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ZusammenfassungDurch das COVID-19-Register (www.covid19-rheuma.de) der Deutschen Gesellschaft für Rheumatologie erfolgte erstmalig die Erfassung und systematische Evaluation einer viralen Infektion bei Patienten mit entzündlich rheumatischen Erkrankungen (ERE). Hierdurch war und ist eine schnelle Generierung von wissenschaftlichen Daten möglich, welche helfen, die Betreuung von Patienten mit ERE im Rahmen der Pandemie zu verbessern. Neben der Bestätigung allgemeiner Risikofaktoren – auch für Patienten mit ERE – wie Patientenalter und Komorbiditäten (z. B. kardiovaskuläre, chronische Lungen- und Nierenerkrankungen) konnten die Einnahme von Glukokortikoiden und die Krankheitsaktivität der rheumatischen Erkrankung als krankheitsspezifische Risikofaktoren für die Notwendigkeit einer stationären Behandlung wegen COVID-19 identifiziert werden. Auswertungen der kontinuierlich wachsenden Kohorte von Patienten mit entzündlich rheumatischen Erkrankungen und einer COVID-19-Infektion erlauben, Handlungsempfehlungen für die Betreuung der Patienten auf eine bessere Evidenz zu stützen. Die Kooperation mit internationalen rheumatologischen Registern (z. B. europäisches COVID-19-Register für ERE) ermöglicht Analysen aggregierter Kohortendaten von Patienten mit entzündlich rheumatischen Erkrankungen und einer SARS-CoV-2-Infektion für internationale Vergleiche und statistisch noch besser abgesicherte Aussagen.

ObjectivesSystemic sclerosis is a heterogeneous, multisystem disease. It can occur at any age, but most patients develop the disease between the age of 40 to 50 years. There is controversial evidence on whether/how the age at disease onset affects their clinical phenotype. We here investigate the relationship between age at disease onset and symptoms in a large cohort of SSc patients (lcSSc, dcSSc and SSc-overlap syndromes).MethodsClinical data of the registry of the German Network for Systemic Scleroderma including 3281 patients were evaluated and subdivided into three age groups at disease onset (60 years).ResultsAmong all SSc patients, 24.5% developed their first non-Raynaud phenomenon symptoms at the age 60 years), except for gastrointestinal and musculoskeletal involvement. No significant difference was found for the use of corticosteroids. However, significantly, fewer patients older than 60 years received immunosuppressive treatment.ConclusionIn this large registry, ∼25% of patients developed SSc at an age above 60 years with an increased frequency of lcSSc. In this age group, an onset of internal organ involvement was significantly accelerated across all three subsets. These findings suggest that, in the elderly cohort, more frequent follow-up examinations are required for an earlier detection of organ complications.

IntroductionSeveral risk factors for severe COVID-19 specific for patients with inflammatory rheumatic and musculoskeletal diseases (RMDs) have been identified so far. Evidence regarding the influence of different RMD treatments on outcomes of SARS-CoV-2 infection is still poor.MethodsData from the German COVID-19-RMD registry collected between 30 March 2020 and 9 April 2021 were analysed. Ordinal outcome of COVID-19 severity was defined: (1) not hospitalised, (2) hospitalised/not invasively ventilated and (3) invasively ventilated/deceased. Independent associations between demographic and disease features and outcome of COVID-19 were estimated by multivariable ordinal logistic regression using proportional odds model.Results2274 patients were included. 83 (3.6%) patients died. Age, male sex, cardiovascular disease, hypertension, chronic lung diseases and chronic kidney disease were independently associated with worse outcome of SARS-CoV-2 infection. Compared with rheumatoid arthritis, patients with psoriatic arthritis showed a better outcome. Disease activity and glucocorticoids were associated with worse outcome. Compared with methotrexate (MTX), TNF inhibitors (TNFi) showed a significant association with better outcome of SARS-CoV-2 infection (OR 0.6, 95% CI0.4 to 0.9). Immunosuppressants (mycophenolate mofetil, azathioprine, cyclophosphamide and ciclosporin) (OR 2.2, 95% CI 1.3 to 3.9), Janus kinase inhibitor (JAKi) (OR 1.8, 95% CI 1.1 to 2.7) and rituximab (OR 5.4, 95% CI 3.3 to 8.8) were independently associated with worse outcome.ConclusionGeneral risk factors for severity of COVID-19 play a similar role in patients with RMDs as in the normal population. Influence of disease activity on COVID-19 outcome is of great importance as patients with high disease activity—even without glucocorticoids—have a worse outcome. Patients on TNFi show a better outcome of SARS-CoV-2 infection than patients on MTX. Immunosuppressants, rituximab and JAKi are associated with more severe course.

Objectives To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-month lockdown in Germany. Methods From 16th March until 15th June 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. Results The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients ( Conclusion The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behaviour with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendations of the German Society of Rheumatology were well received, supporting the well-established physician–patient relationship in times of a crisis.

IntroductionWhether patients with inflammatory rheumatic and musculoskeletal diseases (RMD) are at higher risk to develop severe courses of COVID-19 has not been fully elucidated. Aim of this analysis was to describe patients with RMD according to their COVID-19 severity and to identify risk factors for hospitalisation.MethodsPatients with RMD with PCR confirmed SARS-CoV-2 infection reported to the German COVID-19 registry from 30 March to 1 November 2020 were evaluated. Multivariable logistic regression was used to estimate ORs for hospitalisation due to COVID-19.ResultsData from 468 patients with RMD with SARS-CoV-2 infection were reported. Most frequent diagnosis was rheumatoid arthritis, RA (48%). 29% of the patients were hospitalised, 5.5% needed ventilation. 19 patients died. Multivariable analysis showed that age >65 years (OR 2.24; 95% CI 1.12 to 4.47), but even more>75 years (OR 3.94; 95% CI 1.86 to 8.32), cardiovascular disease (CVD; OR 3.36; 95% CI 1.5 to 7.55), interstitial lung disease/chronic obstructive pulmonary disease (ILD/COPD) (OR 2.79; 95% CI 1.2 to 6.49), chronic kidney disease (OR 2.96; 95% CI 1.16 to 7.5), moderate/high RMD disease activity (OR 1.96; 95% CI 1.02 to 3.76) and treatment with glucocorticoids (GCs) in dosages >5 mg/day (OR 3.67; 95% CI 1.49 to 9.05) were associated with higher odds of hospitalisation. Spondyloarthritis patients showed a smaller risk of hospitalisation compared with RA (OR 0.46; 95% CI 0.23 to 0.91).ConclusionAge was a major risk factor for hospitalisation as well as comorbidities such as CVD, ILD/COPD, chronic kidney disease and current or prior treatment with GCs. Moderate to high RMD disease activity was also an independent risk factor for hospitalisation, underlining the importance of continuing adequate RMD treatment during the pandemic.

ObjectivesPatients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany.MethodsUsing an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters—for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection—are documented.ResultsUntil 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course.ConclusionsIn a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.

