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The prevalence of meralgia paresthetica (MP), which is caused by compression of the lateral femoral cutaneous nerve (LFCN), has been increasing over recent decades. Since guidelines and large-scale studies are lacking, there are substantial regional differences in diagnostics and management in MP care. Our study aims to report on current diagnostic and therapeutic strategies as well as time trends in clinical MP management in Germany. Patients hospitalized in Germany between January 1, 2005, and December 31, 2018, with MP as their primary diagnosis were identified using the International Classification of Disease (ICD-10) code G57.1 and standardized operations and procedures codes (OPS). A total of 5828 patients with MP were included. The rate of imaging studies increased from 44% in 2005 to 79% in 2018 (p p p p p

Background Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition. Research Question Which factors determine the outcome of PH in COPD? Study Design and Methods We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH). Results The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes. Interpretation Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further. Trial Registry ClinicalTrials.gov; No.: NCT01347216 ; URL: www.clinicaltrials.gov

BACKGROUND: The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated. METHODS: Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses. RESULTS: All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools. CONCLUSION: While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:41 issue:7 pages:971-981 ispartof: location:United States status: published

BackgroundRisk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a three-stratum model to categorise risk as low, intermediate or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on four risk categories, with intermediate risk subdivided into intermediate-low and intermediate-high risk.MethodsWe analysed data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on World Health Organization functional class, 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed using Kaplan–Meier analyses, log-rank testing and Cox proportional hazards models.ResultsData from 1655 patients with PAH were analysed. Using the three-stratum model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined four-stratum risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the three-stratum model and in 49.2% with the four-stratum model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk.ConclusionsModified risk stratification using a four-stratum model based on refined cut-off levels for functional class, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original three-stratum model.

BACKGROUND: A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities. METHODS: We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities. RESULTS: The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities. CONCLUSIONS: Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:42 issue:1 pages:102-114 ispartof: location:United States status: published

In recent decades, the global incidence of aneurysmal subarachnoid hemorrhage (aSAH) has declined. However, significant regional differences exist. We present the first comprehensive analysis of time trends in the incidence of aSAH and case fatality in Germany.All patients hospitalized with aSAH in Germany between 2005 and 2018 were identified using International Classification of Disease, 10th Revision codes I60.0-I60.7.A total of 101,105 cases were included. The incidence of aSAH in Germany decreased at a mean annual rate of 0.5% (p = 0.003) from 8.9 per 100,000 population in 2005 to 8.2 in 2018. Over time, incidences of aSAH declined among patients younger than 55 years and patients aged 70-79 years, increased among ages 60-64 years, and remained stable in age groups 65-69 and 85-89 years. This corresponded to an increase in the mean age of aSAH onset from 55.6 (±14.3) to 59.0 (±14.0) years. Throughout the study period, the mean age of aSAH onset was higher in women compared to men (58.3 ± 14.4 years vs. 56.1 ± 14.1 years). There were no changes in in-hospital case fatality (16.2 vs. 16.6%, p = 0.18), but the duration of hospital stay increased significantly from 19.7 to 24.8 days (p lt; 0.001). The most frequent aSAH-associated aneurysm location was the anterior circulation throughout the entire study period.In Germany, the incidence of aSAH decreased between 2005 and 2018, especially in younger parts of the population. This may reflect effects of lifestyle adjustments most pronounced in younger age groups.

Objective To describe trends in outcomes among patients with idiopathic inflammatory myopathies (IIM) over two decades. Methods From 1997 to 2017, a total of 1079 IIM patients were documented in the National Database of the German Collaborative Arthritis Centers. Annual cross-sectional data on treatment, disease activity, patient-reported outcomes, hospitalization and employment were compared across the years. Information on phenotypes, organ manifestations and autoantibodies was collected for a subset to compare the assessment of global health, pain, fatigue and sleeping disorders. Results In 2017, significantly more IIM patients were assessed to be in low disease activity (94%) than in 1997 (59%), p p = 0.001), global health (p = 0.049), fatigue (p = 0.03) and sleeping disorders (p = 0.01) also improved since recording. Glucocorticoid use decreased from 84 to 58% (p Conclusion IIM patients report better outcomes than 20 years ago, along with good physician-reported disease control. Global health, fatigue and sleeping disorders are relevant patient-reported domains in IIM.

BackgroundSince 2015, the European pulmonary hypertension guidelines recommend the use of combination therapy in most patients with pulmonary arterial hypertension (PAH). However, it is unclear to what extent this treatment strategy is adopted in clinical practice and if it is associated with improved long-term survival.MethodsWe analysed data from COMPERA, a large European pulmonary hypertension registry, to assess temporal trends in the use of combination therapy and survival of patients with newly diagnosed PAH between 2010 and 2019. For survival analyses, we looked at annualised data and at cumulated data comparing the periods 2010–2014 and 2015–2019.ResultsA total of 2531 patients were included. The use of early combination therapy (within 3 months after diagnosis) increased from 10.0% in patients diagnosed with PAH in 2010 to 25.0% in patients diagnosed with PAH in 2019. The proportion of patients receiving combination therapy 1 year after diagnosis increased from 27.7% to 46.3%. When comparing the 2010–2014 and 2015–2019 periods, 1-year survival estimates were similar (89.0% (95% CI 87.2–90.9%) and 90.8% (95% CI 89.3–92.4%), respectively), whereas there was a slight but nonsignificant improvement in 3-year survival estimates (67.8% (95% CI 65.0–70.8%) and 70.5% (95% CI 67.8–73.4%), respectively).ConclusionsThe use of combination therapy increased from 2010 to 2019, but most patients still received monotherapy. Survival rates at 1 year after diagnosis did not change over time. Future studies need to determine if the observed trend suggesting improved 3-year survival rates can be confirmed.

BACKGROUND: Among patients meeting diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH), there is an emerging lung phenotype characterised by a low diffusion capacity for carbon monoxide (DLCO) and a smoking history. The present study aimed at a detailed characterisation of these patients. METHODS: We analysed data from two European pulmonary hypertension registries, COMPERA (launched in 2007) and ASPIRE (from 2001 onwards), to identify patients diagnosed with IPAH and a lung phenotype defined by a DLCO of less than 45% predicted and a smoking history. We compared patient characteristics, response to therapy, and survival of these patients to patients with classical IPAH (defined by the absence of cardiopulmonary comorbidities and a DLCO of 45% or more predicted) and patients with pulmonary hypertension due to lung disease (group 3 pulmonary hypertension). FINDINGS: The analysis included 128 (COMPERA) and 185 (ASPIRE) patients with classical IPAH, 268 (COMPERA) and 139 (ASPIRE) patients with IPAH and a lung phenotype, and 910 (COMPERA) and 375 (ASPIRE) patients with pulmonary hypertension due to lung disease. Most patients with IPAH and a lung phenotype had normal or near normal spirometry, a severe reduction in DLCO, with the majority having no or a mild degree of parenchymal lung involvement on chest computed tomography. Patients with IPAH and a lung phenotype (median age, 72 years [IQR 65-78] in COMPERA and 71 years [65-76] in ASPIRE) and patients with group 3 pulmonary hypertension (median age 71 years [65-77] in COMPERA and 69 years [63-74] in ASPIRE) were older than those with classical IPAH (median age, 45 years [32-60] in COMPERA and 52 years [38-64] in ASPIRE; p

