Background: Interstitial lung disease (ILD) is a frequent and severe manifestation in multi-organ rheumatic musculoskeletal diseases (RMD). The six-minute walking test (6MWT) is a inexpensive, readily available tool in clinical practice for the monitoring of exercise capacity in patients with RMD-ILD. It is however unclear whether the underlying disease or lung involvement correlates with reduced exercise capacity. Objectives: To assess the impact of patient reported disease activity and disability, lung specific characteristics and the sensitivity to change of exercise capacity by the 6 minutes walking distance (6MWD) in patients with RMD-ILD and to compare 6MWD performance in the patients compared to age- and gender-specific reference values [1]. Methods: We followed 109 RMD-ILD patients in our prospective cohort study at Oslo University Hospital. Patients were assessed at baseline and 52 weeks. Exercise capacity using the 6MWD was assessed together with lung function by forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO), overall physical capacity by New York Heart association (NYHA) functional class and self-reported symptoms and disability by validated PROMs. We calculated standardized references values of the 6MWD (1). Changes in the scores values were analyzed by Wilcoxon signed rank test. All correlations were assessed using Spearman correlation. Results: The study population consisted of 38 rheumatoid arthritis (RA), 30 idiopathic inflammatory myopathies (IIM), 24 systemic sclerosis (SSc), 12 primary Sjogren's syndrome (pSS) and 5 mixed connective tissue disease (MCTD)-ILD patients (Table 1). Clinical characteristics and patients reported measures did not differ significantly across the individual RMD-ILD subsets (Table 1). In comparison with the calculated reference values, the RA-ILD patients had reduced 6MWD, with a difference of 175 meters (P<0.001) (Figure 1A). We identified significant correlation between NYHA class and 6MWD, but could not identify any other common variables impacting exercise capacity (Figure1B). Lower lung function impacted exercise capacity only in IIM-ILD patients. While in RA-ILD patients exercise capacity was lower in patients reporting increased fatigue, disability and overall impaired health status, this had no impact in pSS-ILD and only limited impact on patients with IIM and SSc/MCTD-ILD. Conclusion: RA-ILD patients have a lower than expected exercise capacity and this appears to be more strongly influenced by fatigue, overall health status and disability than lung involvement. In the other RMD-ILD patients, we found only minor impact of patient reported outcomes on exercise capacity. REFERENCES: [1] Enright, P. L. & Sherrill, D. L. (1998). Reference equations for the Six-minute Walk in Healthy adults. AM J RESPIR CRIT CARE MED 1998;158:1384-1387. Acknowledgements: NIL. Disclosure of Interests: Mona-Lovise Ramsli: None declared, Torhild Garen: None declared, Phuong Phuong Diep Boehringer-Ingelheim., Yes (to my institution): Boehringer-Ingelheim., Henriette Didriksen: None declared, Emily Violette Langballe Boehringer-Ingelheim, Helena Andersson: None declared, Øyvind Molberg: None declared, Henrik Mangseth: None declared, Michael Durheim Pfizer and AstraZeneca, Yes, (to my institution): Roche and Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp & Dohme and Roche, Boehringer Ingelheim, Janssen.

Background: Interstitial lung disease (ILD) in primary Sjögren's syndrome (pSS) has been reported to be present in 10-15% of patients. There are limited data on the disease course of pSS-ILD, and it is not clear how the ILD in pSS evolves compared to the ILD in other rheumatic musculoskeletal diseases (RMDs) such as systemic sclerosis (SSc), antisynthetase syndrome (ASS) and rheumatoid arthritis (RA). These knowledge gaps are important to fill for clarification whether it is appropriate or not to lump pSS-ILD together with other RMD-ILD types for clinical trial purposes, given the limited treatment options for pSS-ILD. Objectives: Assess proportion and rate of progressive ILD in pSS applying several definitions for progressive ILD and compare to other RMD-ILDs. Methods: We included pSS-ILD patients from well characterized cohorts at two expert RMD-ILD centers (Oslo and Zurich). Eligibility criteria were ILD on HRCT, consecutive annual lung function assessments including forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) and comprehensive serial clinical and imaging assessments. We assessed progressive disease in pSS-ILD and compared it to other RMD-ILDs applying the following definitions for ILD progression: (I)Absolute FVC decline ≥5% and ≥10% over 12 months (II)2022 ATS/ERS/JRS/ALAT guideline progressive pulmonary fibrosis (PPF) criteria with (1) worsening of respiratory symptoms; (2) absolute decline in FVC ≥5% or in DLCO ≥10% and (3) disease progression on HRCT, over 12 months In addition, absolute FVC decline over 12 months was compared between groups. We compared ILD progression across the diseases using descriptive statistics including ANOVA. Results: In total, 647 RMD-ILD patients met the study eligibility criteria and were enrolled in the study cohort. The total cohort included 46 (7%) patients with pSS-ILD, 127 (20%) with ASS-ILD, 79 (12%) with RA-ILD, 65 (10%) with other idiopathic inflammatory myopathies (IIM) and 24 (4%) with mixed connective tissue disease (MCTD) (Table 1). Baseline and 1 year follow-up lung function data was available in 477 and 346 patients, respectively. Patients with pSS-ILD had higher baseline FVC% compared to other RMDs, and higher but impaired DLCO% values (Table 1). In total, we identified 117 (25%) RMD-ILD patients with FVC decline ≥5%, 56 (12%) with FVC decline ≥10% and 53 (15%) patients with PPF (Table 2). Corresponding figures in pSS-ILD were 28 %, 13% and 20%, showing that pSS-ILD was as progressive as other RMD-ILDs using any of the applied definitions (Table 2). Absolute FVC% decline was most pronounced in patients with pSS-ILD compared to other RMD-ILDs despite standard of care treatment (Table 1 and 2). In addition, worsening on HRCT was more pronounced in pSS-ILD than in other groups. Conclusion: In this study, progressive ILD is as frequent in pSS as in the other RMDs assessed. This highlights the urgent need for optimized management approaches including early identification and monitoring of pSS-ILD patients. Our results indicate that it is appropriate to include patients with pSS-ILD in clinical trials with basket approaches. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Marco Sprecher AbbVie, Emily Langballe Boehringer Ingelheim, Phuong Phuong Diep Boehringer Ingelheim, Boehringer Ingelheim, Håvard Fretheim Boehringer Ingelheim, Helena Andersson: None declared, Trond M Aaløkken Boehringer Ingelheim, Cathrine Brunborg: None declared, Cosimo Bruni Eli-Lilly Boehringer Ingelheim, Novartis Foundation for Biomedical Research, AbbVie, Wellcome Trust, Christian Clarenbach Boehringer Ingelheim, GSK, Astra Zeneca, Sanofi, Vifor, Grifols, OM Pharma, CSL Behring, Boehringer Ingelheim, GSK, Astra Zeneca, Sanofi, Vifor, Grifols, OM Pharma, Daiichi Synkyo, CSL Behring, Michael T Durheim Boehringer Ingelheim, Roche, Boehringer Ingelheim, Thomas Frauenfelder Bayer, Bracco, Boehringer Ingelheim, Bayer, Øyvind Molberg: None declared, Oliver Distler Boehringer Ingelheim, Janssen, Medscape, CITUS AG, 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, Horizon, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Orion, Prometheus, Redxpharma, Roivant, Topadur, UCB., Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Novartis, Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp & Dohme, Roche, Boehringer Ingelheim, Janssen.