Background:Patients with inflammatory rheumatic diseases (IRD) and infection with SARS-CoV-2 may be at risk to develop a severe course of COVID-19. To gather knowledge about SARS-CoV-2 infections in IRD patients, a national registry was established to elucidate IRD specific profiles of COVID-19.Objectives:To identify risk factors for hospitalisation.Methods:Patients from the German registry on SARS-CoV-2 infection in IRD were analysed. Patients are enrolled with a pre-existing IRD and a positive lab-result for a SARS-CoV-2 infection. The main outcome parameter was hospitalisation versus non-hospitalisation. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Covariates included in the model were age group, gender, key comorbidities (cardiovascular, lung diseases, chronic renal insufficiency), prior and/or current use of glucocorticosteroids (GC) or NSAIDs and remission.Results:Until May 17th, 2020, data from 192 IRD patients with SARS-CoV-2 infection were reported (67 males; 124 females; 1 diverse). 64 patients were hospitalised, 21 patients were ventilated non-invasively/invasively and 15 patients died.Baseline characteristics are shown in table 1, stratified into the patient groups non-hospitalisation, hospitalisation without ventilation, and hospitalisation with ventilation. Non-hospitalised patients were younger, had less comorbidities and were less often treated with GC. In the group of hospitalised patients compared to non-hospitalised patients more patients were male (42% vs 32% male) with an even higher proportion in the ventilated patient group (57% male).In the multivariable logistic regression model, age>65 years (OR 5.1; 95%CI 2.3-11.4), cardiovascular comorbidity (OR 2.3; 95%CI 1.0-5.0), and prior and/or current treatment with GC (OR 2.6; 95%CI 1.2-5.4) were independently associated with hospitalisation.Parameter, N (%)Non-hospitalisation128 (66.7)Hosp. without ventilation42 (22.4)Hosp. with ventilation21 (10.9)Age [years], mean (SD)53.8 (13.4)65.2 (15.5)69.7 (9.9)Female87 (68.5)28 (65.1)9 (42.9)RA60 (46.9)24 (55.8)12 (57.1)Psoriasis23 (18)3 (7)3 (14.3)Axial spondyloarthritis14 (10.9)2 (4.7)0Lupus7 (5.5)1 (2.3)0Remission of IRD67 (52.3)23 (53.5)4 (19)Number of comorbidities, mean (SD)1 (1.2)1.8 (1.4)2.4 (1.5)Cardiovascular disease42 (32.8)25 (58.1)16 (76.2)Pulmonary disease16 (12.5)8 (18.6)8 (38.1)Chronic renal insufficiency5 (3.9)7 (16.3)4 (19)Cancer2 (1.6)4 (9.3)2 (9.5)Obesity (BMI>30)23 (18)5 (11.6)3 (14.3)Diabetes3 (2.3)7 (16.3)4 (19)Other comorbidities20 (15.6)9 (20.9)6 (28.6)csDMARD (without HCQ)59 (46.1)25 (58.1)8 (38.1)HCQ13 (10.2)1 (2.3)2 (9.5)bDMARD48 (37.5)15 (34.9)8 (38.1)tsDMARD5 (3.9)1 (2.3)1 (4.8)Glucocorticosteroids47 (37)29 (67.4)13 (61.9)NSAIDs21 (16.4)5 (11.6)1 (4.8)Conclusion:As has been described for COVID-19 in general, also in IRD male gender may be associated with a more severe course of the infection as the descriptive analysis of data shows. Risk factors for SARS-CoV-2 infection-dependent hospitalisation in IRD patients include age (>65 years), cardiovascular comorbidities, and prior and/or current treatment with GC.Disclosure of Interests:Anne Regierer Speakers bureau: Novartis, Celgene, Janssen-Cilag, Rebecca Hasseli Grant/research support from: Pfizer, Consultant of: Pfizer, Gilead, Novartis, Celgene, Abbvie, Medac, Bimba Hoyer: None declared, Andreas Krause: None declared, Hanns-Martin Lorenz Grant/research support from: Consultancy and/or speaker fees and/or travel reimbursements: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly. Scientific support and/or educational seminars and/or clinical studies: Abbvie, MSD, BMS, Pfizer, Celgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, Astra-Zeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, Thermo Fisher., Consultant of: see above, Alexander Pfeil Grant/research support from: This study Investigator Initiated Study “Automatic assessment of joint space narrowing in rheumatoid arthritis based on the Post-hoc analysis” (number: IIS-2016-110818) is a part of the of the Investigator Initiated Study “The quantification of inflammatory related periarticular bone loss in certolizumab pegol treated patients with rheumatoid arthritis” (number: IIS-2014-101458) which is supported by UCB Pharma GmbH, Monheim, Germany., Jutta Richter Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Tim Schmeiser Speakers bureau: Actelion, UCB, Pfizer, Christof Specker Consultant of: Abbvie, Boehringer Ingelheim, Chugai, Lilly, Novartis, Sobi, UCB, Celgene, Janssen-Cilag, MSD, Pfizer, Roche, UCB, Toshiba, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Reinhard Voll: None declared, Hendrik Schulze-Koops: None declared, Ulf Müller-Ladner Speakers bureau: Biogen

The current COVID-19 pandemic inherits an unprecedented challenge for the treating rheumatologists. On the one hand, antirheumatic drugs can increase the risk of infection and potentially deteriorate the course of an infection. On the other hand, an active inflammatory rheumatic disease can also increase the risk for an infection. In the recommendations of the German Society for Rheumatology (www.dgrh.de), it is recommended that our patients continue the antirheumatic therapy to maintain remission or low state of activity despite the pandemic. In this study, patients with inflammatory rheumatic disease were asked in the first weeks of the pandemic on their opinion of their immunomodulating therapy. The result shows that over 90% of the patients followed the recommendation of the rheumatologist to continue the antirheumatic therapy, and only a small percentage of the patients terminated the therapy on their own. This result was independent of the individual anti-rheumatic therapy. Taken together, the results of this study illustrate not only the trustful patient-physician partnership in a threatening situation but also the high impact of state-of-the art recommendations by the respective scientific society.

ObjectivesThe aim of this study was to adapt the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into six European cultures and validate it as a common measure of quality of life in systemic sclerosis (SSc).MethodsThis was a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross-sectional study. A forward–backward translation process was used to adapt the English SScQoL into target languages. SScQoL was completed by patients with SSc, then data were validated against the Rasch model. To correct local response dependency, items were grouped into the following subscales: function, emotion, sleep, social and pain and reanalysed for fit to the model, unidimensionality and cross-cultural equivalence.ResultsThe adaptation of the SScQoL was seamless in all countries except Germany. Cross-cultural validation included 1080 patients with a mean age 58.0 years (SD 13.9) and 87% were women. Local dependency was evident in individual country data. Grouping items into testlets corrected the local dependency in most country specific data. Fit to the model, reliability and unidimensionality was achieved in six-country data after cross-cultural adjustment for Italy in the social subscale. The SScQoL was then calibrated into an interval level scale.ConclusionThe individual SScQoL items have translated well into five languages and overall, the scale maintained its construct validity, working well as a five-subscale questionnaire. Measures of quality of life in SSc can be directly compared across five countries (France, Poland Spain, Sweden and UK). Data from Italy are also comparable with the other five countries although require an adjustment.

