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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.

BackgroundThe gastrointestinal (GI) tract is frequently affected in systemic sclerosis (SSc), leading to considerable morbidity and even mortality. While important progress has been made in the last years regarding treatment of SSc, there is no disease-modifying treatment available for SSc-related GI involvement.ObjectivesWe aimed to identify, in an observational cohort study of real-life patients with SSc, an association between immunosuppressive therapy and the severity of GI symptoms, measured by the University of California at Los Angeles / Scleroderma Clinical Trial Consortium Gastro-Intestinal Tract instrument 2.0 (UCLA GIT 2.0).MethodsWe selected patients from our EUSTAR centre who met the 2013 ACR/EULAR classification criteria for SSc and had at least two visits with completed UCLA GIT 2.0 questionnaires, with an interval of 12±3 months between visits. We defined the first visit with a completed UCLA GIT 2.0 questionnaire as baseline visit. Immunosuppressive therapy was defined as exposure for at least 6 months between the two visits to at least one of the following drugs, regardless of indication: mycophenolate mofetil (MMF), cyclophosphamide, methotrexate, azathioprine, leflunomide, glucocorticoids (>10mg/d prednisone-equivalent), rituximab, tocilizumab, and abatacept. The study outcome was the UCLA GIT 2.0 score at the follow-up visit. We performed multivariable linear regression with this outcome as dependent variable and immunosuppressive therapy during follow-up, immunosuppressive therapy before baseline, baseline UCLA GIT 2.0 score and several baseline parameters selected by clinical judgment as potentially influencing GI symptoms, as independent variables. Multiple imputation was implemented to handle missing values.ResultsWe included 209 patients. Baseline characteristics were: 82.3% female, median (IQR) age 59.0 (48.6, 68.2) years, median disease duration 6.0 (2.7, 12.5) years, 40 (19.1%) diffuse cutaneous SSc, median baseline UCLA GIT 2.0 score 0.19 (0.06, 0.43). Of these, 71 patients were exposed to immunosuppressive therapy during the observation period: 27/71 methotrexate, 1/71 cyclophosphamide, 17/71 MMF, 3/71 leflunomide, 3/71 azathioprine, 6/71 glucocorticoids >10mg/d, 16/34 rituximab, 18/34 tocilizumab. Patients on immunosuppressive therapy during the observation period had, compared to patients without such treatment, overall more severe SSc, higher prevalence of treatment with proton pump inhibitors, similar UCLA GIT 2.0 scores at baseline and at follow up and tendentially less severe GI symptoms at baseline and follow-up by medical history. In multivariable linear regression, immunosuppressive therapy, lower body mass index, longer disease duration and lower baseline UCLA GIT 2.0 score were significantly associated with lower (better) UCLA GIT 2.0 scores at follow-up (Table 1).Table 1.Predictors of UCLA GIT 2.0 score at follow-upEstimates95% CIpAge0.002-0.001 – 0.0060.136Sex [male]-0.056-0.172 – 0.0610.347Disease duration-0.005-0.009 – -0.0000.030Body mass index0.0140.002 – 0.0250.017UCLA GIT 2.0 total score baseline0.6900.571 – 0.809Immunosuppressive therapy during observation period-0.119-0.228 – -0.0100.032Immunosuppressive therapy before baseline0.080-0.032 – 0.1920.160Modified Rodnan Skin Score-0.001-0.008 – 0.0070.860Forced vital capacity-0.001-0.004 – 0.0010.302Erythrocyte sedimentation rate0.003-0.001 – 0.0060.116Proton pump inhibitors-0.034-0.120 – 0.0520.435(Intercept)-0.120-0.531 – 0.2910.566Baseline factors associated with the total UCLA GIT 2.0 score at the end of the observation period. Multiple linear regression model with imputation for missing variables. N=209 patientsConclusionImmunosuppressive treatment was associated with lower UCLA GIT 2.0 scores, which suggests potential effects of immunosuppressants on GI manifestations in patients with SSc. These results need verification in additional studies and randomised controlled clinical trials.References[1]Khanna D et al. Arthritis Rheum, 2009; 61: 1257-63.Disclosure of InterestsLea Stamm: None declared, Alexandru Garaiman: None declared, Norina Zampatti: None declared, Mike O. Becker Speakers bureau: Mepha, MSD, Novartis, GSK, Bayer and Vifor, Consultant of: Mepha, MSD, Novartis, GSK, Bayer and Vifor, Grant/research support from: Mepha, MSD, Novartis, GSK, Bayer and Vifor, Cosimo Bruni Speakers bureau: Actelion, Eli-Lilly, Boehringer-Ingelheim, Grant/research support from: Abbvie, EUSTAR, Gruppo Italiano Lotta alla Sclerodermia (GILS), SCTC, Rucsandra Dobrota Consultant of: Boehringer-Ingelheim, Grant/research support from: Iten-Kohaut Foundation, Muriel Elhai: None declared, Sherif Ismail Grant/research support from: EULAR scientific training grant for young fellows 2021, Suzana Jordan: None declared, Aurora Tatu: None declared, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim, Carina Mihai Speakers bureau: Boehringer-Ingelheim, Mepha, MED Talks Switzerland, Consultant of: Boehringer-Ingelheim, Janssen, Grant/research support from: Boehringer-Ingelheim, Janssen, Roche.