BACKGROUND: Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition. RESEARCH QUESTION: Which factors determine the outcome of PH in COPD? STUDY DESIGN AND METHODS: We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH). RESULTS: The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes. INTERPRETATION: Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01347216; URL: www.clinicaltrials.gov. ispartof: CHEST vol:160 issue:2 pages:678-689 ispartof: location:United States status: published

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO

Additional file 1: Fig. S1. Immunomodulator treatment received at baseline according to HAQ-DI score assessments. Table S1. Results of the multistate model calibration on longitudinal patient-level data (transition intensities between the HAQ-DI states in function of covariates). Table S2. Results of a survival model calibration on longitudinal patient-level data (transition intensities between the organ states in function of covariates). Table S3. Univariate and multivariable Cox regression analysis of the HAQ-DI domains influencing mortality risk in patients with ≥ 1 HAQ-DI measurement.

Background The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. Previous studies from the United Kingdom and Spain have reported incidence rates of 1.75 and 0.9 per million, respectively. These figures, however, may underestimate the true incidence of CTEPH. Methods We prospectively enrolled patients newly diagnosed with CTEPH within 2016 in Germany. Data were obtained from the three German referral centers and from the German branch of COMPERA, a European pulmonary hypertension registry. The CTEPH incidence was calculated based on German population data, and patient characteristics and treatment patterns were described. Results A total of 392 patients were newly diagnosed with CTEPH within 2016 in Germany, yielding an incidence of 5.7 new cases per million adults. The (mean ± standard deviation) age was 63.5 ± 15.0 years; males and females were equally affected; 76.3% of the patients had a history of venous thromboembolism. A total of 197 (50.3%) patients underwent pulmonary endarterectomy. Almost all non-operated patients received targeted drug therapy, and 49 patients (25.1% of the non-operated patients) were treated with balloon pulmonary angioplasty. Conclusion The incidence of CTEPH in Germany 2016 was 5.7 per million adults and thus higher than previously reported from other countries. Half of the patients were operated while the remaining patients received medical or interventional therapies. Clinical trials registration http://www.clinicaltrials.gov NCT02660463 and NCT01347216.

Background:Nintedanib has shown to slow FVC decline by 41ml over 52 weeks in systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, the long-term effect of nintedanib treatment on ILD progression and mortality in SSc patients is so far unknown.Objectives:Here, the 52-week treatment efficacy of nintedanib was modeled and extrapolated on the long-term FVC course and survival in SSc-ILD patients from the European Scleroderma Trial and Research (EUSTAR) database.Methods:SSc patients from the EUSTAR database fulfilling the inclusion criteria of the SENSCIS trial (SSc classification criteria, ILD confirmed by imaging, disease duration of Results:Of the 236 included patients, 75% were females, 65% had diffuse cutaneous SSc. Mean age was 50.6 years, mean FVC 78.2%pred and DLCO 56.3%pred at time of inclusion. Mean FVC change after 12±3 months was -2.3 ±6.9%pred. These parameters were largely similar to the characteristics of the SENSCIS population.In the longitudinal follow up of this population, the natural course of FVC showed a total FVC decline of -16.3%pred over 5 years. With assumed SENSCIS effects (effects of nintedanib treatment reported in SENSCIS), the 5-year FVC decline was reduced to -10.3%pred (Figure 1).The reduced FVC progression translated into an improved survival. The natural 5-year survival of this SSc-ILD population was 88.2%. When extrapolating also a severe FVC decline early in the course, frequently terminated by early mortality of SSc patients excluding them from long-term outcome assessment, the estimated 5-year survival was reduced to 81.6%. When the SENSCIS effects on FVC were considered, the 5-year extrapolated survival was increased to 86.3% (Figure 2).Conclusion:Long-term experience of nintedanib treatment in SSc-ILD patients is lacking so far, therefore we modeled and extrapolated the 52-week treatment efficacy of nintedanib on the long-term FVC course and survival in SSc-ILD patients from the EUSTAR database. We could demonstrate a significant reduction of FVC decline by extrapolating the annual treatment effects of nintedanib from the SENSCIS trial from 1 to 5 years in EUSTAR. Translating these reductions of FVC decline into survival, the 5-year mortality rate was reduced from 18% to 13%.Disclosure of Interests:Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Merck Sharp & Dohme, Lilly, Consultant of: Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Grant/research support from: Boehringer Ingelheim, Dörte Huscher: None declared, Paolo Airò Speakers bureau: Boehringer Ingelheim, Consultant of: Bristol-Myers-Squibb, Novartis, Elisabetta Zanatta Speakers bureau: Boehringer Ingelheim, Actelion, GSK, Paid instructor for: GSK, Consultant of: Boehringer Ingelheim, GSK, Patricia Carreira Speakers bureau: Actelion, Boehringer Ingellheim, Janssen, GSK, Paid instructor for: Boehringer Ingelheim, Consultant of: AbbVie, Boehringer Ingelheim, VivaCell, Emerald Health Pharmaceuticals, Gesynta Pharma, Sanofi Genzyme, Grant/research support from: Roche, GSK, Yannick Allanore Consultant of: Honorarium received from Boehringer, MedsenicSanofi, Menarini, Grant/research support from: Grants received from Alpine, Ose Immunogenetics, Ulf Müller-Ladner Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Alessandro Giollo: None declared, Maria Rosa Pozzi: None declared, CAROLINA SOUZA MULLER Speakers bureau: Boehinger Ingelheim, Janssen, Roche, LIBBS, Bristol-Myers-Squib, Radim Bečvář Consultant of: Actelion, Boehringer Ingelheim, Michele Iudici: None declared, Dominik Majewski Speakers bureau: Boehringer Ingelheim - 2 x paid as a speaker, Armando Gabrielli Grant/research support from: Pfizer, CSL Behring, Margarida Alves Employee of: Boehringer Ingelheim, Nils Schoof Employee of: Boehringer Ingelheim International GmbH, Oliver Distler Speakers bureau: Boehringer Ingelheim, Medscape, IQone, Roche, Consultant of: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, Kymera Therapeutics, Lilly, Medac, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB, Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe

Background:There is renewed interest in the role of autoantibodies to predict outcomes in systemic sclerosis (SSc). Among the newly identified subsets, patients with limited cutaneous form (lcSSc) but anti-topoisomerase I antibodies (Scl70) positivity draw particular attention, and namely, assessing the risk of developing interstitial lung disease (ILD) —the main cause of death in SSc—to improve the management of Scl70-lcSSc patients.Objectives:We aimed to characterize patients with Scl70-lcSSc in the large multicenter European Scleroderma Trial and Research (EUSTAR) cohort.Methods:The EUSTAR database was locked in July 2019. We included all patients fulfilling 1980 ACR and/or 2013 ACR/EULAR criteria for SSc, with disease duration at database entry ≤3 yrs and known and stable skin form during the first 3 yrs. Patients with lcSSc were compared: Scl70-lcSSc (target group) vs. ACA-lcSSc and ANA-lcSSc (Step 1); and Scl70-lcSSc vs. Scl70-dcSSc (Step 2). In the ANA subgroup we included ANA+ patients with negative SSc-specific antibodies (Scl70, ACA, RNA polymerase III). In each step, we performed 5 generalized mixed models (GMM) for the risk of the new onset of ILD (defined by imaging), primary myocardial involvement (PMI), pulmonary hypertension (PH), “any severe” (ILD+PMI+PH+scleroderma renal crisis) and all-cause-mortality. An additional GMM assessed the risk of forced vital capacity (FVC) decline ≥10% vs. FVC value at ILD onset. Each GMM was adjusted for age, sex and confounders.Results:Overall, 1285 SSc patients were included: 1068 (83%) females, 860 (67%) lcSSc and 425 (33%) dcSSc. Among patients with lcSSc, 537 (62%) had ACA+, 194 (23%) Scl70+ and 129 (15%) ANA+; 425 patients had dcSSc and Scl70+. Median follow-up was similar in all 4 groups: 7.2 to 8.1 yrs.Step 1: At baseline, Scl70-lcSSc patients had significantly shorter time from Raynaud’s phenomenon (RP) to SSc onset, higher mRSS (5.8±4.8 vs. 4.3±4, p=0.001), and higher rate of articular and muscular involvement vs. ACA-lcSSc patients (Figure 1). No differences were found between Scl70-lcSSc and ANA-lcSSc comparing the aforementioned variables. ILD was more frequent in Scl70-lcSSc (46%) than in ACA-lcSSc (10%) and ANA-lcSSc (25%), as well as restrictive lung disease. GMM showed that Scl70-lcSSc carries a higher risk of ILD than both ACA-lcSSc (HR 4.55, 95%CI 3.23-6.67) and ANA-lcSSc (HR 2.17, 95%CI 1.39-3.45), with a rate of FVC decline ≥10% over time similar to the other limited forms. In Scl70-lcSSc patients the risk of “any severe” organ involvement was similar to ANA-lcSSc and higher than ACA-lcSSc (HR 1.89, 95%CI 1.40-2.50). In particular, Scl70-lcSSc shows a risk of PMI similar to ANA-lcSSc and lower than ACA-lcSSc; no differences regarding PH risk. The mortality risk in patients with Scl70-lcSSc was similar to the other limited forms’.Step 2: At baseline, time from RP to SSc onset was longer in patients with Scl70-lcSSc, with less frequent joint synovitis and tendon friction rubs vs. patients with Scl70-dcSSc. Conversely, the frequency of muscular, cardiac and pulmonary involvement was similar. The risk of ILD in Scl70-lcSSc patients was similar to Scl70-dcSSc, with a lower risk of FVC decline ≥10% over time. The risk of “any severe” involvement (HR 0.66, 95%CI 0.49-0.83), PMI and PH was lower and the mortality risk tended to be lower (HR 0.57, 95%CI 0.33-1.01, p=0.053) vs. Scl70-dcSSc.Conclusion:In our large multicenter EUSTAR cohort one quarter of lcSSc patients were Scl70+. We show a ranking for major organ involvement within lcSSc: Scl70 the most severe, ANA+ intermediate and ACA the milder form. Scl70-dcSSc patients present the most severe phenotype, and Scl70 positivity, more than the cutaneous subset, is strongly predictive of ILD, whereas other variables may influence progression. These results may provide new insight to improve the management of Scl70-lcSSc patients.Disclosure of Interests:Elisabetta Zanatta: None declared, Dörte Huscher: None declared, Paolo Airò: None declared, Alexandra Balbir-Gurman: None declared, Elise Siegert: None declared, Augusta Ortolan: None declared, Marco Matucci-Cerinic: None declared, Franco Cozzi: None declared, Gabriela Riemekasten: None declared, Anna-Maria Hoffmann-Vold: None declared, Oliver Distler Speakers bureau: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe, Armando Gabrielli: None declared, Stefan Heitmann: None declared, Nicolas Hunzelmann: None declared, Carlomaurizio Montecucco: None declared, Jadranka Morovic-Vergles: None declared, Camillo Ribi: None declared, Andrea Doria: None declared, Yannick Allanore: None declared

Pulmonary hypertension (PH) is a common complication of many chronic lung diseases, especially chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) [1]. In these conditions, the development of PH is associated with an aggravation of symptoms and an increase in mortality risk. In most patients with chronic lung disease, the haemodynamic severity of PH is mild to moderate, while some patients develop severe PH, which is presently defined by a mean pulmonary arterial pressure (mPAP) ≥35 mmHg or mPAP ≥25 mmHg in the presence of a cardiac index

Prognostisch ungunstige Faktoren sollen in Therapieentscheidungen bei rheumatoider Arthritis (RA) einbezogen werden. Es gibt kaum Daten uber die Haufigkeit der einzelnen Faktoren bei Patienten in der Routineversorgung. Krankheitsaktivitat (Disease Activity Score DAS28), Erosionen, Antikorper gegen citrullinierte Peptide oder Rheumafaktoren (ACPA/RF), vorheriges Therapieversagen, Entzundungsmarker sowie Funktionseinschrankungen (FFbH 5,1, 64 % waren ACPA/RF+, 13 % hatten Erosionen und 37 % einen FFbH 5,1 von 33 % auf 52 % und FFbH von 41 % auf 66 %. In der Kerndokumentation waren zwischen 47 % (DMARD naiv) und 82 % (≥2 vorherige DMARD-Therapien) ACPA/RF+. 5 bis 11 % hatten unter Therapie einen DAS28 > 5,1. Der Anteil von Patienten mit FFbH < 70 stieg mit der Zahl der Vortherapien von 26 % auf 50 %. Der mit zunehmender Zahl abgesetzter DMARD-Therapien steigende Anteil von Patienten mit ungunstigen Prognosefaktoren unterstreicht deren Bedeutung im Hinblick auf einen schwer zu kontrollierenden Krankheitsverlauf.