Aim: To explore if patient global assessment (PGA) is associated with inflammation over time and if associations are explained by other measures of disease activity and function in patients with idiopathic inflammatory myopathies (IIM). Methods: PGA and systemic inflammatory markers prospectively collected over five years were retrieved from the International MyoNet registry for 1200 patients with IIM. Associations between PGA, erythrocyte sedimentation rate (ESR), C -reactive protein (CRP) and creatine kinase (CK) were analyzed using mixed models. Mediation analysis was used to test if the association between PGA and inflammatory markers during the first year of observation could be explained by measures of disease activity and function. Results: PGA improved, and inflammatory markers decreased during the first year of observation. In the mixed models, high levels of inflammatory markers were associated with worse PGA in both men and women across time points during five years of observation. In men, but not in women, the association between elevated ESR, CRP and poorer PGA was explained by measures of function and disease activity. With a few exceptions, the association between improved PGA and reduced inflammatory markers was partially mediated by improvements in all measures of function and disease activity. Conclusion: Increased levels of systemic inflammation are associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health in patients with IIM. Furthermore, the results demonstrate the importance of incorporating PGA as an outcome measure in clinical practice and clinical trials.

Background A subset of patients with connective tissue disease associated interstitial lung disease (CTD-ILD) progresses. These patients have been included in clinical ILD trials as a group despite their different underlying diseases. It has not been studied whether this basket approach of pooling different CTD-ILDs is valid, e.g., if the disease course of the ILDs depends on the underlying CTD. In addition, the impact of immunosuppressive treatment, which CTD-ILD patients receive for ILD or other organ manifestations as a standard of care, is not fully understood. Objectives To assess ILD progression in patients with CTD-ILDs on standard of care treatment. Methods CTD-ILD patients (N=504) from a Norwegian and Swiss cohort fulfilling the respective classification criteria of the underlying CTD with ILD diagnosed on HRCT were included. Data were extracted from prospectively collected local registries. Additional data were extracted from electronic patient records. Change in absolute FVC% predicted over 12 months was calculated. In addition, ILD progression was assessed over 12 months on standard of care treatment, defined as:(I)Absolute decline of FVC (% predicted) ≥10%(II)2022 ATS/ERS/JRS/ALAT guideline criteria including 2/3 of (1) worsening of respiratory symptoms; (2) absolute decline in FVC ≥ 5% or in DLCO ≥ 10% and (3) disease progression on HRCT over 12 monthsMultivariable logistic regression and descriptive statistics were applied. Analyses were adjusted for underlying CTD and immunosuppressive treatment (including corticosteroids any dose, csDMARDs, mycophenolate, cyclophosphamide, CD-20/TNF/ JAK/IL6-inhibitors). Results The total CTD-ILD cohort of 504 patients included 231 (46%) systemic sclerosis (SSc)-ILD, 91 (19%) anti-synthetase syndrome (ASS)-ILD, 82 (16%) rheumatoid arthritis (RA)-ILD, 57 (11%) primary Sjögren syndrome (pSS)-ILD and 43 (9%) mixed connective tissue disease (MCTD)-ILD patients (Table 1). Mean absolute change in FVC% over 12 months was for the entire cohort -0,74% (range -34 to +42%), 57 (13,7%) had an FVC decline ≥10% and 47 (12%) fulfilled the guideline criteria.ILD progression varied between the diagnoses, with SSc-ILD and pSS-ILD showing the strongest absolute FVC decline over 12 months and the highest percentage of progressive patients defined by the 2022 guideline. Additionally, patients with SSc-ILD and MCTD-ILD had more frequent FVC ≥10% events (Table 1).Overall, 240 (62,8%) patients were treated with immunosuppressives (table 1). There was no difference between patients treated and not treated in absolute FVC decline (OR 1.00, 95%CI 0.98-1.02, p= 0.705), and in the percentage of progressive patients according to the guideline criteria (OR 1.00, 95%CI 0.54-1.86, p= 0.995). However, there was less FVC decline ≥10% (OR 0.51, 95% CI 0.28-0.90, p= 0.022) in patients treated with immunosuppressives. Patients with SSc-ILD (11% vs 20%, p=0.059) and pSS-ILD (8% vs 19%, p=0.329) showed numerically less FVC decline ≥10%. The different CTD diagnoses had different patterns of treatment with immunosuppressives, with the majority of RA and ASS-ILD being treated (Table 1). Conclusion In this CTD-ILD cohort, both underlying CTD and immunosuppressive treatment seemed to be associated with different patterns of ILD progression over a 12-month period. This has implications for the enrichment for progressive disease and inclusion of CTD-ILD patients into clinical trials. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Emily Langballe: None declared, Phuong Phuong Diep Speakers bureau: Boehringer-Ingelheim, Consultant of: Boehringer-Ingelheim, Helena Andersson: None declared, Cosimo Bruni Speakers bureau: Eli-Lilly, Consultant of: Boehringer Ingelheim, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC). Educational grants from AbbVie, Håvard Fretheim Speakers bureau: Boehringer Ingelheim, Grant/research support from: Jannsen, Torhild Garen: None declared, Ragnar Gunnarsson: None declared, Øyvind Midtvedt: None declared, Øyvind Molberg: None declared, Øyvind Palm: None declared, Silje Reiseter: None declared, Trond M Aaløkken: None declared, Oliver Distler Speakers bureau: 4PPharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur., Consultant of: 4PPharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Pfizer, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Grant/research support from: Kymera, Mitsubishi Tanabe, Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Jannsen, Medscape, Merck Sharp & Dohme and Roche, Consultant of: ARXX, Boehringer Ingelheim, Genentech, Jannsen, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Jannsen.Table 1pSS(N = 57)ASS(N= 91)SSc(N = 231)RA(N = 82)MCTD(N = 43)Male sex, n (%)10 (18)29 (32)55 (24)37 (45)14 (33)Age at diagnosis, yrs (SD)52 (14,9)49 (15,4)48 (15,0)54 (15,3)39 (17,4)Disease duration, yrs (SD)9,8 (8,7)10,1 (8,2)10,4 (12,4)11,3 (13,2)13,3 (9,7)Immunosuppression, n (n with valid data) (%)28 (46) (60,9)62 (69) (89,9)86 (228)(37,7)47 (50) (94)17 (23) (73,9)Baseline FVC% (SD)91,5 (17,8)79,6 (23,1)88,6 (20,0)73,0 (19,1)85,5 (18,2)Δ FVC% (SD) after 12 months- 2,39 (9,2)-0,37 (10,3)-1,18 (9,3)1,67 (9,0)-0,64 (11,9)FVC decline ≥ 10 %, n (%)5 (13)7 (11)38 (17)3 (5)4 (18)Guideline criteria, n (%)5 (12,8)5 (8,1)34 (14,9)2 (4,5)1 (5,3)

Background Up to 28% of patients with anti-synthetase syndrome (AsyS) have dermatomyositis (DM)-type rashes. However, it is not clear whether ASyS patients with DM-type rashes should be treated similarly to patients with DM or classified as DM in a clinical trial setting. Furthermore, it is not known if presence of DM-type rashes confers an increased risk of DM-specific extramuscular manifestations, such as malignancy. Objectives To compare clinical characteristics, including the frequency of cutaneous, extramuscular features, and malignancy, between adults with ASyS and DM. Methods Using data from the MYONET registry, an adult cohort of DM patients with anti-Mi2/TIF1ɣ/NXP2/SAE/MDA5 autoantibodies, and an ASyS cohort of patients with anti-tRNA synthetase autoantibodies (anti-Jo1/PL7/PL12/OJ/EJ/KS), were identified. Patients with DM sine dermatitis and with dual autoantibody specificities were excluded. Sub-cohorts of ASyS patients with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). Results In total, 737 patients were included (DM, n=251; ASyS, n=486). Within the ASyS cohort, 34% (n=163) had DM-type skin involvement (ASyS-skin). A higher frequency of Raynaud's phenomenon differentiated ASyS-skin from DM (n=72, 44% vs n=34, 14%, p<0.01), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n=155, 62% vs n=73, 45%), V sign (n=69, 28% vs n=22, 14%), periorbital rash (n=53, 21% vs n=27, 17%), and shawl sign (n=89, 36% vs n=15, 9%) differentiated DM from ASyS-skin (all p<0.01). Cancer-associated myositis (CAM) was more frequent in DM (17%) compared to ASyS (3%) and ASyS-skin (3%) cohorts (both p<0.01) (Table 1). Conclusion DM-type rashes are frequent in patients defined as having ASyS; however, certain clinical features differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance or investigation. These findings will help to inform future ASyS-based classification criteria. References [1]Hervier, Baptiste et al. “Hierarchical cluster and survival analyses of antisynthetase syndrome: phenotype and outcome are correlated with anti-tRNA synthetase antibody specificity.” Autoimmunity reviews vol. 12,2 (2012): 210-7.[2]Lilleker, James B et al. “The EuroMyositis registry: an international collaborative tool to facilitate myositis research.” Annals of the rheumatic diseases vol. 77,1 (2018): 30-39. Acknowledgements This publication was supported by researchers at the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the United Kingdom (UK) National Health Service (NHS), the NIHR or the UK Department of Health. Disclosure of Interests Ryan Malcolm Hum: None declared, James B. Lilleker: None declared, Janine Lamb: None declared, Alexander Oldroyd: None declared, William Ollier: None declared, Guochun Wang: None declared, Chanakya Kodishala: None declared, Lucy Wedderburn: None declared, Louise Diederichsen Consultant of: Data safety monitoring board for Corbus Pharmaceuticals, Grant/research support from: Boehringer Ingelheim, Jens Schmidt: None declared, Maria Giovanna Danieli: None declared, Katalin Dankó: None declared, THI PHUONG THUY NGUYEN: None declared, Mónica Vázquez-Del Mercado Espinosa: None declared, Helena Andersson: None declared, Boel De Paepe: None declared, Jan De Bleecker: None declared, Britta Maurer Speakers bureau: Boehringer-Ingelheim, GSK, Novartis, Consultant of: Novartis, Boehringer Ingelheim, Janssen-Cilag, GSK, Grant/research support from: AbbVie, Protagen, Novartis, Medtalk, Pfizer, Roche, Actelion, Mepha, MSD, Liza McCann: None declared, Nicolo Pipitone: None declared, Robert Paul New: None declared, Niels Steen Krogh: None declared, Neil McHugh: None declared, Jiří Vencovský: None declared, Ingrid E. Lundberg Shareholder of: Roche, Novartis, Consultant of: Corbus Pharmaceuticals Inc, Advisory board for Corbus Pharmaceutical, EMD Serono, Argenx, Octapharma, Kezaar, Orphazyme, Pfizer, and Janssen., Grant/research support from: Astra Zeneca, Hector Chinoy: None declared.Table 1Clinical manifestations of diseaseDM (n=251)ASyS (n=486)ASyS-skin (n=163)ASyS-without-skin (n=323)DM vs ASyS Adjusted p-valueDM vs ASyS-skin Adjusted p-valueASyS-skin vs ASyS-without-skin Adjusted p-valueDM-type rashes n (%)Heliotrope Rash155 (62)73 (15)73 (45)0 (0)<0.01<0.01<0.01Gottron's Papules or Sign145 (58)110 (23)110 (68)0 (0)<0.010.66<0.01Violaceous Rash94 (38)51 (11)51 (31)0 (0)<0.010.23<0.01Erythroderma22 (9)9 (2)9 (6)0 (0)<0.010.11<0.01Periorbital Rash53 (21)27 (6)27 (17)0 (0)<0.010.04<0.01V Sign Rash69 (28)22 (5)22 (14)0 (0)<0.01<0.01<0.01Shawl Sign89 (36)15 (3)15 (9)0 (0)<0.01<0.01<0.01Extramuscular manifestations n (%)Periungual Erythema72 (29)75 (15)43 (26)32 (10)<0.010.045<0.01Calcinosis7 (3)9 (2)6 (4)3 (1)0.620.810.15Ulceration11 (4)5 (1)3 (2)2 (1)0.040.650.72Vasculitis4 (2)1 (0.2)0 (0)1 (0.3)0.0450.611Mechanic's Hands11 (4)142 (29)62 (38)80 (25)<0.01<0.01<0.01Raynaud's Phenomenon34 (14)178 (37)72 (44)106 (33)<0.01<0.01<0.01Arthritis29 (12)221 (46)77 (47)144 (45)<0.01<0.011Dysphagia72 (29)88 (18)35 (22)53 (16)<0.010.250.22Alopecia24 (10)26 (5)12 (7)14 (4)0.1710.21Interstitial Lung Disease28 (11)320 (66)100 (61)220 (68)<0.01<0.010.11Cardiac Involvement4 (2)30 (6)14 (9)16 (5)0.03<0.010.20CAM n (%)42 (17)16 (3)5 (3)11 (3)<0.01<0.010.90