BackgroundUpper-gastrointestinal involvement (GI) is associated with more severe interstitial lung disease in patients with systemic sclerosis (SSc-ILD). However, there are many unexplored GI risk factors for the presence of SSc-ILD which could be potentially revealed by machine learning algorithms.ObjectivesThe aim of our study was to identify GI related risk factors for the presence of SSc-ILD using machine learning algorithms based on decision trees (DT).MethodsData of the last follow-up visit from consecutive patients fulfilling the 2013 ACR/EULAR SSc classification criteria recorded in our local EUSTAR registry were used for this study.The study outcome was the presence of SSc-ILD on high-resolution computed tomography.Two sets of predictors were identified based on their potential association with GI. The first set contains the following variables available in the EUSTAR registry: esophageal symptoms (dysphagia and reflux), stomach symptoms (early satiety, vomiting), intestinal symptoms (diarrhea, bloating and constipation), malabsorption syndrome, body-mass-index (BMI) and proton pump inhibitor therapy, calcium channel blocker therapy and immunosuppressive therapy. In the second set, we replaced the first three EUSTAR variables of the first set with the scales of the UCLA Gastrointestinal Tract Questionnaire 2.0 (UCLA-GIT).Of these two sets, the most important variable was selected using three different DT-based algorithms: (1) recursive partitioning and regression trees (RPART) –which uses trees to build decision rules, (2) random forest (RF) - an ensemble of DT built in parallel, and (3) gradient boosting machines (GBM) - an ensemble of DT built sequentially. The selected variables were eventually integrated with established predictors for presence of SSc-ILD (diffuse cutaneous subset, anti-Scl-70 positivity, male gender, forced vital capacity [FVC] and diffusion capacity of the lung for carbon monoxide-single breath [DLCO-SB]) into final prediction models for SSc-ILD presence using RPART, RF and GBM respectively. Their performance was evaluated by C-statistics. The importance of the newly detected predictor was assessed by variable importance plots (VIPs).ResultsWe included in our study 334 patients. The median age was 61 [IQR: 50-69] years, 59 (17.7%) were males and 266 (79.6%) had limited cutaneous SSc. Median BMI was 23 [IQR: 21-26] kg/m2, 133 (39.8%) of the patients had SSc-ILD, median FVC% 93 [IQR: 81-105], DLCO 72.5 [56-84] and. Of the UCLA-GIT scales the highest score was for the distension/bloating with a value of 0.50 [IQR: 0-1.24]. Regarding medications, 167 (50%) patients were exposed to PPI, 39 (11.7%) to CCB and 105 (31.4%) to immunosuppressive therapy.The BMI was deemed by all three algorithms as the most important predictor of SSc-ILD among both sets of GI related variables (Figure 1A-F). The final model, which included established risk factors for presence of ILD and the BMI, supported the importance of BMI in predicting the SSc-ILD. The VIPs obtained by GBM also ranked the BMI as the most important predictor.Figure 1.Tree-based algorithms revealing the importance of BMI for prediction of SSc-ILD. Panels A, B and C are variable importance plots (VIPs), which reveals the most important GI-predictor for occurrence of SSc-ILD in the EUSTAR set– the predictor with the highest relative importance is the most important predictor. Panels D, E and F are VIPs reveals the most important GI-predictor for occurrence of SSc-ILD in the UCLA-GIT set.A lower BMI was associated with presence of SSc-ILD (C-statistics for the RPART, RF and GBM models were 0.79, 0.70 and 0.76, respectively, corresponding to a fair accuracy). As expected, also a lower FVC, and DLCO-SB, and a positivity for Scl-70 ab were associated with presence of ILD.ConclusionLower BMI is a novel promising predictor for the presence of ILD, which should be confirmed in additional analyses.Disclosure of InterestsAlexandru Garaiman: None declared, Carina Mihai Speakers bureau: MEDtalks Switzerland, Mepha, Rucsandra Dobrota Consultant of: Actelion and Boehringer-Ingelheim, Grant/research support from: Articulum Fellowship, Pfizer, Actelion, Cosimo Bruni Speakers bureau: Eli-Lilly, Actelion, Boehringer-Ingelheim, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European,, Scleroderma Trials and Research Group (EUSTAR), Scleroderma Clinical Trials Consortium (SCTC), AbbVie, Muriel Elhai: None declared, Suzana Jordan: None declared, Lea Stamm: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Roche, Merck Sharp & Dohme, ARXX Therapeutics, Lilly and Medscape, Consultant of: Actelion, Boehringer Ingelheim, Jansen, Roche, Merck Sharp & Dohme, ARXX Therapeutics, Lilly and Medscape, Grant/research support from: Boehringer Ingelheim, Bayer, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche, Pfizer, Roche, Sanofi, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon, Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Prometheus Biosences, Roche, Roivant, Topadur and UBC, Lilly, Pfizer, Grant/research support from: Kymera, Mitsubishi Tanabe, Mike O. Becker Speakers bureau: Mepha, MSD, Novartis, GSK, Bayer and Vifor

BackgroundInterstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc). European consensus guidelines consider that some patients with mild disease might not need pharmacological treatment (1). Up to now, the disease characteristics and the disease course of non-treated SSc-ILD patients remain unknown.ObjectivesTo describe disease characteristics and the disease course of non-treated SSc patients with ILD.MethodsWe included patients from our local EUSTAR center registered since 2008, who had a diagnosis of ILD on high-resolution computed tomography (HRCT) and available data on pulmonary function tests and treatment. Longitudinal study included patients with at least one follow-up visit. Patients were classified as treated if they received a potential ILD modifying drug (immunosuppressive therapy or nintedanib). Treated and untreated patients were compared at baseline. Progression in the untreated group was defined as (i) forced vital capacity (FVC) decline from baseline of ≥10% or (ii) an FVC decline of 5-9% in association with a decline in diffusing capacity for carbon monoxide (DLCO) of ≥15%, or (iii) start of a ILD modifying treatment during follow-up. In the untreated group, patients who progressed at any time were compared with patients with stable disease during follow-up. Multivariable logistic regression was performed to identify (i) factors associated with non-prescription of a treatment in ILD patients at baseline and (ii) factors associated with progression in the untreated patients. Covariates were selected according to clinical experience and literature evidence.ResultsAmong 496 patients included in our cohort, 209 (42%) patients had ILD on baseline HRCT: 48/209 (23%) were males, median disease duration 8 [IQR: 4-12] years, 67/209 (32%) of diffuse cutaneous subset and 86/209 (41%) had anti-Scl70 antibodies.Among them, 142/209 (68%) did not receive any potentially ILD modifying treatments at baseline. Untreated patients were older (59 vs. 54 years), had a longer disease duration, were less frequently smokers, had more frequently anticentromere antibodies and lower levels of CRP. They had more frequently a limited extent (In multivariable logistic regression, older age (OR: 1.04 [1.01-1.08], p=0.021), a less extensive disease on HRCT (OR: 0.29 [0.09-0.90], p=0.037) and less frequent prescription of glucocorticoids (OR: 0.036 [0.12-0.92], p=0.037) were independently associated with absence of ILD modifying treatment prescription in our cohort.From the 142 untreated patients, 96 were followed-up for 64 [39-96] months. Of these, 56 (58%) patients showed progression of ILD, of whom 43 progressed by lung function parameters. Of these 56 patients, 31 (56%) progressed in the first 18 months. Diffuse cutaneous subtype (OR: 5.26 [1.26-27.62], p=0.031), shorter disease duration (OR: 0.95 [0.90-0.99], p=0.035) and oesophageal symptoms (reflux, dysphagia) (OR: 3.51 [1.12-12.18], p=0.036) at baseline were independent predictors of progression during follow-up in untreated patients.ConclusionA considerable number of SSc patients with ILD are not treated in clinical practice, in particular patients with limited cutaneous SSc, older age and an overall less extensive ILD. However, during a follow-up of 5 years, contrary to the common belief, about 60% of the untreated patients showed ILD-progression. The diffuse cutaneous subtype, shorter disease duration and oesophageal symptoms at baseline characterized these patients. With the development of effective and safe therapies for SSc-ILD, our results support a change in practice for selecting patients for treatment.References[1]Hoffmann-Vold A-M, et al. The Lancet Rheumatology. 2020;2(2):e71-e83.Disclosure of InterestsMoritz Scheidegger: None declared, Alexandru Garaiman: None declared, Carina Mihai Speakers bureau: Boehringer-Ingelheim, MED Talks Switzerland, Consultant of: Boehringer-Ingelheim (advisory board), Janssen (advisory board), Mike O. Becker Speakers bureau: Mepha, MSD, Novartis, GSK, Bayer and Vifor, Consultant of: Mepha, MSD, Novartis, GSK, Bayer and Vifor (advisory board fees), Rucsandra Dobrota Consultant of: Boehringer-Ingelheim (Advisory Board), Cosimo Bruni Speakers bureau: Eli-Lilly2018-2021, Actelion2019, Boehringer-Ingelheim2020-2021, Grant/research support from: AbbVie (educational grant 2021), Suzana Jordan: None declared, Håvard Fretheim Speakers bureau: Personal fees form Bayer and non-financial support from GSK and Actelion, outside the submitted work., Øyvind Midtvedt: None declared, Hilde Jenssen Bjørkekjær: None declared, Imon Barua: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Janssen, Medscape, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim, Muriel Elhai Speakers bureau: Speaker fees: BMS outside the submitted work