The initial inflammatory phase of fracture healing is of great importance for the clinical outcome. We aimed to develop a detailed time-dependent analysis of the initial fracture hematoma. We analyzed the composition of immune cell subpopulations by flow cytometry and the concentration of cytokines and chemokines by bioplex in 42 samples from human fractures of long bones

Background Since the introduction of biologic treatment in rheumatoid arthritis (RA), disease activity and treatment modalities have changed substantially. The current provision and developments in recent years are analyzed with annual data from the National Database of the Collaborative Arthritis Centers in Germany. Methods To analyze disease activity, diagnostics and treatment in RA patients in 2014 with regard to seropositivity and disease duration. Time trends from 2007-2014 are reported for disease activity (DAS28) distribution and biologic treatment. Results In 2014, a total of 8,084 RA patients were analyzed: 72 % were rheumatoid factor and/or ACPA positive, the mean age was 62 years and the mean disease duration 12 years. According to DAS28, 35.9 % were in remission, 19.2 % had low, 37.1 % moderate and 7.8 % high disease activity. An increase since 2007 was only observed in patients with a disease duration >2 years. Synthetic DMARDS were used for treatment in 78 %. Biologic treatment increased from 16 % (2007) to 27 % (2014). Especially those patients with a disease duration >5 years were treated more frequently with biologics. Seronegative patients had slightly less severe mean disease activity parameters. They were treated equally frequent with DMARDS but only half as often with biologics compared to seropositive patients. Conclusion The use of biologics in RA patients has increased since 2007; however this was not observed in patients with short disease duration. Early intensive treatment adaption seems justified to improve disease activity in the large portion of patients who do not reach low disease activity under conventional DMARDs.

Introduction The aim of the study was to evaluate the effect of endothelin-1 receptor antagonists (ETRAs) on skin fibrosis in systemic sclerosis (SSc) patients from the (EULAR Scleroderma Trials and Research) EUSTAR cohort. Methods SSc patients from the EUSTAR cohort with at least three visits (pre-study visit without ETRA treatment, baseline and follow-up visit with ETRA treatment) were included. The control group consisted of SSc patients with the same inclusion criteria, but without ETRA treatment. The primary endpoint was the comparison of the delta change of the modified Rodnan skin score (mRSS) between baseline and follow-up in the ETRA versus the control group. Results Data on 75 ETRA treated (68 bosentan, 1 sitaxentan, 6 ambrisentan) and 969 control patients were included. The delta change of mRSS was not significantly different between the ETRA group and the control group (n = 969; 0 (-2-1) vs. n = 75; 0 (-2-1); p = 0.4). Similarly, subgroup analysis on patients with diffuse, extended SSc disease (mRSS ≥16) did not show differences in the delta change of mRSS between the ETRA group and the control group (n = 125; −1 [-7-0] vs. n = 23; −1 [-7-2], p = 0.8). Likewise, diffuse SSc patients with mRSS 7-21 at baseline, reflecting recently identified enrichment criteria for clinical trials, did not show any difference between the ETRA and the control group (n = 219; −1 [-3-1] vs. n = 27; −1 [-3-2]; p = 0.5). Conclusions This controlled, observational, real-life cohort study with a large sample size did not show effects of ETRAs on skin fibrosis in patients with SSc.

Background:Rheumatoid arthritis (RA) is associated with increased systemic bone loss, leading to a high risk for fragility fractures. Especially anti-citrullinated protein antibody (ACPA) positivity is considered a risk factor for local bone erosions and systemic bone loss1.Objectives:The purpose of this study was to compare ACPA positive versus ACPA negative RA patients in terms of the prevalence of osteoporosis and fragility fractures and to identify differences in underlying risk factors that influence bone health.Methods:Rh-GIOP is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic rheumatic diseases or psoriasis treated with glucocorticoids (GC). In this cross-sectional analysis, we performed a matched-pair analysis, matching 114 ACPA positive to 114 ACPA negative RA patients according to age (5-year-steps), sex, and body mass index (BMI, 2-unit-steps). Descriptive analyses were performed, with values displayed as mean ± standard deviation for continuous variables. Non-parametric tests were used at a two-sided significance level of 5% to compare differences in underlying and potential risk factors without adjustment for multiple testing.Results:At same mean age (63.9 ±10.2 years) and BMI (27.9 ±5.6kg/m2), the matched groups had a female proportion of 82.5%. APCA positive patients had a significantly longer mean disease duration (13.9 vs 9.9 years, pConclusion:In a cross-sectional analysis of our cohort, the prevalence of osteoporosis and fragility fractures was similar between ACPA positive and ACPA negative RA patients, despite longer disease duration and GC-treatment in ACPA positive patients. This is remarkable since it implies that ACPA negative patients are at a similar risk for osteoporosis and associated fractures. Optimal management of disease activity with or without GCs may represent a mainstay in preventing disease-related comorbidities such as osteoporosis.References:[1]Steffen, U., Schett, G., & Bozec, A. (2019). How Autoantibodies Regulate Osteoclast Induced Bone Loss in Rheumatoid Arthritis. Frontiers in immunology, 10, 1483. doi:10.3389/fimmu.2019.01483Disclosure of Interests:Edgar Wiebe: None declared, Desiree Freier: None declared, Dörte Huscher: None declared, gloria dallagiacoma: None declared, Robert Biesen: None declared, Sandra Hermann: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.

Background:Rheumatic diseases are associated with increased systemic bone loss and fracture risk related to chronic inflammation, disease-specific, general and demographic risk factors as well as treatment with glucocorticoids (GC). Yet, there is evidence that GCs may, by adequately suppressing systemic inflammation, also have a positive effect on bone mineral density (BMD) and fracture risk1.Objectives:The purpose of this study was to investigate the prevalence of osteoporosis and fragility fractures in patients with inflammatory rheumatic diseases and to analyze the impact that treatment with GCs, other known risk factors and preventive measures have on bone health in these patients.Methods:Rh-GIOP is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic inflammatory rheumatic diseases and psoriasis treated with GCs. In this cross-sectional analysis, we evaluated the initial visit of 1091 patients. A multivariate linear regression model with known or potentially influential factors adjusted for age and sex was used to identify predictors of BMD as measured by dual-energy X-ray absorptiometry (DXA). Multiple imputation was applied for missing baseline covariate data.Results:In the total cohort of 1091 patients (75% female of which 87.5% were postmenopausal) with a mean age of 62.1 (±13.2) years, the prevalence of osteoporosis by DXA was 21.7%, while fragility fractures have occurred in 31.2% of the study population (6.7% vertebral, 27.7% non-vertebral). Current GC therapy was common (64.9%), with a median daily dose of 5.0mg [0.0;7.5], a mean life-time total GC dose of 17.7g (±24.6), and a mean GC therapy duration of 7.8 years (±8.5). Bisphosphonates were the most commonly used anti-osteoporotic drug (12.6%).Multivariate analysis showed that BMD as expressed by the minimum T-Score at all measured sites was negatively associated with higher age, female sex and menopause as well as Denosumab and Bisphosphonate treatment. A positive association with BMD was found for body mass index as well as current and life-time (cumulative) GC dose. While comedication with proton-pump-inhibitors significantly predicted low bone mass, concomitant use of non-steroidal anti-inflammatory drugs showed a positive association with BMD. Of the measured bone-specific laboratory parameters, higher alkaline phosphatase levels were determinants of low DXA-values, while the association was positive for gamma-glutamyltransferase.BMD was neither predicted by duration of GC treatment nor by treatment with disease modifying anti-rheumatic drugs.Predictive variables for BMD differed at the respective anatomical site. While treatment with Denosumab predicted low bone mass at the lumbar spine and not at the femoral neck, the opposite was true for health assessment questionnaire (HAQ) score. Current and life-time GC-dose as well as direct sun-exposure of more than 30 minutes daily were positively associated with bone mass at the femoral sites only.Conclusion:This cross-sectional analysis of a prospective cohort study quantified the prevalence of osteoporosis and identified predictive variables of BMD in patients with rheumatic diseases.Multivariate analyses corroborated low BMD to be predicted by traditional factors like age, female sex and menopause but showed current and well as life-time GC dose to be positively associated with BMD in our cohort of patients with chronic inflammatory rheumatic diseases. This suggests that optimal management of disease activity with GCs might be beneficial in order to avoid bone loss due to inflammation.References:[1]Güler-Yüksel et al. “Glucocorticoids, Inflammation and Bone.” Calcified Tissue International (January 08 2018).Disclosure of Interests:Edgar Wiebe: None declared, Desiree Freier: None declared, Dörte Huscher: None declared, Robert Biesen: None declared, Sandra Hermann: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.