Background Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of diseases with systemic inflammation. Inflammation has previously been associated with poor subjective health appraisal in both acute and chronic inflammatory diseases [1-5]. Objectives To explore if the patient-reported outcome measure “patient global assessment” (PGA) is associated with markers of inflammation over time and if associations could be explained by functional measures in patients with IIM. Methods PGA and inflammatory markers longitudinally collected over 5 years were retrieved for 1333 patients with IIM from the international MyoNet registry. Associations between PGA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and creatine kinase (CK) were analyzed with mixed effect regression analyses. Mediation analysis was used to test if the associations between PGA and inflammatory markers could be explained by disease-associated symptoms and signs. Results PGA improved and inflammatory markers decreased during the first year of observation. High levels of ESR and CRP were associated with worse PGA in both men (ESR:b=0.21, 95%CI 0.10-0.32, p<0.001, CRP:b=0.16, 95%CI 0.04-0.29, p=0.012) and women (ESR:b=0.34, 95%CI 0.25-0.42, p<0.001, CRP:b=0.26, 95%CI 0.14-0.37, p<0.001) across time points, and CK was associated with PGA in women (b=0.70, 95%CI 0.48-0.93 p<0.001) but not in men (b=0.07, 95%CI -0.54-0.68, p=0.831). In men, the association between elevated inflammatory markers and poorer PGA was explained by disability and extra-muscular disease activity whereas in women this association could not be explained by any of the included functional measures. With a few exceptions, the association between reduced inflammatory markers and improved PGA during the first year of observation was partially mediated by improvements in all functional measures. Conclusion Higher levels of systemic inflammation were associated with poorer PGA in patients with IIM. In addition to known benefits of lowered inflammation, these findings emphasize the need to reduce systemic inflammation to improve subjective health. References [1]Kananen L, Enroth L, Raitanen J, Jylhävä J, Bürkle A, Moreno-Villanueva M, et al. Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains. Scientific Reports. 2021;11(1):6139.[2]Lodin K, Lekander M, Syk J, Alving K, Petrovic P, Andreasson A. Longitudinal co-variations between inflammatory cytokines, lung function and patient reported outcomes in patients with asthma. PloS one. 2017;12(9):e0185019.[3]Warnoff C, Lekander M, Hemmingsson T, Sorjonen K, Melin B, Andreasson A. Is poor self-rated health associated with low-grade inflammation in 43,110 late adolescent men of the general population? A cross-sectional study. BMJ open. 2016;6(4):e009440.[4]Tanno K, Ohsawa M, Onoda T, Itai K, Sakata K, Tanaka F, et al. Poor self-rated health is significantly associated with elevated C-reactive protein levels in women, but not in men, in the Japanese general population. J Psychosom Res. 2012;73(3):225-31.[5]Lekander M, Elofsson S, Neve IM, Hansson LO, Unden AL. Self-rated health is related to levels of circulating cytokines. Psychosom Med. 2004;66(4):559-63. Acknowledgements On behalf of all MyoNet contributor.s. Disclosure of Interests Karin Lodin: None declared, Fabricio Espinosa-Ortega: None declared, Maryam Dastmalchi: None declared, Helene Alexanderson: None declared, Jiří Vencovský: None declared, Helena Andersson: None declared, Hector Chinoy: None declared, James B. Lilleker: None declared, Niels Steen Krogh: None declared, Robert Paul New: None declared, Samuel Katsuyuki Shinjo: None declared, Britta Maurer: None declared, Zoltán Griger: None declared, Yonit Tavor: None declared, Angela Ceribelli: None declared, Diana Gomez: None declared, Mónica Vázquez-Del Mercado Espinosa: None declared, Dag Leonard: None declared, Anne Erler: None declared, Ingrid E. Lundberg Grant/research support from: I.E.L. has received consulting fees from Corbus Pharmaceuticals, Inc and research grants from Astra Zeneca and has been serving on the advisory board for Corbus Pharmaceutical, EMD Serono. Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, Pfizer and Janssen and has stock shares in Roche and Novartis.Longitudinal associations between PGA and inflammatory markersWomenobs (n)patients (n)b PGACIp-valueMenobs (n)patients (n)b PGACIp-valueESR124475450.340.25;0.42<0.001***ESR110352540.210.10,0.32<0.001***CRP227207330.260.14;0.37<0.001***CRP211073080.160.04;0.290.012*CK328238210.700.48;0.93<0.001***CK311093360.07-0.54;0.680.831*p<0.05, **p<0.01, ***p<0.001. 1.Erythrocyte sedimentation rate. 2.C-reactive protein. 3. Creatine kinase as ratio of upper limit normal.Mixed models with fixed effect coefficients (b) and 95% confidence intervals (bootstrapped based p-values, 20000 repetitions). All models were adjusted for age and included all available data points.

