anti-TNFα agents. We also followed the evolution of serum titres of these biomarkers under biologic therapy and the impact of smoking regarding response to treatment. Methods prospective and observational study including 64 patients followed 12 months with active RA, uncontrolled by csDMARDs. Clinical assessment was performed at 0,6 and 12 months according to ACR criteria and evaluation of treatment response according to EULAR criteria (good/moderate/nonresponder). Results Following baseline immunological parameters titres and the response at 6 months, tests for identifying differences between the groups showed that lower titres of both RF isotypes, anti-CCP,14–3–3eta protein and COMP had predictive value on achieving a good EULAR response at 6 months. Grouping patients in 2 categories (responders/nonresponders), just 14–3–3eta protein and anti-CCP maintained their predictive value for the response at 6 months. For the visit at 12 months, lower baseline titres for RF type IgM (92.93±120.22 U/ml,p=0.010) and IgA (49.96±98.08 U/ml,p=0.002) had predictive value for achieving a good response at 12 months. We didn’t obtain other informations grouping patients in 2 categories. The status pretreatment influenced the good response for COMP at 6 months (p=0.001) and RF IgA at 12 months (p=0.004). Using multivariate logistic regression methods we obtained a statistical model for predicting the response at 6 months including normal values for 14–3–3eta protein, anti-CCP and COMP (Hosmer and Lemeshow according test λ²=5.795, p=0.670≥0.05 with a predictive response accuracy of 89.1%). Smoking had a negative impact on the EULAR response as well as on 2 groups respose at 6 months of treatment (p=0.017). Following the evolution of serum levels, we noticed a reduction for all biomarkers tested, statistically significant at 6 and/or 12 months from baseline. Conclusions in the future a version using multiple biomarkers could increase accuracy for identifying pretreatment patients who will respond to anti-TNF therapy. Smoking has a negative impact on the response to biologic treatment. Disclosure of Interest None declared