Background Several studies have consistently showed that the extent of skin involvement has a major impact on disease prognosis in the diffuse cutaneous subtype of systemic sclerosis. The large majority of the ongoing clinical trials aim at identifying efficient drug in this subset. By contrast, little is known about the limited cutaneous subset (LcSSc) and the translation of the data coming for DcSSc to LcSSc is uncertain. Objectives Therefore, our aim was to investigate skin and lung involvement trajectories of LcSSc patients using the large EUSTAR registry. Methods We analysed the longitudinal data extracted from the EUSTAR cohort collected before February 2017. Worsening of skin fibrosis was defined by an increase in modified Rodnan skin score (mRSS) >3.5 points from baseline to 2nd visit. Interstitial lung disease (ILD) was defined by any fibrosis on imaging (X-ray/computed tomography). Worsening of ILD was defined by a decrease of FVC >10% from baseline to 2nd visit. For predicting models, predictors with p Results 8013 LcSSc were included with a mean follow-up of about 3.3±3.7 years. At baseline, mean ±SD mRSS was 6±5 and ILD was present in 28.4% of all patients. Worsening of skin fibrosis was observed in 6.4% (19/298), 7.8% (97/1248) and 9.8% (289/2957) of LcSSc patients at 6, 12 and 24 months follow-up respectively. In multivariate analysis, variables predicting skin fibrosis progression were elevated European Scleroderma Study Group activity index (EScSG-AI) (OR [95 IC]: 1.22 [1.05–1.4], p=0.007) for 12 months progression and EScSG-AI (1.24 [1.13–1.38], p Worsening of ILD was observed in 11.7% (23/196) and 19.9% (65/326) of LcSSc patients with ILD at baseline, at 12 and 24 months follow-up respectively. In multivariate analysis, variables predicting ILD progression at 24 months were EScSG-AI >3 (OR [95 IC]: 3.8 [1.51–9.56], p=0.005), FVC (1.03 [1.01–1.04], p Conclusions It appears that only few LcSSc patients progress for skin fibrosis ; this limits the use of mRSS in this subset and the potential of anti-fibrotic drugs of skin disease. However, a substantial rate of ILD progression was identified as well as relevant predictors. These results support the inclusion of LcSSc patients in SSc-ILD trials evaluating anti-fibrotic drugs. Our predictive models will be helpful to define enriched population in future clinical trials. Acknowledgements: This work was supported by an unrestricted grant from INVENTIVA Disclosure of Interest None declared

The 2015 European pulmonary hypertension (PH) guidelines propose a risk stratification strategy for patients with pulmonary arterial hypertension (PAH). Low-, intermediate- and high-risk strata are defined by estimated 1-year mortality risks of 10%, respectively. This risk assessment strategy awaits validation. We analysed data from patients with newly diagnosed PAH enrolled into COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based PH registry. An abbreviated version of the risk assessment strategy proposed by the European PH guidelines was applied, using the following variables: World Health Organization functional class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right atrial pressure, cardiac index and mixed venous oxygen saturation. Data from 1588 patients were analysed. Mortality rates were significantly different between the three risk strata (p, The risk stratification strategy proposed by the current European PH guidelines allows accurate survival prediction http://ow.ly/KsWk30c46nK

Background Poor prognostic factors (PPF) are used as decision-criteria for treatment strategies in patients with rheumatoid arthritis (RA). However, their definition is based on the outcome of rapid radiologic progression. Objectives To investigate the impact of PPF in RA on achieving low disease activity (LDA) at follow-up. Methods We performed a collaborative analysis of three large German RA cohorts. Patients under routine care were either DMARD-naive (n=991, early arthritis cohort CAPEA), on 1st conventional synthetic (cs)DMARD (n=2,547, National Database of the German Arthritis Centres (NDB)), or switching to a 2nd (n=1,959) or a 3rd DMARD (n=1,854, both biologics register RABBIT). Disease activity based on DAS28, autoantibody positivity (RF+/ACPA+), erosions, disability (HAQ≥1.2) and intake of glucocorticoids (>5mg/d) were evaluated as PPF at baseline. The outcome was DAS28 at 0, 3, 6 and 12 months. With multinomial logistic regression analyses, predictors of either LDA (DAS28 Results Patients had a mean age of 57 to 60 years; 63% of DMARD-naive patients and 71–72% of all others were female. Disease duration was 13 weeks in early RA (CAPEA) and 5–8 years in other cohorts. Patients with more treatment failures had more often PPF (not shown). The figure shows the course of disease activity stratified by baseline DAS28, erosions and RF/ACPA. Values of DAS28 at baseline did not differ depending on presence/absence of erosions and autoantibodies. In all cohorts, irrespective of maintaining or escalating the initial treatment, patients with or without erosions and autoantibodies had similar DAS28 outcomes, whereas patients with moderate or high baseline DAS28 had higher disease activity during follow-up. The proportion of patients that did not achieve LDA at 12 months was 46% in DMARD-naive, 34% on 1st DMARD, 47% switching to 2nd and 49% switching to 3rd DMARD. In the multinomial model, a 1-unit increase in DAS28 was associated with a decreased probability to achieve LDA in all cohorts (table). In contrast, autoantibodies (OR from 0.8 to 1.3) and erosions (OR from 0.8 to 1.6) had no impact on achieving LDA at month 12 or on treatment escalation. The latter applied for DAS28 (OR from 0.9 to 1.5) and HAQ (OR from 0.7 to 1.2) regarding only treatment escalation. Conclusions Although autoantibodies and erosions were associated with treatment failure, their absence did not predict LDA. Instead, baseline disease activity, functional status and glucocorticoid use may be more useful to guide treatment strategies when LDA is the target. Disclosure of Interest Y. Meissner Grant/research support from: CAPEA: funded by an unconditional grant from Pfizer. NDB: funded by unconditional grants from the German Collaborative Arthritis Centres and from a consortium of 11 pharmaceutical companies to the German Academy for Continuing Medical Education in Rheumatology. RABBIT: supported by a joint, unconditional grant from AbbVie, BMS, Celltrion, MSD, Pfizer, Roche, Samsung and UCB., K. Albrecht: None declared, A. Richter Consultant for: Pfizer, L. Baganz: None declared, D. Huscher: None declared, M. Schneider Grant/research support from: Abbvie, Chugai, UCB, Consultant for: Abbvie, Astra-Zeneca, BMS, Boehringer-Ingelheim, Chugai, Lilly, MSD, Pfizer, Roche, Sanofi-Aventis, UCB, A. Strangfeld Speakers bureau: BMS, MSD, Pfizer, Roche, Sanofi-Aventis, A. Zink Speakers bureau: AbbVie, BMS, MSD, Pfizer, Roche, UCB