Background:Patients with rheumatic and musculoskeletal diseases (RMD) might have an increased risk for infection due to their immunomodulatory treatment, secondary to their disease and comorbidities. Recent studies suggest a decreased risk of severe COVID-19 in RMD-patients treated with biologics.Objectives:The aim of this study was to assess courses of RMD patients treated with TNF-inhibitors (TNF-I) included in the German COVID-19 registry.Methods:In the German physician-reported COVID-19-RMD registry, patients with an RMD and confirmed SARS-CoV-2-infection were documented (data entered between March 30, 2020 and January 30, 2021). We analysed TNF-I treated patients, their course and outcome of the infection. Data were compared to RMD-patients treated with other immunomodulatory drugs (OID) than TNF-I.Results:A total of 269 patients were treated with a TNF-I (57% female) compared to 874 patients who were treated with OID (68% female). Median age was 52 years (range: 19-87) in the TNF-I-group versus 58 years (range: 18-91) in the OID-group. Rheumatoid arthritis was the most common diagnosis (38% in TNF-I-group vs. 52% in the OID-group), followed by ankylosing spondylitis (32% vs. 6%), psoriatic arthritis (22% vs. 11%) and other RMD (9% vs. 31%). Adalimumab (35%) and etanercept (35%) were the most frequently used TNF-I (tab. 1). Glucocorticoids (GC) were used in 22% of TNF-I-treated patients and in 42% of the OID-group.Under TNF-I, stable disease was reported prior to the SARS-CoV-2-infection in 53% of the patients (OID-group: 47%), followed by low disease activity in 35% (OID: 34%), moderate disease activity in 6% (OID: 12%) and high disease activity in 4% (OID: 3%). Most frequent comorbidities were arterial hypertension (29% under TNF-I vs. 35% under OID), diabetes (8% vs. 11%) and cardiovascular diseases (7% vs. 12%).The most common reported COVID-19 symptoms were dry cough (57% vs. 55%), fever (53% vs. 61%) and fatigue (50% vs. 49%). Hospitalization due to SARS-CoV infection was required in only 12% of the TNF-I-treated cases vs. in 29% in the OID-group. Oxygen treatment was necessary in 5% of the patients under TNF-I compared to 22% under OID and invasive ventilation in 2% in the TNF-I-group compared to 6% under OID. Most notably, no fatal courses of COVID-19 were reported among the 269 RMD-patients treated with TNF-I versus 49 deaths in the 874 cases (5.6%) treated with OID. Focussing on the hospitalizated TNF-I patients, the rate of concomitant GC use (pConclusion:High or moderate RMD-disease activity is an important factor associated with severity of COVID-19 including mortality. In this large cohort RMD patients treated with TNF-I show a low hospitalisation rate and no fatal course. This is reassuring for patients and treating rheumatologists to use TNF-I to control RMD disease activity. The use of glucocorticoids and high disease activity seem to counteract possible protective effects of TNF-I.Table 1.TNF inhibition (269)Other immunomodulation (874)Total patientsRate (%)Total patientsRate (%)Disease activitystable1415340847low933529934Moderate15610812High104293Comorbiditiescardiovascular diseases18710412arterial hypertension772930335bronchial asthma124657COPD/interstitial lung disease1148610chronic renal failure93779Osteoporosis135678Diabetes2289211COVID-19 related symptomsFever1425347855dry cough1525753061Expectoration3112839muscular pain973628032Fatigue1355042449Headache1013823727shortness of breath491824528no symptoms239566COVID-19 outcomeOutpatients2378861971Inpatients321225529need of oxygen treatment18718922invasive ventilation52496fatal course00496TNF inhibitorsAdalimumab9535Infliximab239Certolizumab3312Golimumab249Etanercept9435GC and disease activity in TNF-I treated patientsTNF-I inpatients treated with GC18/3256p< 0.001TNF-I outpatients treated with GC42/23718TNF-I inpatients with high disease activity4/3213TNF-I outpatients with high disease activity6/2376p= 0.005Acknowledgements:The authors would like to thank all physicians and personnel involved in the documentation of the cases in our registry.Disclosure of Interests:None declared

Background:Tocilizumab (TCZ) showed trends for improving skin fibrosis and prevented progression of lung fibrosis in patients with systemic sclerosis (SSc) in placebo-controlled randomised clinical trials (RCTs). However, safety and effectiveness of TCZ beyond these selected and enriched clinical trial populations in SSc is still unknown.Objectives:To assess safety and effectiveness of TCZ treatment compared to standard of care in SSc patients from the large, multicentre, observational, real-life EUSTAR network/database using propensity score matching.Methods:SSc patients from the EUSTAR network/database, who fulfilled the ACR/EULAR 2013 classification criteria, with a baseline and a follow-up visit at 12±3 months, receiving TCZ or standard of care (controls), were selected. The following variables were used for the propensity score matching (1:1): age at diagnosis, gender, disease subtype, baseline modified Rodnan skin score (mRSS), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), co-therapy with immunosuppressives, disease duration, and year of treatment. Primary endpoints were mRSS and FVC at 12±3 months follow-up compared between the groups, using paired t-tests. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months follow-up according to standard definitions (1,2). Sensitivity analyses assessed pre-processing decisions (selection of most recent vs. random observation for control patients with multiple suitable time intervals), as well as the matching method (optimal vs. exact matching). Missing values were addressed with 100-fold multiple imputation using chained equations. Safety data were analysed in all patients. The study including the statistical analysis plan was pre-registered at www.drks.de (DRKS-ID: DRKS00015537).Results:We identified 93 SSc patients treated with TCZ and 2370 SSc patients with standard of care who fulfilled the inclusion criteria. Forty nine (57.7%) of the TCZ treated patients were diffuse, eight patients were not classified, disease duration was (mean±SD) 6.35±5.40 years, their baseline mRSS was 15.05±10.85, and 76 (81.7%) received immunosuppressive therapy in addition to TCZ.Through multiple imputation and propensity score matching, 100 imputed sets of 93 pairs of TCZ/controls were generated. Comparison between groups showed consistent effects of TCZ across all pre-defined primary and secondary endpoints: mRSS was lower in the TCZ group (mean difference (95% confidence interval (CI)) -1.8 (-4.79 to 1.19), p=0.24, Figure 1A). Similarly, FVC % predicted was higher in the TCZ group mean difference (2.25, 95% CI -4.57 to 9.06), p=0.51, Figure 1B). Considering secondary endpoints, the percentage of skin progressors as well as lung progressors at follow up was lower in the TCZ group (odds ratio OR 0.67 (95% CI 0.07 to 6.41), p=0.74 and OR 0.53 (95% CI 0.16 to 1.7); p=0.2, respectively. Consistently, the percentage of regressors for skin (OR 1.6 (95% CI 0.56 to 4.54), p=0.38) and for lung (OR 1.74 (95% CI 0.66 to 4.58), p=0.26) was higher in TCZ. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.Conclusion:In this large, observational, controlled, real-life EUSTAR study, effectiveness of TCZ did not reach statistical significance compared to standard of care treatment but showed consistent positive effects of TCZ on skin and lung fibrosis across all pre-defined primary and secondary endpoints confirming data from recent RCTs.References:[1]Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis. Ann Rheum Dis 2016:1743-8.[2]Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis 2021:219-227.Disclosure of Interests:Simon Kuster: None declared, Suzana Jordan: None declared, Muriel Daniele Elhai: None declared, Ulrike Held: None declared, Klaus Steigmiller: None declared, Cosimo Bruni: None declared, Florenzo Iannone: None declared, Serena Vettori: None declared, Elise Siegert: None declared, Simona Rednic: None declared, Veronica Codullo: None declared, Paolo Airò Consultant of: Dr. Airo’ reports personal fees (consultancies) from Bristol Myers Squibb, Bohringer Ingelheim, non-financial support from CSL Behring, SOBI, Janssen, Roche, Sanofi, Pfizer, Yolanda Braun-Moscovici: None declared, Nicolas Hunzelmann: None declared, Maria Joao Salvador: None declared, Valeria Riccieri: None declared, Ana Maria Gheorghiu: None declared, Juan Jose Alegre Sancho: None declared, Katarzyna Romanowska-Prochnicka: None declared, Ivan Castellví: None declared, Ina Koetter: None declared, Marie-Elise Truchetet Consultant of: Marie-Elise Truchetet has had consultancy relationships and/or has received research funding from Boehringer Ingelheim, Genentech/Roche, and Sanofi in the area of potential treatments of scleroderma and its complications., Grant/research support from: Marie-Elise Truchetet has had consultancy relationships and/or has received research funding from Boehringer Ingelheim, Genentech/Roche, and Sanofi in the area of potential treatments of scleroderma and its complications., Francisco J López-Longo: None declared, Pavel Novikov: None declared, Alessandro Giollo: None declared, Yuichiro Shirai: None declared, Laura Belloli: None declared, Elisabetta Zanatta: None declared, Eric Hachulla: None declared, Vanessa Smith: None declared, Christopher Denton: None declared, Ruxandra Ionescu: None declared, Tim Schmeiser: None declared, Jörg H.W. Distler: None declared, Armando Gabrielli: None declared, Anna-Maria Hoffmann-Vold Consultant of: AMHV has received research funding and/or consulting fees and/or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Grant/research support from: AMHV has received research funding and/or consulting fees and/or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape. Masataka Kuwana: None declared, Yannick Allanore: None declared, Oliver Distler Speakers bureau: Oliver Distler 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: Oliver Distler 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: The study was partially supported by a grant from Roche. Roche was not involved in analysis or interpretation of the results.