BackgroundAn accurate assessment of nailfold capillaroscopy (NFC) images has great importance in the diagnosis and prognosis of systemic sclerosis (SSc). To overcome some of the inherent problems with NFC image analysis (operator/observer bias, time requirements), there is an interest to automate and standardize NFC image assessment using computer vision algorithms, such as the Vision Transformer (ViT), which are based on recent advances in deep learning.ObjectivesOur aims were (1) to implement and assess the performance and the reliability of ViT in detecting changes on NFC images, and (2) to compare the performance of ViT to that of practicing rheumatologists.MethodsFor this study, we used NFC images of patients with SSc enrolled in our European Scleroderma Trials and Research group (EUSTAR) and Very Early Diagnosis of Systemic Sclerosis (VEDOSS) local registries. Concretely, we included routine NFC images (all NFC images available – digit II to V of both hands-, irrespective of any image artefacts) of patients aged ≥ 18 years with visits between 2012 and 2021, who fulfilled either the 2013 American College of Rheumatology / European League Against Rheumatism classification criteria for SSc (established disease) or the preliminary criteria for VEDOSS (mild/early disease).ViT was trained to identify the following NFC signs of microangiopathy: enlarged capillaries (apex diameter of the capillary > 20 µm, and < 50µm), giant capillaries (> 50 µm), loss of capillaries (< 7 capillaries/mm), and microhaemorrhages. Absence of any of these signs was considered as being a “normal NFC”, while presence of any of these signs was seen as an abnormal NFC image. Its performance was evaluated in a cross-fold (k = 5) validation setting, and the gold standard was the treating physician. Area under the ROC curve (AUC) was used as indicator of the performance. Considered cut-offs for AUC were 90-100% - excellent, 80-89.9% - good, 70-79.9% - fair, 60-69.9% - poor, 50-59.9% - fail. From the first cross-fold, a randomly sampled reliability set was created which was used to compare the NFC assessment performance of four rheumatologists (three invited and trained annotators and the treating physician) with that of of ViT.ResultsWe analysed 17,126 NFC images of 234 EUSTAR patients (14.6% males, 67.8% limited cutaneous SSc, median age 57 years, median disease duration 9 years) and 55 VEDOSS patients (92.7% females, median age 44 years, median time elapsed since first Raynaud’s phenomenon 5 years). ViT had fair to excellent performance in identifying the different NFC changes across all five folds (of 3443 NFC images each), with an area under the ROC curve ranging from 78.59% to 90.4% (Figure 1a).Figure 1.Performance of the ViT: (a) AUCs values for ViT in diagnosing the respective feature on NFC image. (b) Sensitivity / specificity trade-off across the images in the reliability set. The blue lines show the ROC curves corresponding to the ViT predictions, with ViT’s AUC, “optimal” sensitivity and specificity shown in the box. Also shown are the point performances of each of the four annotators, with performances below the blue line indicating lower performance than ViT.In the reliability set (see Figure 1b), we observed highest performance for diagnosing giant capillaries (AUC =92.89%) followed by identification of enlarged capillaries (AUC = 91.7%). Good AUCs were seen in depicting capillary loss (AUC = 87.3%), microhemorrhages (AUC = 85.9%) and the abnormal/normal NFC classification (AUC = 84.7%). The rheumatologists had generally higher performance in assessing NFC images. However, ViT outperformed two rheumatologists with different experience in classifying capillary loss and enlarged capillaries, respectively.ConclusionViT is a modern, well performing and readily available AI model to assess signs of microangiopathy on NFC images acquired during routine practice.Disclosure of InterestsAlexandru Garaiman: None declared, Farhad Nooralahzadeh: None declared, Carina Mihai Speakers bureau: MEDtalks Switzerland, Mepha, Nikitas Gkikopoulos: None declared, Nicolas Perez Gonzalez: None declared, Mike O. Becker Speakers bureau: Mepha, MSD, Novartis, GSK, Bayer and Vifor, Oliver Distler Speakers bureau: Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche, Pfizer, Roche, Sanofi, Consultant of: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon, Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Prometheus Biosences, Roche, Roivant, Topadur and UBC, Lilly, Pfizer, Grant/research support from: Kymera, Mitsubishi Tanabe, Michael Krauthammer Speakers bureau: Oncobit, Britta Maurer Speakers bureau: Boehringer-Ingelheim, Medtalk, Pfizer, Roche, Actelion, Mepha, and MSD, Consultant of: Novartis, Boehringer Ingelheim, Janssen-Cilag, Grant/research support from: AbbVie, Protagen, Novartis Biomedical Research