Background Idiopathic inflammatory myopathies (IIM) are associated with considerable morbidity, primarily related to severe muscle weakness and visceral involvement, resulting in disability and impaired quality of life1. Results from the OMERACT Myositis Special Interest Group indicate that there is insufficient knowledge on patient-reported outcomes (PROs) in IIM2. Objectives To analyse the association between organ involvement and PROs in IIM patients, taking the presence of autoantibodies into account. Methods Data of IIM patients, recorded in the National Database of the German collaborative arthritis centres between 2007 and 2014, were analysed. Physician-reported data on myositis disease phenotypes, organ involvement and antibody status were linked with PROs on functional status (FFbH, range 0–100, 100 indicating full capability), and numerical rating scales (0–10) for pain, fatigue, general health, physical and emotional well-being and coping. Multivariable linear regression analysis was used to investigate the impact of phenotype, organ involvement and autoantibodies on PROs, adjusted for sex, age and disease duration. Results A total of 142 IIM patients - 60 polymyositis (PM), 46 dermatomyositis (DM), 15 antisynthetase syndrome (ASS), 12 overlap (OL), 9 others - with mean disease duration of 7.4 years were included. 85% showed muscular, 36% skin involvement, 22% arthritis, 28% interstitial lung disease, 17% dysphagia and 9% cardiomyopathy. Visceral (lung, cardiac or gastrointestinal) manifestation was present in 46% (PM), 54% (DM), 100% (ASS), and 80% (overlap). While moderate to severe (4–10) fatigue was predominately reported in overlap (64%) and ASS (70%), pain was more frequent in overlap (55%) and emotional discomfort was reported most frequently in ASS (57%). For all PROs, worse outcomes were documented in patients with visceral manifestation. Myositis-specific autoantibodies, predominantly Anti-Jo1, were present in 63% of the patients, and were associated with more frequent visceral manifestation (73% vs. 46%), especially interstitial lung disease (50% vs. 15%), and arthritis (32% vs. 13%), but less skin involvement (26% vs. 49%). DM and PM subtypes showed almost identical coefficients for fatigue, physical well-being, general health and coping, while PM was associated with higher emotional strain. Pulmonary hypertension had a severe impact on pain, functional status and daily activities. Cardiomyopathy was associated with impaired general health, arthritis with poorer scores for coping, physical and emotional well-being. Conclusions IIM patients with distinct subtypes differ considerably regarding the frequency of organ involvement and self-reported dimensions of disease burden. Anti-Jo1 positivity is associated with higher visceral organ involvement and arthritic manifestations and may therefore also indicate a higher patient-reported disease burden. References Marie I. Curr Rheumatol Rep 2012;14:275–85. Regardt M et al. Report from OMERACT 12. J Rheumatol. 2015;42:2492–5. Acknowledgements The database is funded by unconditional grants from the German Collaborative Arthritis Centres and from a consortium of 11 pharmaceutical companies to the German Academy for Continuing Medical Education in Rheumatology. Disclosure of Interest None declared

Background A consensus on DU definition in SSc has been recently reached (1),while for their evaluation,classification and categorisation it is still missing. Objectives To identify in SSc a set of essential items for DU evaluation, to assess if the existing DU classification (2) was useful and feasible in clinical practice, and to investigate if the DU categorisation (3) was preferred to the simple division of DU in recurrent and not recurrent. Methods The DU Desscipher items that reached >60% of completion rate were administered to EUSTAR centres via online survey.These items were: DU distal to the proximal interphalangeal joints, recurrent DU, DU history, infection, gangrene, amputation, total number of DU, number of new DU, number of healed DU, number of DU defined as loss of tissue, number of DU due to calcinosis and number of DU due to digital pitting scars (DPS).Questions about feasibility and usefulness of the existing DU classification (DU due to DPS, to loss of tissue, derived from calcinosis and gangrene) (2) and newly proposed DU categorisation (episodic, recurrent and chronic) (3) were also administered. Results All Desscipher and 82/194 EUSTAR centres (42.3%) completed the questionnaire.Out of 27 items selected for the Desscipher study, those scored by>70% of participants as essential and feasible for DU evaluation in clinical practice were only the following: number of DU defined as a loss of tissue (level of agreement 91.1%), recurrent DU (84%) and number of new DU (74.4%).For 64.6% of the centres,the classification of DU was considered useful and feasible in clinical practice.Moreover, 80.3% of the centres preferred the categorization of DU in episodic,recurrent and chronic. Conclusions For clinical practice, EUSTAR centres identified only three essential items for DU evaluation and considered useful and feasible the proposed classification and categorisation of DU.The set of items needs to be further validated by Delphi voting in order to implement its use in clinical practice while further implementation of DU classification and categorisation is warranted. References Suliman Y et al.Preliminary musculoskeletal ultrasound (MSUS) ulcer definition does not correlate with visual observation in systemic sclerosis (SSc) patients. J. Scleroderma Relat. Disord.2017(in press). Amanzi L et al.Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions. Rheumatology (Oxford) 2010;49:1374–82. Matucci-Cerinic M et al.Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry. Ann Rheum Dis. 2016;75:1770–6. Disclosure of Interest None declared

Background— For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). Methods and Results— We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival ( P =0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant ( P =0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. Conclusions— The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01347216.

Fehlbildungen des Herzens und der herznahen Gefase (AHF) gehoren zu den haufigsten kongenitalen Anomalien. Aufgrund der verbesserten interdisziplinaren Betreuung erreichen nun etwa 90 % der AHF-Patienten das Erwachsenenalter. Bei bis zu 10 % dieser Patienten besteht oder entwickelt sich eine pulmonale arterielle Hypertonie (PAH), die die Belastungsfahigkeit und Prognose verschlechtert. Daten zur Versorgungssituation der Patienten mit PAH-AHF sind nur eingeschrankt verfugbar. Das Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA, ClinTrials.gov Identifier NCT01347216) dokumentiert prospektiv Patienten ab 18 Jahren mit allen Formen der pulmonalen Hypertonie, sofern sie mit PAH-spezifischen Medikamenten behandelt werden (mittlere Beobachtungszeit aktuell 40 Monate). Zum 16. November 2012 hatten 8 % von insgesamt 3642 Patienten eine PAH-AHF, von denen 104 ausfuhrlich in einem separaten Modul beschrieben wurden. Im Mittel waren sie 39 Jahre alt (39 %) Manner, hatten eine mittlere 6-Minuten-Gehstrecke von 370 ± 102 Metern, und wurden in NYHA-Funktionsklasse I und II in 39 %, III in 59 %, und IV in 3 % eingestuft. Die mittlere Lebensqualitat auf der visuellen Analogskala (EQ-5 D, 0 bis 100) lag bei 51. Die PAH-AHF-Patienten wurden zu 80 % mit einer Monotherapie behandelt, zu 9 % mit Kombinationen bzw. erhielten in 11 % keine PAH-Medikamente. Nur 20 % erhielten eine orale Antikoagulation. Die mittlere Uberlebensrate nach 4 Jahren lag bei „inzidenten“ Patienten (PAH-AHF seit Registerbeginn neu diagnostiziert) bei 79 %, verglichen mit 72 % bei idiopathischer PAH (IPAH). Patienten mit PAH-AHF sind ausweislich der Registerdaten eingeschrankt belastungsfahig und haben eine stark verminderte Lebensqualitat. Sie werden seltener als IPAH-Patienten mit Kombinationen bzw. oraler Antikoagulation behandelt, ihre Uberlebensrate ist jedoch hoher.