Background SSc is a heterogeneous multisystem connective tissue disease. The majority of patients (pts) develop initial clinical symptoms between the ages of 30-50 years (yrs). It is not yet known whether the age of onset has an influence on the development of a distinct clinical phenotype. Objectives Investigating the relationship between age at disease onset and the development of clinical characteristics using data of the German Network for Systemic Scleroderma. Methods We evaluated 2928 patient data, subdivided them into 3 age groups at disease onset ( 60 years) and correlated the age at disease onset with specific clinical characteristics. Results Overall, 24% of pts developed first non-RP symptoms at the age of 60yrs developed significantly (p Conclusion In this registry, approximately one quarter of pts developed SSc at an age above 60yrs, predominantly having a lcSSc subtype. Although these pts have been diagnosed with the mild form of SSc, pts with a lcSSc subtype at a higher age (>60yrs) had more frequent a PH and showed a more rapid disease progression than the youngest pts. These findings may have an important influence on recommendations on diagnosis, frequency of follow-ups and therapy of SSc in different age groups. Disclosure of Interests Pia Moinzadeh Speakers bureau: Actelion, Kathrin Kuhr: None declared, Ulf Muller-Ladner Grant/research support from: Projekt supported by an unrestricted educational grant from Celgene GmbH., Elise Siegert Shareholder of: Astra Zeneca, Grant/research support from: Actelion, Consultant for: AEC Partners, Speakers bureau: Actelion, Norsk, Jorg Henes: None declared, Gabriela Riemekasten Consultant for: Chugai, F. Hoffmann-La Roche, Speakers bureau: Chugai, F. Hoffmann-La Roche, Norbert Blank Grant/research support from: SOBI and Novartis, Speakers bureau: Novartis and SOBI, Marc Schmalzing Grant/research support from: Pfizer, Chugai, MSD, Janssen-Cilag, BMS, Celgene, UCB, Consultant for: Abbvie, Chugai, Genzyme, Hexal/Sandoz, MSD, Novartis, Roche, Sanofi Pasteur, Speakers bureau: Actelion, Baxalta/Shire, BMS, Celgene, Chugai, Janssen-Cilag, MSD, Novartis, Pfizer, Roche, UCB, Ina Koetter: None declared, Claudia Guenther Grant/research support from: Pfizer, Novartis, Employee of: 20 years ago, Novartis, Speakers bureau: Celtis, Tim Schmeiser Speakers bureau: Actelion, UCB, Pfizer, Gabriele Zeidler Grant/research support from: MSD Sharp & Dohme GmbH Actelion Pharmaceuticals Deutschland GmbH Roche Pharma AG AbbVie Deutschland GmbH Co. KG Pfizer Pharma GmbH Lilly Deutschland GmbH Celgene GmbH Bristol–Myers Squibb UCB Pharma GmbH/UCB GmbH Speakers bureau: MSD Sharp & Dohme GmbH Actelion Pharmaceuticals Deutschland GmbH Roche Pharma AG AbbVie Deutschland GmbH Co. KG Pfizer Pharma GmbH Lilly Deutschland GmbH Celgene GmbH Bristol–Myers Squibb UCB Pharma GmbH/UCB GmbH Disclosure of Interests Alexander Kreuter Speakers bureau: Actelion Pharma, MSD, AbbVie, InfektioPharm, Margitta Worm: None declared, Laura Susok: None declared, Aaron Juche: None declared, Christiane Pfeiffer: None declared, Cord Sunderkoetter: None declared, Donja Homayoon: None declared, Nicolas Hunzelmann Speakers bureau: Boehringer Ingelheim, Actelion, Pfizer, Roche