OBJECTIVES To evaluate the feasibility, validity, reliability, and responsiveness of the Hospital Anxiety and Depression Scale (HADS) and to analyse its model structure in patients with systemic sclerosis (SSc). METHODS In this study, 316 SSc patients were included; of these, 159 participated in the responsiveness analysis. Psychometric properties were tested in analogy to the Outcome Measures in Rheumatology (OMERACT) filter and an exploratory and confirmatory factor analysis was performed to examine the structure of HADS. RESULTS The HADS showed adequate feasibility, validity, reliability, and responsiveness to clinically relevant worsening of the disease. For our population of SSc patients, the HADS model with two sub-scales, HADS-A and HADS-D, and a general scale HADS-S, measuring anxiety, depression, and distress, respectively, was most appropriate. The rates of anxiety, depression, mixed anxiety-depressive disorder (MADD) and distress identified by HADS were 32.2%, 25.9%, 18.5%, and 49.5%, respectively, in our cohort. CONCLUSIONS The psychometric properties of the HADS make it useful for screening in SSc, where anxiety, depression, MADD, and distress represent a significant burden to patients.

Background:As a rare, complex, and heterogeneous disease, mixed connective tissue disease (MCTD) represents a challenge for clinical practice.Objectives:We aimed to unravel potential pitfalls including correct referral diagnosis, fulfilment of diagnostic criteria, distinction from other CTDs, disease course and activity, and treatment modalities.Methods:We analysed the prospectively collected MCTD cohort at our tertiary referral centre. The patients’ medical histories were investigated for fulfilment of Sharp’s (1), Kasukawa’s (2), and Alarcón-Segovia’s (3) diagnostic MCTD criteria. We defined overlap syndromes as simultaneous fulfilment of clinical as well as immunological criteria of two defined rheumatic diseases. Disease conversion was defined as emergence of new symptoms and autoantibodies consistent with another rheumatic disease. Remission was defined by simultaneous systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trial and research (EUSTAR) activity index Results:Out of 85 patients initially referred as MCTD, only one third fulfilled the diagnostic MCTD criteria. Most of the remaining patients had undifferentiated CTD (29%) or overlap syndromes (20%). In our final cohort of 33 MCTD patients, 6 (48%) also met the classification criteria of systemic sclerosis, 13 (39%) those of systemic lupus erythematosus (SLE), 6 (18%) those of rheumatoid arthritis, and 3 (9%) those of primary myositis. Over the median observation period of 4.6 (1.6, 9.9) years, only two patients (6%) underwent disease conversion from MCTD to SLE and no patient converted towards other diseases. The number of patients in remission increased from 6 (18%) to 15 (45%) due to introduction of immune modulatory treatment. Combination therapy was favoured in most cases (17 patients, 52%), whereas monotherapy was less frequent (12 patients, 36%), and only 4 (12%) patients remained without immune modulators until the end of the follow-up period. Hydroxychloroquine, prednisone, and methotrexate were the most frequently used medications in our cohort.Conclusion:Our study showed a high risk for misdiagnosis for patients with MCTD. Phenotype conversion was a very rare event. As a multi-organ disease, MCTD required prolonged (combined) immunosuppressive therapy to achieve remission. The establishment of an international registry with longitudinal data from observational multi-centre cohorts might represent a first step to address the many unmet needs of MCTD.References:[1]Sharp GC. Diagnostic criteria for classification of MCTD. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 23-30.[2]Kasukawa R, Tojo T, Miyawaki S, Yoshida H, Tanimoto K, Nobunaga M, et al. Preliminary diagnostic criteria for classification of mixed connective tissue disease. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 41-7.[3]Alarcón-Segovia D, Villarreal M. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 33-40.Disclosure of Interests:Adrian Wanzenried: None declared, Alexandru Garaiman: None declared, Suzana Jordan: None declared, Oliver Distler Consultant of: O.D. had consultancy relationship and/or has received research funding from Abbvie, Actelion, Acceleron Pharma, Amgen, AnaMar, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, Catenion, Competitive Drug Development International Ltd, CSL Behring, ChemomAb, Curzion Pharmaceuticals, Ergonex, Ga-lapagos NV, Glenmark Pharmaceuticals, GSK, Inventiva, Italfarmaco, iQone, iQvia, Lilly, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Target Bio Science and UCB in the area of potential treatments of scleroderma and its complications., Britta Maurer Consultant of: Boehringer-Ingelheim, Grant/research support from: AbbVie, Protagen, and Novartis Biomedical Research as well as congress support from Pfizer, Roche, Actelion, mepha, and MSD.