Background Connective tissue disease (CTD) is an umbrella term for a heterogeneous group of autoimmune diseases affecting the connective tissue in various organs. One of the most serious complications associated with CTDs is interstitial lung disease (ILD), which results in significant morbidity and mortality. A subset of CTD-ILD patients shows progressive disease, which is associated with an even worse prognosis. Previous studies have identified dysregulations of biomarkers including CX3CL1, CCL2, CCL17 and CCL18 in systemic sclerosis (SSc) showing an association with ILD [1-4]. For other CTD-ILD it is less clear, which biomarkers are associated with ILD and ILD progression and few studies have assessed circulating biomarkers across CTD-ILDs. Objectives To investigate circulating biomarkers in CTD-ILD and in progressive CTD-ILD patients. Methods Serum samples from SSc (n=292), primary sjogrens syndrome (pSS) (n=132), mixed connective tissue disease (MCTD) (n=162), anti-syntetase syndrome (ASS) (n=72) patients and healthy controls (HC) (n=100) collected at Oslo University Hospital (OUH) were analyzed by ELISA for selected biomarkers (CX3CL1, CCL2, CCL17, CCL18). SSc samples were used as the reference disease to compare with mean levels of serum markers in pSS, ASS and MCTD. ILD was diagnosed on high resolution computed tomography (HRCT). Forced vital capacity (FVC) was available at baseline and 12 +/- 3 months. ILD progression defined as an absolute FVC% predicted decline of ≥10% was assessed. Descriptive statistics and logistic regression with odds ratio (OR) and 95%CI were performed. Results Serum levels of CX3CL1 and CCL18 were significantly higher in all the CTDs (p<0.001) compared to HC. CCL2 and CCL17 levels were significantly higher in SSc (p=0.001 and p<0.001), ASS (p<0.001 and p=0.004) and MCTD (p<0.001 and p<0.001) compared to HC, but not in pSS (p=0.230 and p=0.087). Of all CTD patients, 267/658 (41%) were diagnosed with ILD (table 1). Of these patients 80 (30%) showed ILD progression, where data were obtained for SSc, pSS and ASS (Tabel 1). All the markers were significantly higher in patients with ILD compared to no ILD in SSc and pSS, while only CCL17 was significantly higher inn ASS-ILD and none in MCTD-ILD. When using SSc-ILD as reference disease, serum levels of CX3CL1 were significantly higher in pSS-ILD (p<0.001) and MCTD-ILD (p<0.001), and CCL18 was significantly lower in MCTD-ILD (p<0.001). Serum levels of CCL2 and CCL17 did not significantly differ between SSc-ILD and the other CTD-ILDs (Figure 1A). From logistic regression analysis of the patient with ILD progression, CCL18 (OR: 1.19, 95%CI, p=0.001) were the only marker significantly associated with ILD progression. When adjusting for CTD with SSc as reference disease, the only marker significantly associated with ILD progression was also here CCL18 (OR: 1.06, 95%CI: 1.03-1.09, p<0.001) (Figure 1B). Conclusion In this large CTD cohort, we show that CCL2 and CCL17 are increased across all CTD patients with ILD compared to no ILD, which could help us to identify patients with ILD. ILD progression was only associated with CCL18, which was driven by the SSc-ILD subpopulation. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Henriette Didriksen: None declared, Håvard Fretheim Speakers bureau: Boehringer Ingelheim, Consultant of: Bayer, Grant/research support from: GSK/Actelion, Helena Andersson: None declared, Silje Reiseter: None declared, Ragnar Gunnarsson: None declared, Emily Langballe: None declared, Torhild Garen: None declared, Øyvind Midtvedt: None declared, Thor Ueland: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Janssen, Medscape, Merck, Sharp & Dohme and Roche, Consultant of: ARXX, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck, Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Genentech and Janssen.Table 1Clinical and demographic dataSSc (n=292)pSS (n=132)ASS (n=72)MCTD (n=162)Females, no (%)239 (61)123 (93)48 (67)128 (79)Age at disease onset, yrs (SD)48 (15.4)52 (14.1)49 (12.8)35 (15.7)FVC baseline, % (SD)95 (20.3)99 (12.7)85 (21.8)92 (18.5)ILD, no (%)140 (47.9)16 (12.1)60 (83.3)51 (31.5)ILD progression, n (%)74 (26)3 (19)3 (6)-Mean CCL18, ng/ml49.3 (10.8)47.4 (12.5)50.5 (11.2)43.8 (9.8)Mean CCL2, ng/ml0.6 (0.7)0.5 (0.2)0.9 (0.5)0.7 (0.8)Mean CCL17, ng/ml0.6 (0.5)0.5 (0.5)0.6 (0.5)0.6 (0.6)Mean CX3CL1, ng/ml1.9 (2.5)3.2 (6.3)2.0 (2.9)3.4 (5.6)Figure 1(A) Mean levels of markers in SSc-ILD, pSS-ILD, ASS-ILD and MCTD-ILD, and (B) association of circulating markers with ILD progression using SSc-ILD as the reference.