Background Pulmonary involvement is the leading cause of death in SSc and can manifest as interstitial lung disease (ILD), pulmonary hypertension (PAH) or a combination (ILD-PH). Aim of this analysis was to determine prevalence, clinical characteristics and outcomes of different forms within the German SSc Network. Objectives Methods SSc patients were analyzed for pulmonary involvement, clinical characteristics and outcome. Results There were 3699 pts in 42 centers with a mean follow up time of 34.4±12.6 months. At baseline, ILD was frequent (29.5%), while ILD-PH and PAH had lower prevalences (7.5%, 6.1%). At the end of follow up, 32% of SSc pts had ILD, 13% ILD-PH and 7% PAH. ILD and ILD-PH were more frequent in the diffuse form (47%, 12%), while PAH did not differ between subforms. Significant differences in baseline characteristics between PAH vs. ILD-PH vs. ILD were found for age (62, 59, 54 years), sex (males: 15%, 22%, 24%) and smoking prevalence (non-smokers 49%, 63%, 57%). Mean DLCO and FVC were 56%/93% for PAH, 49%/78% for ILD-PH and 56%/81% for ILD. Significant decreases for DLCO (≥15%) and FVC (≥10%) were found in 45%/26% in PAH, 45%/26% for ILD-PH and 36%/16% in ILD. All-cause mortality was 8.1% for the total cohort and differed significantly between patients without pulmonary involvement (4%), ILD (7.8%), PAH (14.2%), and ILD-PH (21%, p Conclusion ILD is the most prevalent pulmonary involvement in SSc, while PH-ILD is associated with the most detrimental survival. Significant differences in baseline characteristics of types of pulmonary SSc involvement may help to identify patients at risk in the future. Disclosure of Interests: Michael Kreuter Grant/research support from: Boehringer Ingelheim, Roche Pharma, Consultant for: Boehringer Ingelheim, Roche Pharma, Speakers bureau: Boehringer Ingelheim, Roche Pharma, Francesco Bonella Consultant for: Boehringer Ingelheim, Roche Pharma, Speakers bureau: Boehringer Ingelheim, Roche Pharma, Ulf Muller-Ladner Grant/research support from: Projekt supported by an unrestricted educational grant from Celgene GmbH., Elise Siegert Shareholder of: Astra Zeneca, Grant/research support from: Actelion, Consultant for: AEC Partners, Speakers bureau: Actelion, Norsk, Jorg Henes: None declared, Gabriela Riemekasten Consultant for: Chugai, F. Hoffmann-La Roche, Speakers bureau: Chugai, F. Hoffmann-La Roche, Norbert Blank Grant/research support from: SOBI and Novartis, Speakers bureau: Novartis and SOBI, Marc Schmalzing Grant/research support from: Pfizer, Chugai, MSD, Janssen-Cilag, BMS, Celgene, UCB, Consultant for: Abbvie, Chugai, Genzyme, Hexal/Sandoz, MSD, Novartis, Roche, Sanofi Pasteur, Speakers bureau: Actelion, Baxalta/Shire, BMS, Celgene, Chugai, Janssen-Cilag, MSD, Novartis, Pfizer, Roche, UCB, Ina Koetter: None declared, Claudia Guenther Grant/research support from: Pfizer, Novartis, Employee of: 20 years ago, Novartis, Speakers bureau: Celtis, Tim Schmeiser Speakers bureau: Actelion, UCB, Pfizer, Gabriele Zeidler Grant/research support from: MSD Sharp & Dohme GmbH Actelion Pharmaceuticals Deutschland GmbH Roche Pharma AG AbbVie Deutschland GmbH Co. KG Pfizer Pharma GmbH Lilly Deutschland GmbH Celgene GmbH Bristol-Myers Squibb UCB Pharma GmbH/UCB GmbH, Speakers bureau: MSD Sharp & Dohme GmbH Actelion Pharmaceuticals Deutschland GmbH Roche Pharma AG AbbVie Deutschland GmbH Co. KG Pfizer Pharma GmbH Lilly Deutschland GmbH Celgene GmbH Bristol-Myers Squibb UCB Pharma GmbH/UCB GmbH, Alexander Kreuter Speakers bureau: Actelion Pharma, MSD, AbbVie, InfektioPharm, Margitta Worm: None declared, Laura Susok: None declared, Aaron Juche: None declared, Christiane Pfeiffer: None declared, Cord Sunderkoetter: None declared, Donja Homayoon: None declared, Kathrin Kuhr: None declared, Hanns-Martin Lorenz: None declared, Pia Moinzadeh Speakers bureau: Actelion, Nicolas Hunzelmann Speakers bureau: Boehringer Ingelheim, Actelion, Pfizer, Roche

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

Background:Elderly rheumatoid arthritis (RA) patients are generally at increased risk of serious infections (SI). At the same time, treatment with bDMARDs has been associated with a higher SI risk than treatment with csDMARDs (1). However, long-term use of bDMARDs did not increase the risk of SI in a small group of elderly patients over 65 (2). The extent to which elderly patients are exposed to a higher SI risk when treated with JAK inhibitors (JAKi) is an open question.Objectives:To assess the effects of bDMARDs and specifically JAKi on the risk of SI in elderly patients with RA.Methods:The German register RABBIT is a prospective, longitudinally followed cohort of RA patients enrolled with a new start of a DMARD after at least one csDMARD failure. This analysis comprises patients over 70 years of age who were enrolled between 01/2007 and 04/2020 and had at least one follow-up.Results:Of 13,491 patients followed-up in RABBIT, 2274 with an age > 70 years were included in the analysis. 626 SI were observed in 425 of these patients. Baseline characteristics at start of the respective DMARD are shown in Table 1. In most characteristics, patients on JAKi were more comparable to patients under bDMARDs than to those on csDMARDs. JAKi patients received glucocorticoids (GC) less frequently than patients on other treatments. The HR for SI was lower than 1 in patients receiving bDMARDs or JAKi compared to csDMARDs, but without statistical significance (Figure 1). GC use (HR 1.6, 95% CI: 1.2 – 2.2 for ≤ 10 mg/d), higher DAS28-ESR values (HR 1.1, 95% CI: 1.0 – 1.2 per 1 point increase), COPD or pulmonary fibrosis (HR 1. 8, 95% CI: 1.3 – 2.4), chronic kidney disease (HR 1.5, 95% CI: 1.2 – 1.9) and diabetes mellitus (HR 1.3, 95% CI: 1.0 – 1.7) were associated with an increased risk of SI. Better physical capacity was associated with a decreased risk of SI (HR 0.9, 95% CI: 0.88 – 0.98 for a 10 point increase).Table 1.Patient characteristics by treatment at baselineParametercsDMARDsTNFiRTXABAIL-6iJAKiN=758N=840N=209N=147N=212N=108Age (years)75.9 (3.9)75.5 (3.6)74.8 (3.6)76.1 (3.9)75.9 (3.7)76.7 (3.7)Male sex184 (24.3)220 (26.2)50 (23.9)36 (24.5)46 (21.7)28 (25.9)Ever smoker249 (32.8)287 (34.2)77 (36.8)50 (34)73 (34.4)39 (36.1)Disease duration (years)7.9 (8.8)12.3 (11.4)17 (11.1)12.8 (10)13.8 (11.7)11.9 (10.9)Seropositivity487 (64.3)671 (79.9)201 (96.2)126 (85.4)182 (85.8)79 (73.5)Number of previous DMARDs1.4 (0.7)2.5 (1.3)4.2 (1.8)3.6 (1.9)3.3 (1.8)2.6 (1.5)DAS28-ESR4.6 (1.2)5.1 (1.2)5.4 (1.3)5.3 (1.3)5.3 (1.3)5 (1.2)Proportion of full physical function64.8 (23.1)57.1 (23.6)50.4 (23.7)52.9 (23.5)55.3 (24.1)55.2 (23.7)Number of comorbidities3.1 (2.5)3.8 (2.6)4.2 (2.6)4.6 (2.9)3.6 (2.4)3.8 (2.2)No comorbidity52 (6.9)29 (3.5)4 (1.9)4 (2.7)9 (4.2)5 (4.6)Three and more comorbidities385 (50.8)528 (62.9)147 (70.3)107 (72.8)131 (61.8)76 (70.4)COPD or pulmonary fibrosis69 (9.1)89 (10.6)29 (13.9)26 (17.7)12 (5.7)11 (10.2)Chronic kidney disease94 (12.4)151 (18)28 (13.4)21 (14.3)39 (18.4)22 (20.4)Diabetes mellitus151 (19.9)172 (20.5)31 (14.8)23 (15.6)42 (19.8)25 (23.1)GCs (last 6 months)347 (45.8)526 (62.6)143 (68.8)82 (56.2)127 (59.9)44 (40.7)GCs (447 (58.9)384 (45.7)101 (48.2)88 (60)118 (55.8)72 (66.7)GCs (5-9mg)252 (33.3)375 (44.6)81 (38.7)43 (29)72 (34.2)27 (25.1)GCs (>=10mg)59 (7.8)82 (9.8)274 (13.1)16 (11)21 (10)9 (8.2)Results are presented as mean ± SD for continuous variables and number (percentage) for discrete variables.Figure 1.Hazard ratios for serious infections with 95% confidence intervalsConclusion:Treatment with JAKi as well as treatment with bDMARDs was not associated with an increased risk of SI in elderly patients above 70 years of age. Key comorbidities such as diabetes mellitus, chronic pulmonary and kidney diseases were associated with increased risk, as was concomitant GC use and higher disease activity.References:[1] Listing J et al., Rheumatology 2013; 52 (1): 53-61.[2] Kawashima H. et al., Rheum. Intern. 2017; 37: 369-376.Acknowledgements:RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Celltrion, Fresenius-Kabi, Gilead, Hexal, Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, UCB, and Viatris.Disclosure of Interests:None declared