Background:Digital ulcers (DUs) affect half of the patients with systemic sclerosis (SSc) and can be complicated by gangrene and amputation. The direct involvement of platelets in the development of DUs has been suggested by in vitro studies, which encouraged physicians to consider platelet inhibitors as a therapeutic option in the management of DUs. However, until now, there is no clinical study to assess the efficacy of platelet inhibitors for DUs in SSc patients.Objectives:To demonstrate a possible relationship between treatment with platelet inhibitors and the occurrence of DUs at the next follow-up visit in patients with SSc.Methods:This study used prospectively collected data from the European Scleroderma Trials and Research group (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR SSc classification criteria with complete longitudinal data on the presence of DUs and platelet inhibitors were included in the analysis. Multiple imputation using a random forest algorithm was implemented to handle missing values.The dataset was split into a derivation and validation cohort. To investigate the response for the binary dependent variable of DUs, a generalized linear mixed model (GLMM) was developed in the derivation cohort and validated using ROC analysis and Brier scores to address discrimination and calibration, respectively.Results:Of 3,463 patients (2,961 in the derivation cohort, 722 in the validation cohort), 453 had current DUs at the baseline and 245 were exposed to platelet inhibitors (table 1).Our GLMM revealed that the exposure to platelet inhibitors is associated with a reduced risk of DUs at the next follow up visit (OR = 0.33, 95% CI = [0.13 to 0.82]). Further factors associated with absence or presence of DUs at the next follow-up visit are shown in figure 1. This confirmed the previously identified risk factors for the presence of DUs, supporting the overall robustness and the validity of our model.The performance was evaluated by ROC curve analysis and showed an AUC = 97.97% (95% CI = [96.93% to 97.67%]) for the derivation cohort and AUC = 77.3% (95% CI = [74.01% to 81.39%]) for the validation cohort, respectively, showing an acceptable discrimination. The Brier score was 0.05 in the derivation cohort and 0.07 in the validation cohort, suggesting a good calibration of the model.Conclusion:Our model, with acceptable discrimination and good calibration, suggests a positive treatment effect of platelet inhibitors on DUs in clinical practice.Table 1.Baseline characteristics of patients before imputationCharacteristicsOverallDerivation setValidation setn3,4632,691772Age (median [IQR])56.00 [47.00, 66.00]56.00 [47.00, 65.00] 57.00 [48.00, 67.00]Disease duration (median [IQR]) 9.00 [4.00, 16.00] 9.00 [4.00, 16.00] 8.00 [4.00, 15.00]Disease subset = Limited cutaneous SSc (%) 1562 (65.2) 1164 (64.6) 398 (66.9)DUs (%): Current 453 (13.1) 378 (14.0) 75 (9.7)DUs (%): Never 1783 (51.5) 1326 (49.3) 457 (59.2)DUs (%): Previously 1227 (35.4) 987 (36.7) 240 (31.1)mRSS (median [IQR]) 5.00 [2.00, 11.00] 6.00 [2.00, 12.00] 4.00 [1.00, 11.00]Joint Contractures = Yes (%) 881 (26.8) 770 (29.4) 111 (16.5)LVEF (median [IQR])62.00 [60.00, 65.00]60.00 [60.00, 65.00] 65.00 [60.00, 67.00]Dyspnea NYHA III and IV (%)300 (9.5)214 (8.6)86 (12.7)Pulmonary hypertension = Yes (%) 244 (10.7) 200 (11.3) 44 (8.4)Lung fibrosis on HRCT = Yes (%) 685 (46.6) 600 (47.7) 85 (39.7)FVC % predicted (median [IQR])97.00 [82.00, 111.00]95.00 [81.00, 110.00]101.00 [85.00, 115.00]Serum creatinine mg/dl (median [IQR]) 0.70 [0.60, 0.90] 0.70 [0.60, 0.90] 0.70 [0.70, 0.90]Anti-Scl-70 positive = Yes (%) 1147 (33.1) 958 (35.6) 189 (24.5)CRP elevation = Yes (%) 639 (21.1) 490 (20.8) 149 (22.1)Platelet inhibitors therapy = Yes (%) 245 (7.1) 206 (7.7) 39 (5.1)Oral anti-coagulants therapy = Yes (%) 53 (1.5) 50 (1.9) 3 (0.4)Disclosure of Interests:None declared