Background Interstitial lung disease (ILD) in primary Sjögren’s syndrome (pSS) has been reported to be present in 10-15% of patients, but pSS-ILD behavior over time is not well characterized. Objectives Assess the pattern of ILD in pSS, its disease behavior and factors associated with disease progression in a well-characterized pSS-ILD cohort. Methods All pSS patients from the Oslo University Hospital (OUH) were included if ILD was diagnosed on HRCT. Clinical characteristics, lung function tests including forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) and ILD pattern on HRCT assessed by a radiologist were evaluated. We determined ILD progression, defined as absolute FVC decline >5% or absolute DLCO decline >10% over 12 +/-6 months and increasing extent of ILD on HRCT over the observation period. Factors associated with disease progression were chosen based on expert opinion. Descriptive analyses were conducted Results Of 702 pSS patients followed at OUH, we identified 60 pSS patients with ILD with 33 (55%) having follow-up at 12 months (Table 1). Patients with pSS-ILD were characterized by high number of males (18%) and by frequent other extra-pulmonary organ involvement (48%) (Table 1). Mean time from pSS diagnosis to ILD diagnosis was 7.4 years. In 67% ILD was diagnosed after pSS, in 13% simultaneously, in 11% before pSS diagnosis and in 9% unknown. In total, 28 (47%) were diagnosed with lymphocytic interstitial pneumonia (LIP) and 32 (53%) with reticular pattern on HRCT. Over mean follow-up of 10.9 months (SD 4.2), 7/33 (21%) showed a FVC >5% decline, 9/32 (28%) a DLCO >10% decline and 12 (36%) had at least one of these defined lung function declines on standard of care treatment. Treatment was registered as ever used and by any indication. Over an observation period of 15.4 (SD 10.6) years, 27/47 (45%) showed any ILD progression on HRCT. HRCT pattern was not associated with risk of >10% DLCO decline or ILD progression on HCRT. >5% FVC decline occurred more frequently in patients with reticular pattern compared to LIP (6/17 (35%) vs 1/16 (6%), p=0.041). Factors significantly associated with ILD progression on lung function included higher baseline FVC (99% (SD16.4) vs 87% (SD14.9), p=0.032), higher DLCO (81% (SD13.1) vs 67% (SD17.4), p=0.020), increased CRP (2/10 (20%) vs 0/16 (0%), p=0.045) and presence of polyneuropathy (2/9 (22%) vs 1/17 (6%), p=0.045). Table 1. Clinical characteristics, demographics and outcome of pSS with ILD pSS-ILD(n=60) Age at pSS diagnosis, y (SD) 50 (21.9) Time from pSS to ILD diagnosis, y (SD) 7.4 (8.9) Male sex, n (%) 11 (18) Anti-SSA AB, n/50 (%) 46 (92) Increased CRP, n/47 (%) 7 (15) Low complements, n/49 (%) 5 (10) Extra-pulmonary involvement, n/46 (%) 22 (48) Deceased, n (%) 10 (17) Pulmonary involvement FVC% predicted (SD) 91 (18.7) FVC decline>5%, n/33 (%) 7 (21) DLCO% predicted (SD) 70 (20.7) DLCO decline >10%, n/32 (%) 9 (32) ILD progression on HRCT, n/47 (%) 27 (45) Treatment during follow up Rituximab, n (%) 11 (18) Any other immunosuppressive, n (%) 20 (33) Hydroxychloroquine, n (%) 16 (27) Nintedanib, n (%) 1 (2) Lung transplant, n (%) 1 (2) Conclusion A substantial number of patients with pSS-ILD progressed during the time of observation. This highlights the importance of close monitoring and active consideration of treatment options in pSS-ILD. Recommendations for disease management including screening, diagnosis, disease monitoring and treatment for pulmonary involvement in pSS are lacking to date, but are highly needed. Disclosure of Interests Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Jansen, Lilly, Medscape, Merck Sharp & Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Håvard Fretheim Consultant of: Bayer, Grant/research support from: Jansen, Phuong Phuong Diep Speakers bureau: Boehringer Ingelheim, Karoline Lerang: None declared, Helena Andersson: None declared, Øyvind Midtvedt: None declared, Torhild Garen: None declared, Mike Durheim Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim and Roche, Grant/research support from: Boehringer Ingelheim and Roche, Trond M Aaløkken Speakers bureau: Boehringer Ingelheim, Øyvind Palm: None declared, Øyvind Molberg: None declared

BackgroundTakayasu arteritis (TAK) is a rare vasculitis of large vessels, mainly in young women, with a point prevalence of 25.6/106 in a Norwegian population. TAK is most prevalently limited to the aortic arch and its branches (Type 1) among North Europeans (1). Early symptoms include fever, myalgia and loss of appetite. Later, irreversible vascular damage and ischemic symptoms with claudication of the extremities may occur. We have previously observed a reduced life expectancy, mainly due to cardiovascular complications and a median age among those deceased of only 58 years (2). These findings clearly indicate that TAK may have severe impact on the wellbeing of the patients and their physical capacity. Furthermore, being part of the working life is a major component of life but is affected in chronic autoimmune diseases (3,4)Objectives(i) To describe general health status and quality of life in patients with different working status.(ii) To estimate the rates of patients having paid work or receiving disability benefits, compared to the general Norwegian population.MethodsPatients with TAK registered in “The Norwegian Systemic Connective Tissue Disease and Vasculitis Registry” (NOSVAR) were included. All patients fulfilled the American College of Rheumatology classification criteria and/or the modified Ishikawa diagnostic criteria for TAK. (3). General health status was measured with 10-cm visual analogue scale (VAS) of pain and fatigue, ranging from 0 (best possible score) to 10 (worst possible score) and with Patients´ global assessment (PtGA) of health measured by a five-point Likert scale with scores ranging from 1 (very good health) to 5 (very bad health). The SF-36 was applied to measure health related quality of life and included 8 scales with score ranging from 0 (worse) to 100 (best). Disease duration was defined as the time from diagnosis to date of registration. Working full- or part time was defined as paid work. We adjusted for age, gender and residence counties in southeast Norway using reference data from Norway Statistics. Indirect standardization with 95% confidence interval rates was calculated. Descriptive analyses were conducted.ResultsPatients with paid work were more educated compared with those receiving disability benefits (81% vs 19% p=0.031). Patients receiving disability benefits reported higher levels of pain (3,4 vs.1,4, p=0.024) and disease activity (3,8 vs. 0,8, p=0.025), more frequently claudication in legs (83% vs. 17%, p= 0.009) and impaired quality of life measured with SF- 36, physical functioning (66 vs 88, p=0.002) and role physical (32 vs 65, p=0.017) compared to patients with paid work/students (Figure 1).Compared with the age and gender matched general population, the disability rate of female patients was 16 % higher, adjusted ratio (CI 95%) 2 (1,2-3,3), p=0.038. The paid work rate was 51% lower in women with TAK compared to the general population, adjusted ratio (CI 95%) 0,38 (0,23-0,64), p=0.001 .ConclusionTAK-patients receiving disability benefits reported lower health status and lower quality of life by physical functioning and role physical in SF 36. Work disability in female TAK patients was 16 % higher and for paid work 51 % lower compared to the general population.References[1]Gudbrandsson B, Molberg Ø, Garen T, Palm Ø, Arthritis Care Resb (Hoboken), 2017 Sept;69:1384-1390[2]Garen T, Lerang K, Hoffmann-Vold AM, Andersson H, Midtvedt Ø, Brunborg C, Kilian K, Gudbrandsson B, Gunnarsson R, Norby G, Chaudhary A, Thoen J, Forseth KØ, Fresjar K, Førre Ø, Haugen M, Haga HJ, Gran JT, Gilboe IM, Molberg Ø, Palm Ø. Rheumatology (Oxford). 