Background METARTHROS (Metabolic impact on joint and bone disease) is a nationwide German network to investigate the overlap between inflammatory and metabolic diseases. The objective of this study was to compare the body mass index (BMI) distribution in patients with early and established rheumatoid arthritis (RA) with data from the general population, and to evaluate the association of BMI with patient characteristics and clinical markers. Methods The BMI distribution was examined with data collected at inclusion of patients in the early arthritis cohort CAPEA, the biologics register RABBIT, and the National database of the German Collaborative Arthritis Centers. A data source with a representative sample of the German population (German Ageing Survey) was used as a comparator. BMI categories of

Humane Immunglobuline (IG, uberwiegend IgG) werden zur Substitutionstherapie bei Patienten mit angeborenen (primaren) Immundefekten (PID), sowie Patienten mit sekundaren Immundefekten (SID), vor allem bedingt durch multiples Myelom oder chronisch lymphatische Leukamie angewendet. Ein weiteres Einsatzfeld besteht in der Immunmodulation bei neurologischen Autoimmunerkrankungen (NAID) wie Guillain-Barre-Syndrom, chronisch inflammatorisch demyelinisierende Polyneuropathie (CIDP) und multifokaler motorischer Neuropathie (MMN). Derzeit sind 16 IG-Praparate sind in Deutschland fur die intravenose oder subkutane Anwendung zugelassen. Aktuelle Daten zur Anwendung dieser Praparate werden derzeit in der SIGNS-Studie (Assessment of immunoglobulins in a long-term non-interventional study) in derzeit ca. 50 Studienzentren erfasst. In dieser nicht-interventionellen, prospektiven, offenen Versorgungs­forschungs­studie werden 550 Patienten mit bestehender oder neu initiierter Ig-Therapie hinsichtlich Therapiemuster (Praparatewahl, Dosierung etc.), Wirksamkeit (z. B. Infektrate bei PID und SID, Funktionalitat bei NAID), Vertraglichkeit, Lebensqualitat und Therapiekosten uber zwei Jahre beobachtet. Diese groste Studie ihrer Art soll zur Therapieoptimierung betroffener Patienten beitragen.

Abbreviated versions of the risk stratification strategy of the European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines have been recently validated in patients with pulmonary arterial hypertension. We aimed to investigate their prognostic value in medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients from the COMPERA registry, which collects six variables of interest (World Health Organization Functional Class, 6-min walk distance, brain natriuretic peptide, right atrial pressure, cardiac index and mixed venous oxygen saturation).We included patients with at least one follow-up visit, no pulmonary endarterectomy and at least three of the six variables available, and classified the patients into low-, intermediate- and high-risk groups. As a secondary analysis, the number of noninvasive low-risk criteria was counted. The association between risk assessment and survival was evaluated.Data from inclusion and follow-up (median 7 months) visits were available for 561 and 231 patients, respectively. Baseline 1- and 5-year survival estimates were significantly different (p

PAH patients reaching a low risk profile with targeted therapies have an excellent long-term survivalhttp://ow.ly/RBjo30i6N57

Objectives: To determine the prevalence of anti-Ku antibodies in 625 patients with systemic sclerosis (SSc) from six European rheumatological centres and to evaluate their clinical and serological characteristics. Methods: Sera of 625 consecutive patients with either limited cutaneous or diffuse cutaneous SSc were tested for antibodies to Ku antigen together with other extractable nuclear antigens by counterimmunoelectrophoresis. A case–control design with calculation of bootstrap 95% confidence intervals derived from anti-Ku negative control patients was used to evaluate clinical associations of anti-Ku antibodies. Sera from anti-Ku positive patients with SSc and a control group were additionally tested by immunofluorescence on Hep-2 cell substrates and line immunoassay. Results: Anti-Ku antibodies were found in the sera of 14/625 (2.2%) patients with SSc. Of 14 anti-Ku positive patients with SSc, 10 had no other anti-extractable nuclear antigen (ENA) antibodies detected by counterimmunoelectrophoresis. Using a case–control study design, anti-Ku antibodies were significantly associated with musculoskeletal manifestations such as clinical markers of myositis, arthritis and joint contractures. In addition, a significant negative correlation of anti-Ku antibodies was found with vascular manifestation such as fingertip ulcers and teleangiectasias. There was a striking absence of anti-centromere antibodies as well as anti- polymyositis (PM)/scleroderma (Scl) antibodies in patients that were anti-Ku positive. As expected, anti-Scl70 and punctate nucleolar immunofluorescence patterns were present only in single cases. Conclusion: This is the largest cohort to date focusing on the prevalence of anti-Ku antibodies in patients with SSc. The case–control approach was able to demonstrate a clinically distinct subset of anti-Ku positive patients with SSc with only relative clinical differences in skeletal features. However, the notable exceptions were signs of myositis. This shows the importance of anti-Ku antibody detection for the prediction of this specific clinical subset.

Background: While targeted therapies are available for idiopathic pulmonary arterial hypertension (IPAH), evidence based treatment recommendations for pulmonary hypertension (PH) associated with heart failure and preserved ejection fraction (HFpEF) are lacking. Methods and Results: Out of 5,935 patients in the prospective COMPERA registry, we analyzed patients with “typical” IPAH (n=421, ≤2 of the following risk factors: BMI >30 kg/m2, hypertension, CAD, diabetes and atrial fibrillation at the time of diagnosis), “atypical” IPAH (n=139, >2 risk factors) or PH-HFpEF (n=226) who received targeted PH therapies. Patients with PH-HFpEF, when compared to “typical” and “atypical” IPAH were older (73±8 vs. 62±17 and 71±9 years), had a higher BMI (30 vs. 26 and 32 kg/m2), and more comorbidities (98% vs. 73% and 100%, all p Conclusions: Despite almost identical alterations of pulmonary artery pressure and cardiac output, patients with PH-HFpEF differed with respect to age, comorbidities and certain hemodynamic features when compared to “typical” or “atypical” IPAH. All groups responded to targeted PH therapy, however tolerability and efficacy of PH drugs were reduced in patients with PH-HFpEF while survival was not different.