Background:Gastroesophageal reflux disease (GERD) occurs frequently in patients with systemic sclerosis (SSc) and SSc-associated interstitial lung disease (SSc-ILD). PPI use has to been shown to improve survival in patients with idiopathic pulmonary fibrosis, whereas to date there are no data on the use of PPI in SSc-ILD.Objectives:This study was aimed to assess whether use of PPI is associated with progression of SSc-ILD and survival.Methods:We retrospectively analysed 1931 patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan–Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with vs. without GERD (SSc and SSc-ILD), and PPI vs. no PPI use (SSc-ILD only). Progression was defined as a decrease in either % predicted forced vital capacity ≥10% or single-breath diffusing capacity for carbon monoxide ≥15%, or death.Results:GERD was not associated with decreased OS or PFS in patients with either SSc or SSc-ILD. In patients with SSc-ILD, PPI use was associated with improved OS vs. no PPI use after 1 year (98.4% [95% confidence interval: 97.6–99.3]; n=760 vs. 90.8% [87.9–93.8]; n=290) and after 5 years (91.4% [89.2–93.8]; n=357 vs. 70.9% [65.2–77.1]; n=106; pConclusion:GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD; however, controlled, prospective trials are needed to confirm this finding.Disclosure of Interests:Michael Kreuter Speakers bureau: Boehringer, Consultant of: Boehringer, Grant/research support from: Boehringer, Francesco Bonella Speakers bureau: Boehringer, Roche, GSK, Consultant of: Boehringer, Roche, GSK, Grant/research support from: Boehringer, Kuhr Kathrin: None declared, Jörg Henes Speakers bureau: Abbvie, Boehringer, Chugai, Roche, Janssen, Novartis, SOBI, Pfizer and UCB, Consultant of: Boehringer, Celgene, Chugai, Roche, Janssen, Novartis, SOBI, Grant/research support from: Chugai, Roche, Janssen, Novartis, SOBI, Pfizer, Elise Siegert: None declared, Gabriela Riemekasten Speakers bureau: Novartis, Janssen, Roche, GSK, Boehringer, Consultant of: Janssen, Actelion, Boehringer, Norbert Blank Consultant of: Sobi, Novartis, Roche, UCB, MSD, Pfizer, Actelion, Abbvie, Boehringer, Grant/research support from: Novartis, Sobi, Christiane Pfeiffer: None declared, Ulf Müller-Ladner: None declared, Alexander Kreuter Speakers bureau: MSD, Boehringer, InfectoPharm, Paid instructor for: MSD, PETER KORSTEN Consultant of: Glaxo, Abbvie, Pfizer, BMS, Chugai, Sanofi, Lilly, Boehringer, Novartis, Grant/research support from: Glaxo, Aaron Juche: None declared, Marc Schmalzing Speakers bureau: Chugai Roche, Boehringer, Celgene, Medac, UCB, Paid instructor for: Novartis, Abbvie, Astra Zeneca, Chugai Roche, Janssen, Consultant of: Chugai Roche, Hexal Sandoz, Gilead, Abbvie, Janssen, Boehringer, Margitta Worm Speakers bureau: Boehringer, Ilona Jandova Speakers bureau: Boehringer, Novartis, Abbvie, Laura Susok Speakers bureau: MSD, Novartis, BMS, Sunpharma, Consultant of: MSD, Tim Schmeiser Consultant of: Abbvie, Boehringer, Novartis, UCB, Claudia Guenther Paid instructor for: Advisory Board Boehringer January 2020, Employee of: Novartis 2002-2005, Gernot Keyszer Consultant of: Boehringer, Jan Ehrchen Speakers bureau: Boehringer, Janssen, Chugai, Sobi, Employee of: Pfizer, Actelion (now Janssen), Andreas Ramming Speakers bureau: Boehringer, Gilead, Janssen, Pfizer, Roche, Consultant of: Boehringer, Pfizer, Grant/research support from: Novartis, Pfizer, Ina Kötter Speakers bureau: several companies, Consultant of: several companies, Grant/research support from: several companies, Hanns-Martin Lorenz Speakers bureau: Abbvie, Astra Zeneca, Actelion, Alexion Amgen, Bayer Vital, Baxter, Biogen, Boehringer, BMS, Celgene, Fresenius, Genzyme, GSK, Gilead, Hexal, Janssen, Lilly, Medac, MSD, Mundipharm, Mylan, Novartis, Octapharm, Pfizer, Roche Chugai, Sandoz, Sanofi, Shire SOBI, Thermo Fischer, UCB, Grant/research support from: basic research studies: Pfizer, Novartis, Abbvie, Gilead, Lilly, MSD, Roche Chugai, Pia Moinzadeh Speakers bureau: Boehringer, Actelion, Grant/research support from: Actelion, Nicolas Hunzelmann Speakers bureau: Boehringer Janssen, Roche, Sanofi, Consultant of: Boehringer

To determine the type and frequency of physical therapy (PT) prescribed by physicians for patients in the registry of the German Network for Systemic Sclerosis.The data for 4,252 patients were analyzed using descriptive statistics, chi-square tests, and odds ratios (ORs).Overall, 37.4% of patients (1,590 of 4,252) received PT at the end of a yearly follow-up. The most frequently used type of PT was lymphatic drainage (n = 1,061, 36.8%), followed by exercise therapy (n = 1,047, 36.3%) and heat therapy (n = 689, 23.9%). More than three-fourths of treated patients (82%) received 1 or 2 different forms of PT simultaneously. The prescription of PT was associated with the extent of skin fibrosis as measured by the modified Rodnan skin thickness score (10 [41.8% of patients], 11-20 [55.8% of patients], and21 [63.9% of patients]; P0.001). Patients with musculoskeletal involvement (e.g., arthritis, muscle weakness, joint contractures, tendon friction rubs) had a higher chance of receiving PT than patients without these symptoms, with corresponding ORs ranging from 1.96 (95% confidence interval [95% CI] 1.69-2.28) for joint contractures to 3.83 (95% CI 2.89-5.08) for arthritis. When comparing the type of PT prescription across the initial and all follow-up visits from 2003 to 2017, significant alterations with a decreasing frequency of patients receiving PT could be observed (P = 0.001).To our knowledge, this is the first study reporting the use of PT in patients with systemic sclerosis (SSc) in a large cohort. Although SSc is characterized by considerable disability and restriction of motion,40% of patients received PT.