2019 Feb 1;58(2):313-320.[3]Abularrage CJ, Slidell MB, Sidawy AN, Kreishman P, Amdur RL, Arora S. Quality of life of patients with Takayasu’s arteritis. Journal of vascular surgery. 2008;47(1):131-6; discussion 6-7.[4]Janine M Ouimet 1, Janet E Pope, Iris Gutmanis, John Koval Work disability in scleroderma is greater than in rheumatoid arthritis and is predicted by high HAQ scores. 2008;2:44-52. doi: 10.2174/1874312900802010044. Epub 2008 Sep 23.Disclosure of InterestsNone declared

Background There is a gap between how IIM patients are classified in practice and current validated classification criteria 1 . Also, different associations with genetic variations in HLA can inform about different T-cell mechanisms involved in disease pathogenesis. Objectives We aimed to systematically study associations between HLA-DRB1 alleles, clinical manifestations, and autoantibody-defined IIM subgroups. Methods We included 1348 IIM patients from five European countries. An unsupervised cluster analysis was performed using 14 autoantibodies: anti-Jo1, -PL7, -PL12, -EJ, -OJ, -SRP, -U1RNP, -Ro52, -Mi2, -TIF1γ, -MDA5, -PMScl, -SAE1, and -NXP2 to identify patients’ subgroups. Logistic regressions were used to estimate the associations between HLA-DRB1 alleles, clinical manifestations and the identified subgroups. Results Eight subgroups were defined by the autoantibody status (Table 1). Three of the subgroups (1, 2 and 6) have overlapping autoantibodies, while four are almost monospecific (3,4,5 and 7), and one (8) has patients negative for tested autoantibodies. Figure 1 represents the significant associations between HLA-DRB1 alleles and the eight subgroups. Heliotrope rash and Gottron’s sign were significantly more frequent in subgroups 3 (OR:2.2 95%CI:[1.1-4.8], OR:2.6 95%CI:[1.3-5.9], respectively), 4 (OR:12 95%CI:[3.6-75], OR:7.8 95%CI:[2.8-33], respectively) and 7 (OR:22 95%CI:[4.5-385], OR:10 95%CI:[3.1-65], respectively), and Raynaud’s phenomenon was significantly more frequent in subgroup 6 (OR:3.3 95%CI:[1.2-11]). Table 1. Autoantibody-defined subgroups using an unsupervised cluster analysis. Subgroups/ Medoids Variables 1 Ro52 2 U1RNP 3 PMScl 4 Mi2 5 Jo1 6 Jo1/Ro52 7 TIF1 8 None* All n (% ) 137 (10) 183 (14) 107 (8) 65 (5) 119 (9) 140 (10) 78 (6) 519 (39) 1348 (100) Female (% ) 93 (68) 116 (63) 79 (74) 45 (69) 76 (64) 96 (69) 64 (82) 313 (60) 882 (65) Age at diagnosis, median (IQR) 56 (16) 51.5 (23) 51 (25) 57 (22.5) 47.5 (23.25) 52 (19.5) 53.5 (21.75) 58 (22) 55 (23) Autoantibodies Anti-Jo1 0 6 (3) 0 1 (2) 119 (100) 140 (100) 0 0 266 (20) Anti-PL7 7 (5) 13 (7) 0 0 0 0 0 0 20 (1.5) Anti-PL12 5 (4) 3 (2) 1 (1) 0 1 (1) 0 0 0 10 (0.7) Anti-EJ 2 (2) 0 0 0 0 0 0 0 2 (0.1) Anti-OJ 0 7 (4) 0 0 0 0 0 0 7 (0.5) Anti-TIF1 10 (7) 2 (1) 2 (2) 0 0 0 78 (100) 0 92 (7) Anti-Mi2 1 (1) 1 (1) 1 (1) 65 (100) 0 2 (1) 0 0 70 (5) Anti-SAE1 8 (6) 23 (13) 0 0 0 0 0 0 31 (2) Anti-NXP2 1 (1) 23 (13) 1 (1) 0 0 0 0 0 25 (2) Anti-MDA5 9 (7) 10 (6) 1 (1) 1 (2) 0 1 (1) 0 0 22 (2) Anti-SRP 8 (6) 32 (18) 0 0 0 0 0 0 40 (3) Anti-Ro52 137 (100) 16 (9) 0 0 0 140 (100) 0 0 293 (22) Anti-PMScl 11 (8) 1 (1) 107 (100) 0 0 0 0 0 119 (9) Anti-U1RNP 0 79 (43) 0 0 0 3 (2) 0 0 82 (6) *IIM patients negative for the tested autoantibodies. Figure 1. Forest plot of significant associations of HLA. *DRB1 alleles with autoantibody-defined subgroups. Scandinavia includes patients from Denmark, Norway, and Sweden. Conclusion Our study reveals that certain subgroups of IIM patients are characterized by overlap of myositis -specific and -associated autoantibodies, which in turn are associated with different HLA-DRB1 alleles including potential novel associations. These results point to different disease mechanisms in the subgroups, as well as suggest that IIM classification could be improved by integrating broader serological and genetic data. References [1]Parker MJS, Oldroyd A, Roberts ME, et al. The performance of the European League Against Rheumatism/American College of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort. Rheumatology (Oxford). 2019;58(3):468-475. Acknowledgements We thank all the patients who participated in the study. Disclosure of Interests Valerie Leclair: None declared, Angeles Shunashy Galindo-Feria: None declared, Simon Rothwell: None declared, Olga Kryštůfková: None declared, Heřman Mann: None declared, Louise Pyndt Diederichsen: None declared, helena andersson: None declared, Martin Klein: None declared, Sarah Tansley: None declared, Neil McHugh: None declared, Janine Lamb: None declared, Jiří Vencovský Speakers bureau: Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Werfen, Consultant of: Abbvie, Argenx, Boehringer, Eli Lilly, Gilead, Octapharma, Pfizer, UCB, Grant/research support from: Abbvie, Hector Chinoy: None declared, Marie Holmqvist: None declared, Leonid Padyukov: None declared, Ingrid E. Lundberg Shareholder of: Roche and Novartis, Consultant of: Corbus Pharmaceuticals Inc, Astra Zeneca, Bristol Myer´s Squibb, Corbus Pharmaceutical, EMD Serono Research & Development Institute, Argenx, Octapharma, Kezaar, Orphazyme, and Janssen, Grant/research support from: Astra Zeneca, Lina M. Diaz-Gallo: None declared

Background: Interstitial lung disease (ILD) progression in primary Sjögren’s syndrome (pSS-ILD) is poorly characterized. Objective: To asssess ILD progression in pSS-ILD. Methods: All pSS-ILD patients from the Oslo University Hospital were included and clinical characteristics, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and ILD pattern on HRCT assessed. ILD progression was defined as absolute FVC decline >5% or DLCO decline >10% over 12 +/−6 months. Results: We identified 60 pSS-ILD patients with 33 (55%) having followup at 12 months (Table). In 67% ILD was diagnosed after pSS, in 13% simultaneously and in 11% before pSS diagnosis. Over mean 10.9 months, 7/33 (21%) showed FVC >5% decline, 9/32 (28%) DLCO >10% decline and 12 (36%) had any of these. HRCT pattern was only associated with >5% FVC decline (reticular pattern (6/17 (35%) compared to LIP 1/16 (6%), p=0.041). Other factors associated with ILD progression included FVC (99% (SD16.4) vs 87% (SD14.9), p=0.032), DLCO (81% (SD13.1) vs 67% (SD17.4), p=0.020), increased CRP (2/10 (20%) vs 0/16 (0%), p=0.045) and extrapulmonary involvement (2/9 (22%) vs 1/17 (6%), p=0.045). Conclusion: A substantial number of patients with pSS-ILD progressed over 1 year, highlighting the importance of close monitoring and active consideration of treatment approaches in pSS-ILD.