Background Pulmonary hypertension (PH) is a common finding in patients with chronic fibrosing idiopathic interstitial pneumonias (IIP). Little is known about the response to pulmonary vasodilator therapy in this patient population. COMPERA is an international registry that prospectively captures data from patients with various forms of PH receiving pulmonary vasodilator therapies. Methods We retrieved data from COMPERA to compare patient characteristics, treatment patterns, response to therapy and survival in newly diagnosed patients with idiopathic pulmonary arterial hypertension (IPAH) and PH associated with IIP (PH-IIP). Results Compared to patients with IPAH (n = 798), patients with PH-IIP (n = 151) were older and predominantly males. Patients with PH-IIP were treated predominantly with phosphodiesterase-5 inhibitors (88% at entry, 87% after 1 year). From baseline to the first follow-up visit, the median improvement in 6MWD was 30 m in patients with IPAH and 24.5 m in patients with PH-IIP (p = 0.457 for the difference between both groups). Improvements in NYHA functional class were observed in 22.4% and 29.5% of these patients, respectively (p = 0.179 for the difference between both groups). Survival rates were significantly worse in PH-IIP than in IPAH (3-year survival 34.0 versus 68.6%; p

Introduction: COMPERA is a European registry that prospectively enrols patients with various forms of pulmonary hypertension (PH) receiving targeted therapy. Aims and objectives: We compared patient characteristics, haemodynamics, treatment patterns and outcomes of patients with severe PH due to lung disease and patients with idiopathic pulmonary arterial hypertension (IPAH). Methods: Data were analysed from patients enrolled within 6 months of newly diagnosed PH into COMPERA until February 2015. Results: 1,472 patients were eligible for this analysis: IPAH, n=1,047; PH due to chronic obstructive lung disease (PH-COPD), n=260; and PH due to interstitial lung disease (PH-ILD), n=165. As shown in the table, all patient groups were characterized by severe PH and severe functional impairment. All patients received PH targeted therapies with pulmonary vasodilators; patients with PH due to lung disease mostly (90%) with PDE5i monotherapy. Survival rates at 1, 2 and 3 years were 91.7%, 81.5% and 70.7% in IPAH; 86.6%, 76.5% and 58.8% in PH-COPD; and 73.3%, 51.2% and 34.1% in PH-ILD (p Conclusions: In the COMPERA registry patients with PH due to lung disease presented with severe haemodynamic and functional impairment. Most patients received PDE5i-monotherapy. Despite targeted therapy patients with PH-COPD or PH-ILD had a significant worse survival than patients with IPAH. The effects of PH therapy on symptoms and outcomes in these patients require further studies.

The National Database of the German Collaborative Arthritis Centres is the most important source for the evaluation of current health care for German rheumatology patients. Since 1993, all outpatients with inflammatory rheumatic diseases treated in one of 24 arthritis centres have been recorded once a year using a clinical record form and a patient questionnaire. The aim is to gain knowledge on the outcomes and the medical, social and economic consequences of inflammatory rheumatic diseases in the real world, and to monitor continuously the current state and trends in health care. Data from more than 200,000 patients with inflammatory rheumatic diseases from 11 years (1993-2003) are available, making it possible to analyse even very rare diseases with a sufficient numbers of cases. Selected results on the health care situation, practice variation in rheumatology and the burden of illness in various diseases are reported.

Glucocorticoide (GC) sind unverzichtbarer Bestandteil einer zeitgemasen Behandlung in der Rheumatologie. Aufgrund des schnellen Wirkungseintritts und des hohen antiinflammatorischen Potentials sind sie in vielen Fallen unverzichtbar. Dies gilt trotz des bekannten Spektrums an unerwunschten Wirkungen und trotz einer eher bescheidenen Evidenz aus kontrollierten klinischen Studien. Umso bedeutsamer sind in dieser Situation Ergebnisse aus Beobachtungsdaten, die sowohl Auskunft geben uber typische Therapieentscheidungen von Rheumatologen im Hinblick auf die Verordnung von GC und die Kombination mit anderen Medikamenten als auch im Hinblick auf die Vermeidung der wichtigsten unerwunschten Wirkung, der GCinduzierten Osteoporose. Diese Daten liefert die Kerndokumentation der Rheumazentren. Sie zeigt als Querschnitt durch die rheumatologische Versorgung, dass 60% der Patienten mit rheumatoider Arthritis unter einer Therapie mit GC stehen, 85% davon mit einer Dosierung bis zu 7,5 mg/d. GC ersetzen nicht die Therapie mit DMARDs sondern sie werden verstarkt in Kombination mit neueren oder als besonders wirksam geltenden DMARDs eingesetzt, was die Orientierung der Therapie am Schweregrad der Krankheit unterstreicht. Die Variationsbreite zwischen den rheumatologischen Einrichtungen hinsichtlich des Einsatzes von GC ist gros und verdeutlicht die insgesamt ungesicherte empirische Evidenz. Hinsichtlich der GC-induzierten Osteoporose wird unter Rheumatologen eine umfangreiche, risikoadaptierte Therapie vorgenommen. Zwei Drittel der Patienten unter GC-Therapie erhalten eine Osteoporoseprophylaxe, Hochrisikogruppen deutlich mehr. Die Daten unterstreichen den hohen Stellenwert der GC in der modernen Rheumatherapie.

Die Versorgungsforschung bildet einen der funf Arbeitsbereiche im Kompetenznetz Rheuma. Sie befasst sich mit Fragen der Struktur und der Ergebnisse rheumatologischer Versorgung. Am Beispiel der rheumatoiden Arthritis werden ausgewahlte Forschungsergebnisse versorgungsbezogener Projekte dargestellt. Dabei wird auf die Kriterien fur die Einbeziehung von Krankheitsbildern in neue gesundheitspolitische Modelle („Disease Management”) eingegangen. Die durch die Kerndokumentation der Rheumazentren und versorgungsbezogene Kohortenstudien gewonnenen Daten zeigen die rheumatoide Arthritis als chronisch-progrediente Krankheit mit hoher subjektiver und objektiver Krankheitslast und erheblichen okonomischen Belastungen. Grosse Unterschiede in der Behandlung bestehen zwischen rheumatologisch spezialisiertem und nicht spezialisiertem Bereich. Neben der Evidenz aus kontrollierten klinischen Studien gibt es erste Belege aus Beobachtungsdaten, dass diese Differenzen mit unterschiedlichen Krankheitsfolgen verbunden sind. Das Potential fur Verbesserung ist hoch. Praxisvariation innerhalb der Rheumatologie ist Ausgangspunkt fur Massnahmen zum Qualitatsmanagement. Die Beteiligung der Rheumatologie an neuen Versorgungskonzepten bietet die Chance, die Leistungsfahigkeit einer rheumatologisch sachverstandigen Versorgung weiter unter Beweis zu stellen und bewahrte Formen der Kooperation auszubauen.