Background Systemic sclerosis (SSc) is a very heterogeneous multisystem connective tissue disease. The majority of affected patients develop initial clinical symptoms between the age of 30 to 50 years. It is not known whether an ageing population affects the clinical phenotype of SSc. Objectives To investigate the relationship of the age at disease onset and clinical characteristics in SSc patients using the registry of the German Network for Systemic Scleroderma. Methods Clinical data of the patient registry, currently including 4021 patients, were evaluated. Three age ranges at disease onset ( 60 years) were correlated with clinical characteristics. Results Among all SSc patients, 27% of patients developed first non-raynaud symptoms at the age 60 years developed significantly (p Conclusions In this registry, nearly one third of patients developed SSc at an age above 60 years. These are mostly of the limited cutanous subtype with frequent PH. These findings have an important influence on recommendations on diagnosis and theray of SSC. Disclosure of Interest None declared

Background: Pulmonary involvement is the leading cause of death in SSc and can manifest as interstitial lung disease (ILD), pulmonary hypertension (PAH) or a combination (ILD-PH). Aim of this analysis was to determine prevalence, clinical characteristics and outcomes of these different forms within the German SSc Network. Methods: SSc pts were analyzed for pulmonary involvement, clinical characteristics and outcome. Results: There were 3699 pts in 42 centers with a mean follow up time of 34.4±12.6 months. At baseline, ILD was frequent (29.5%), while ILD-PH and PAH had lower prevalence (7.5%, 6.1%). At the end of follow up, 32% of SSc pts had ILD, 13% ILD-PH and 7% PAH. ILD and ILD-PH were more frequent in the diffuse form (47%, 12%), while PAH did not differ between subforms. Significant differences in baseline characteristics between PAH vs. ILD-PH vs. ILD were found for age (62, 59, 54 years), sex (males: 15%, 22%, 24%) and smoking prevalence (non-smokers 49%, 63%, 57%). Mean DLCO and FVC were 56% / 93 % for PAH, 49% / 78% for ILD-PH and 56% / 81% for ILD. Significant decreases for DLCO (≥15%) and FVC (≥10%) were found in 45% / 26% in PAH, 45% / 26% for ILD-PH and 36% / 16% in ILD. All-cause mortality was 8.1% for the total cohort and differed significantly between patients without pulmonary involvement (4%), ILD (7.8%), PAH (14.2%), and ILD-PH (21%, p Conclusions: ILD is the most prevalent pulmonary involvement in SSc, while PH-ILD is associated with the most detrimental survival. Significant differences in baseline characteristics of types of pulmonary SSc involvement may help identify patients at risk in the future.

Background Systemic sclerosis (SSc) is a chronic fibrosing autoimmune disease which leads to severe musculoskeletal dysfunction, disability and contractures. Little is known on the type and extent of physical therapy (PT) prescribed to SSc patients in daily practice. Objectives To determine the type and frequency of PT received by SSc patients. Methods The data of 3430 clinically well defined SSc patients registered in the database of the German Network for Systemic Sclerosis were analyzed using SPSS. Results 48,5% (1662/3430) of the patients were treated with PT. The most frequently used form of PT was lymphatic drainage (23,6%/876), followed by physical exercise therapy (22%/817) and paraffin wax bath (10,5%/389). About half of the patients (46,9%) received two or three different forms of PT simultaneously. The prescription of PT did not correlate with the SSc subtype, as 49,5% (503/1016) of dcSSc patients, 50,3% (850/1689) of lcSSc patients and 45,7% (143/313) of SSc-Overlap patients received PT. PT was significantly more often prescribed to patients with pulmonary fibrosis in 51,1% (617/1208), synovitis in 61,6% (299/485) and CK elevation in 61,1% (174/285) (p=0,001–0,029). PT did not correlate with the extent of skin fibrosis as measured by mRSS. Interestingly, patients with joint contractures (45,5%) (388/853) or tendon friction rubs (40,6%) (114/281) received significantly less often PT (p=0,006/ 0,045). Comparing the prescription of PT during the initial period 2003–2008 (49,1%; 1937/3942) with the follow up period 2009–2013 (45,3%; 2217/4899), a significant decrease of PT prescription was observed (p Conclusions Although SSc is characterized by considerable disability and restriction of motion, less than 50% of patients received PT. The significant decrease in PT prescription during recent years may reflect lack of knowledge how to prescribe PT and more restrictive insurance regulations. Disclosure of Interest None declared

Background Lung involvement, i.e. interstitial lung disease (ILD) and pulmonary hypertension (PH), is common in patients with systemic sclerosis (SSc), significantly limiting quality of life and survival. Data on clinical correlations between lung function and clinical subsets of SSc are sparse. Objectives To investigate the relationship of DLCO and clinical characteristics in patients SSc patients within the registry of the German Network for Systemic Scleroderma. Methods Clinical data of the patient registry, currently including DLCO data of 1917 patients were evaluated. In total, these patients were clinically evaluated 5997 times (i.e., at the first visit and during follow-up visits). At the initial visit and during follow-up DLCO levels were correlated with clinical characteristics. Results At initial presentation, 64% of the patients had DLCO levels CI 1.7–2.5) and SSc-Overlap patients (OR, 1.55; p Conclusions Impairment of pulmonary function as determined by diffusing capacity DLCO is more common and more pronounced in patients with dcSSc and SSc-Overlap Syndrome compared to lcSSc. DLCO may be useful for diagnosing and monitoring pulmonary involvement in SSc. Disclosure of Interest None declared

Objectives: The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included were 0.87 ( s . d . = 0.66) and 0.92 ( s . d . = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability.