During the current global outbreak of coronavirus disease 2019 (COVID-19), risk stratification of patients is of utmost importance. Currently, patients >65 years and those with pre-existing medical conditions such as cardiovascular disease, chronic respiratory disease or diabetes mellitus are considered at higher risk for severe disease.1 The Swiss Federal Office of Public Health, like similar authorities around the world, has additionally included patients on immunosuppressants in the high-risk group for developing severe COVID-19.2 However, at this moment we do not have enough evidence either to support or to reject this assumption. We report the case of a 57-year-old woman with systemic sclerosis (SSc) who developed COVID-19. Comorbidities were insulin-dependent type 2 diabetes mellitus and WHO grade I obesity. The anti-topoisomerase I antibody-positive patient was diagnosed with SSc in 2017. SSc-associated interstitial lung disease (SSc-ILD), with cough and exertion dyspnoea, was the leading organ manifestation, associated with symmetrical, non-erosive polyarthritis, and elevated acute phase reactants. Treatment with the anti-interleukin (IL) 6 receptor blocker tocilizumab, with 8 mg/kg body weight every 4 weeks intravenously, was started, leading to a good control of both …

Background:The gastrointestinal (GI) tract is frequently involved in systemic sclerosis (SSc). The University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA GIT 2.0) is validated to capture GI morbidity in patients with SSc (1). The routine clinical investigation of GI involvement in these patients is not standardized and there is no consensus about when and how frequently an esophagogastroduodenoscopy (EGD) should be performed.Objectives:The main aim of this study was to analyze the capacity of UCLA GIT 2.0 to identify patients with erosive esophagitis in an unselected, real-life SSc patients’ cohort. Secondary aim was to determine whether the UCLA GIT 2.0 could discriminate SSc patients for whom an expert rheumatologist would recommend an EGD.Methods:We selected patients fulfilling the ACR/EULAR 2013 criteria for SSc from the Zurich cohort, having completed at least once the UCLA GIT 2.0 questionnaire. We reviewed the medical charts of SSc patients from 2013 to 2019 and recorded data on EGD. We analyzed by univariable logistic regression several parameters, including UCLA GIT 2.0, considered as potentially associated with 1) the referral to EGD and 2) macroscopic esophagitis according to the Los Angeles criteria.Results:We identified 346 patients (82.7% female, median age 63 years, median disease duration 10 years, 23% with diffuse cutaneous SSc) satisfying the inclusion criteria, who filled in 940 UCLA GIT 2.0 questionnaires.From 940 visits, 31 were excluded because EGD was done within 3 months before completing the UCLA GIT 2.0. In the 909 remaining visits, EGD was recommended by the expert rheumatologists in 128 cases. In logistic regression, UCLA GIT 2.0 total score and some of its subscales, but also the modified Rodnan skin score (mRSS) and esophageal and stomach symptoms by past medical history, associated with the referral to EGD (Table 1).Table 1.Logistic regression of factors associated with referral to EGDOR (95% CI)p-valuemRSS1.04 (1.01 - 1.06)0.009Hemoglobin (Hb)1.00 (0.96 - 1.04)0.978Proton pump inhibitor (PPI)0.37 (0.12 - 1.15)0.086Esophageal symptoms3.37 (2.28 - 4.96)Stomach symptoms2.93 (2.02 - 4.26)Reflux subscale2.04 (1.52 - 2.73)Distention/bloating subscale1.53 (1.24 - 1.89)Social functioning2.20 (1.57 - 3.07)Emotional wellbeing1.42 (1.03 - 1.97)0.034Total score of UCLA GIT 2.02.27 (1.55 - 3.32)We found data on 177 EGD performed in 150 patients, meaning that 49 EGD were performed on indication by another physician. In logistic regression, mRSS and esophageal symptoms correlated with esophagitis, while neither the total ULCA GIT 2.0 score nor the reflux subscale or any of the other subscales showed an association with esophagitis (Table 2).Table 2.Logistic regression of factors associated with esophagitisOR (95% CI)p-valuemRSS1.09 (1.03 - 1.15)0.001Hb1.03 (0.99 - 1.06)0.126PPI0.52 (0.27 - 1.03)0.059Esophageal symptoms2.92 (1.29 - 6.61)0.010Stomach symptoms1.60 (0.80 - 3.21)0.183Reflux subscale1.07 (0.60 - 1.93)0.816Distention/Bloating subscale0.63 (0.39 - 1.01)0.054Social functioning0.65 (0.31 - 1.35)0.245Emotional wellbeing0.77 (0.36 - 1.61)0.483Total score of UCLA GIT 2.00.67 (0.28 - 1.60)0.367Conclusion:In a real-life setting, UCLA GIT 2.0 subscales (reflux, distention/bloating, social functioning, emotional wellbeing) and total score strongly associated with expert interpretation of gastroesophageal symptoms and consecutive referral to EGD. However, they showed no correlation with esophagitis on EGD. The main clinical association of esophagitis was the presence of esophageal symptoms.References:[1]Khanna D, et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 2009;61(9):1257-63.Disclosure of Interests:Norina Zampatti: None declared, Alexandru Garaiman: None declared, Suzana Jordan: None declared, Mike O. Becker: None declared, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis, Rucsandra Dobrota: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Carina Mihai: None declared