Objective Although gastrointestinal tract dysfunction is a common feature in patients with systemic sclerosis (SSc; scleroderma), few studies have addressed the pathogenetic mechanisms of gastrointestinal tract involvement in SSc. We previously showed that severe fibrosis and increased expression of profibrotic cytokines are important hallmarks in the gastric wall of patients with SSc. The aim of the present study was to investigate whether immune and/or microvascular abnormalities may account for tissue damage in gastric wall specimens obtained from patients with SSc. Methods Gastric biopsy samples from 27 patients with SSc and 15 healthy control subjects were analyzed by immunohistochemistry for CD45/leukocyte common antigen, CD3/T cells, CD4/T helper cells, CD8/cytotoxic T cells, CD20/B cells, CD14/monocytes, CD68/macrophages, cell adhesion molecules CD11a/lymphocyte function−associated antigen 1 (LFA-1), CD49d/very late activation antigen 4 (VLA-4), CD54/intercellular adhesion molecule 1 (ICAM-1), CD106/vascular cell adhesion molecule 1 (VCAM-1), CD31/platelet endothelial cell adhesion molecule 1, and vascular endothelial growth factor (VEGF). Results T cell infiltration was a prominent finding in gastric specimens from patients with SSc. The CD4+/CD8+ T cell ratio was significantly increased in SSc specimens compared with controls. T cells were found in both lymphocyte aggregates and diffuse infiltrates and strongly expressed the activation markers VLA-4, LFA-1, and ICAM-1. Endothelial cells showed corresponding surface activation with strong expression of VCAM-1 and ICAM-1. Mature B cells were frequently observed arranged in aggregates and rarely were seen in a diffuse pattern. Most lymphocyte aggregates lacked monocyte/macrophages. No difference in microvascular density was observed between SSc specimens and controls. Both SSc and control specimens showed weak or no expression of VEGF. Conclusion Our findings provide the first evidence that endothelial/lymphocyte activation leading to prominent CD4+ T cell infiltration may play a key pathogenetic role within the gastric wall of patients with SSc and may represent an important therapeutic target.

The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P

Background Systemic sclerosis (SSc) is a heterogeneous multisystem connective tissue disease, usually subdivided into the main SSc subsets, e.g. limited (lcSSc), diffuse SSc (dcSSc) and SSc overlap syndromes. However, some patients present with symptoms suggestive of, but not conclusive for a diagnosis of definite SSc. This subset has been referred to as undifferentiated or very early SSc. It was defined as positive RP together with at least one further feature of SSc and/or detectable SSc-specific autoantibodies. Objectives Methods Up to date, more than 3400 patients have been registered within the German network for systemic scleroderma. Disease progress after initial patient registration and further follow-up visits was analysed to determine, whether clinical features in patients with undifferentiated SSc change over time into definite SSc. Results Among 3473 registered patients, 8.1% (282/3473) were diagnosed with undifferentiated SSc. Of these, 87.5% were female with a mean age at onset of 59.9±1.5years. A significant difference was detectable comparing patients with undifferentiated SSc and lcSSc (54.8±0.5years; p 34.0% of undifferentiated SSc patients suffered from sicca symptoms, followed by 31.2% with gastrointestinal (GI) involvement, 30.5% with musculoskeletal involvement, 14.5% with lung fibrosis, 6.0% with heart involvement, 5.0% with pulmonary arterial hypertension (PAH) and 0.4% with renal crisis. Musculoskeletal involvement, sicca symptoms and heart involvement were found in a similar percentage in patients with undifferentiated and lcSSc. Lung fibrosis, PAH and GI involvement occurred significantly less in patients with undifferentiated SSc compared to lcSSc. Within a mean follow-up time of 3.6years, the majority of the patients classified initially as undifferentiated SSc, remained within this subset (76.6%), while only 16.3% converted into lcSSc. 4.6% were classified as dcSSc and 3.2% as SSc overlap syndromes. Conclusions Patients classified as undifferentiated SSc, develop clinical features suggestive of SSc at a significantly older age than other subsets (i.e. 5–10 years). During follow up progression into a limited, diffuse or SSc overlap syndrome subset was observed, however, the majority of undifferentiated SSc patients remained stable and did not develop definite SSc. Disclosure of Interest None declared

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.

It is well known that severe neutropenia, as usually seen in patients with acute leukaemia, aplastic anaemia or secondary to aggressive chemotherapy, predisposes to infections with Gram-negative enteric bacilli,Pseudomonas aeruginosa, Staphylococcus aureus, and to fungal infections. Infection with anaerobes, in contrast, is rare in patients with haematologic malignancy [1]. The spectrum of bacterial pathogens in this patient population has recently broadened, and now includes coagulase-negative staphylococci, viridans group streptococci, and, occasionally, coryneforms and other rather unusual opportunistic organisms. All these microorganisms originate either from the patient's own microflora, especially from the digestive tract, or from the hospital environment after having colonized the patient during the hospital stay [2]. Studies have shown that the incidence of fever during periods of severe neutropenia approaches 100%, and most of these fever episodes actually represent bacterial infection. For more than 20 years, methods for the prevention of bacterial and fungal infections have been under investigation in patients with profound neutropenia. These included decontamination trails, oral or systemic antimicrobial prophylaxis, strict reverse isolation and maintenance of germ-free conditions [3–8], prophylactic granulocyte transfusions [9], and, more recently, the application of haemopoietic growth factors [10, 11]. The method which remains the most widely used is oral antimicrobial prophylaxis, especially with agents for so-called selective decontamination of the intestinal tract.

Systemic sclerosis (SSc) is a chronic connective tissue disease characterised by excessive fibrosis resulting in its most noticeable symptom, the hardened skin. SSc also affects organs including the gastrointestinal (GI) tract, the vascular system, the lungs and the joints. We could previously show that profibrotic cytokines and infiltration of CD4 T lymphocytes are increased in the gastric wall (GW) of SSc patients. In rheumatoid arthritis (RA) we found that certain adipokines have immunomodulatory functions. We therefore analysed localisation of …

From 1972-1983 53 patients underwent bone marrow transplantation. The median age was 18 years (3-41). 27 patients suffered from severe aplastic anaemia, 22 patients had acute leukaemia and 4 patients had chronic granulocytic leukaemia in chronic phase. Out of 22 patients with acute leukaemia, 2 had florid leukaemia, 2 had an early relapse and 18 patients were in first or second remission of their disease. 2/53 patients received a syngeneic transplant, 51/53 patients an allogeneic transplant. 47/51 patients had a HLA-A, B, C-identical, MLC-negative sibling donor, 1/51 had a HLA-A, B-C-identical, MLC-positive sibling donor, 2/51 a HLA-phaenotypical identical parental donor and 1/51 a HLA-identical, MLC-negative unrelated donor. The comparison of the results obtained in patients with severe aplastic anaemia transplanted from 1972-1979 with those transplanted from 1980-1983 shows that the bone marrow transplantation has to be performed in an early stage of the disease before the patients become multiple transfused, sensitized and severely infected and that the conditioning regimen for polytransfused patients has to be more intensive than in untransfused patients. From the patient group transplanted 1972-1979, only 1/14 patients is a long-term survivor in contrast to 8/13 patients transplanted from 1980-1983. 11/22 patients with acute leukaemia are alive between more than 5 years and 14 days after bone marrow transplantation. Only 1/4 patients, who were transplanted not in remission, is alive.(ABSTRACT TRUNCATED AT 250 WORDS)

We have developed a rapid and simple procedure for the elimination of mature T-cells from the donor marrow using a single incubation with the monoclonal antibody Campath-1 and donor complement. This resulted in a reduction of T-cell contamination to a mean of 1%. This regimen reduced the incidence of acute graft-versus-host disease significantly in 21 consecutive bone marrow grafts in 18 patients with leukaemia and non-Hodgkin's lymphoma. Purging was responsible for an increased incidence of graft rejection in HLA-identical transplants (13%).