Background:Depression, anxiety and distress affect the quality of life of patients with systemic sclerosis (SSc) [1]. The Hospital Anxiety and Depression Scale (HADS) and Sense of Coherence 13-item scale (SOC-13, measuring comprehensibility, manageability and meaningfulness) are screening tools used in patients with different medical conditions. However, their validity, reliability and sensitivity to change in SSc patients has not been evaluated yet.Objectives:To examine the psychometric properties of HADS and its subscales HADS-A and HADS-D (measuring anxiety and depression symptoms, respectively), and unidimensional SOC-13 in a large cohort of Swiss SSc patients.Methods:Consecutive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc who completed the HADS, SOC-13, Short Form-36 Health Survey (SF-36) and Scleroderma Health Assessment Questionnaire (SHAQ) were included in a cross-sectional and longitudinal analysis. Cronbach’s α, split-half reliability and construct validity were measured. Sensitivity to change (Cohen’s d coefficient) was assessed in patients who worsened within 12±3 months, defined as occurrence of any of the following events: decline in forced vital capacity (FVC)≥10%, new diagnosis of interstitial lung disease (ILD) on high-resolution computed tomography (HRCT), progression of known ILD to >20% lung involvement on HRCT (ILD20), new-onset pulmonary hypertension (PH), increase in European Scleroderma Study Group activity index (EScSG-AI) >3 points, new active digital ulcers, increase in modified Rodnan skin score (mRSS) > 7 points.Results:Of 345 patients (aged 59.34±14.17, 82.9% female, 18.8% with diffuse cutaneous SSc, 47.6% anti-centromere Ab-positive, 23.5% anti-Scl-70 Ab-positive, 13% anti-U1RNP Ab-positive and 11.3% anti-RNA polymerase III Ab-positive) 85 participated with a second visit to the sensitivity to change analysis.Internal consistency was excellent for the HADS (Cronbach’s α=0.91; split-half reliability r=0.92), and very good for HADS-A, HADS-D and SOC-13 (Cronbach’s α=0.85-0.89; split-half reliability r=0.86-0.89).Regarding construct validity, all four scales showed a strong to very strong correlation to each other, as well as with the mental components of SF-36 (Spearman’s r=0.63-0.85). There was a moderate to strong correlation with the SHAQ (Spearman’s r=0.45-0.64).Regarding sensitivity to change: HADS-A showed a large to very large effect size (ES) for progression of ILD as assessed on HRCT and increase in EScSG-AI (Cohen’s d=1-1.63), and a very small to small ES for changes in FVC, DU and mRSS (Cohen’s d=0.02-0.45). HADS-D showed a large ES for changes in the ILD20, mRSS and EScSG-AI (Cohen’s d=0.82-1), and moderate ES for changes of FVC, ILD, PH, DU (Cohen’s d=0.1-0.49). SOC-13 showed generally a very small to small EF, except for change in mRSS (Cohen’s d=0.56).Conclusion:The HADS(A/D) and SOC-13 are valid and easy-to-use tools to detect depression, anxiety and distress in SSc. However, their sensitivity to change might be limited by the respective type of organ involvement and its impact on the patients’ psychological wellbeing.References:[1]Legendre C, Allanore Y, Ferrand I, Kahan A. Evaluation of depression and anxiety in patients with systemic sclerosis. Joint Bone Spine. 2005;72(5):408–411.Disclosure of Interests:Alexandru Garaiman: None declared, Carina Mihai: None declared, Rucsandra Dobrota: None declared, Suzana Jordan: None declared, Britta Maurer Grant/research support from: AbbVie, Protagen, Novartis, congress support from Pfizer, Roche, Actelion, and MSD, Speakers bureau: Novartis, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Mike-Oliver Becker: None declared