Background: Based on the argument that symptoms define disease, physicians commonly apply the terms “preclinical” or “subclinical” disease to describe patients with disease-related findings but no accompanying symptoms for connective tissue disease associated interstitial lung disease (CTD-ILD). The term subclinical frequently applies to patients with mild ILD changes on high resolution chest tomography (HRCT), normal forced vital capacity (FVC), and without respiratory symptoms. Previous work in systemic sclerosis (SSc)-ILD did show that patients with even minor extent of ILD at baseline often progressed and had increased mortality risk, suggesting that it is not appropriate to define these patients as “subclinical.” Objectives: To identify the prevalence of subclinical ILD across CTD diagnoses, and assess the rate of progression of lung fibrosis compared to CTD without ILD and with clinical ILD. Methods: All CTD patients, including SSc, anti-synthetase syndrome (ASS) and mixed connective tissue disease (MCTD) from the Oslo University Hospital diagnosed before 2015 and assessed for the presence of ILD by HRCT were included. The year 2015 was chosen to secure an observation time of at least five years from ILD diagnosis to study end on 01.01.2021 or time of death. All patients fulfilled the respective CTD classification criteria. Subclinical ILD was defined as an ILD extent <5% by semi-quantitative assessment of baseline HRCT, preserved lung function with FVC >80% predicted and without respiratory symptoms. Clinical ILD was defined as >5% extent of ILD or <5% extent of ILD on HRCT with respiratory symtoms or FVC<80%. The outcome was ILD progression, defined as increasing extent of ILD from basline to follow-up HRCT by semi-quantitative assessment. Vital status was available in all patients and mortality was evaluated. Descriptive statistical analyses were conducted and time to ILD progression determined by Kaplan-Meier estimates. Results: We identified 525 CTD patients, including 296 with SSc, 135 with MCTD and 94 with ASS who had conducted a baseline HRCT. Of these, 227 (43%) had no ILD, 67 (13%) subclinical and 231 (44%) clinical ILD (Table). Of the 67 subclinical ILD patients, 45 (15%) had SSc, 13 (10%) MCTD and 9 (10%) ASS of thespecific cohorts. Over a median time of 4.5 years between baseline and follow-up HRCT, 95/395 (24%) showed progression of ILD, including 72 (26%) SSc and 23 (19%) MCTD patients. Disease progression frequently occurred in both subclinical ILD (38%) and clinical ILD (51%) patients (Figure). Age, gender, underlying CTD, and baseline lung function were not predictive for the progression of lung fibrosis. Progression was too infrequent to allow for meaningful multivariable regression analyses. After a median observation period of 12 years, 153 (29%) of the patients died. The 1-, 5- and 10-year survival rates in those without ILD, subclinical and clinical ILD were 97%/97%/99%, 88%/91%/82%, and 82%/85%/68% (p<0.001), respectively. Table 1. Clinical characteristics, demographics and outcome No ILD (n=227 ) Subclinical ILD (n=67 ) Clinical ILD (n=231 ) Age, y (SD) 50 (15.4) 51 (14.4) 52 (15.3) Male sex, n (%) 89 (39) 22 (33) 111 (48) Deceased, n (%) 50 (22) 12 (18) 91 (39) Observation period, y median (range) 13.7 (18.6) 13.9 (17.9) 11.5 (17.1) FVC% (SD) 97 (18.6) 99 (17.9) 81 (20.9) FVC decline% (SD) -0.70 (11.1) -0.81 (16.5) -1.61 (15.9) DLCO% (SD) 73 (19.4) 73 (16.9) 55 (17.4) Extent of ILD% (SD) 0 (0) 2.3 (1.5) 19.3 (16.8) ILD progression% (SD) 0.08 (1.0) 3.1 (6.2) 3.6 (9.9) ILD progressors, n (%) 3 (2) 20 (38) 72 (51) Figure 1. Time to ILD progression in CTD without ILD, with subclinical and clinical ILD Conclusion: Subclinical ILD is frequently present across CTDs and progresses over time in a substantial subgroup of patients, comparable to patients with clinical ILD. Our findings question the terms sub- and preclinical ILD, which may potentially lead to a suboptimal “watchful waiting management strategy”. Monitoring all CTD patients with any ILD is of high importance to identify disease progression early. Disclosure of Interests: Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Lilly and Medscape, Consultant of: Actelion, Boehringer Ingelheim, Bayer, ARXX, and Medscape, Grant/research support from: Boehringer Ingelheim, Helena Andersson: None declared, Silje Reiseter: None declared, Håvard Fretheim Consultant of: Actelion, Bayer., Imon Barua: None declared, Torhild Garen: None declared, Øyvind Midtvedt: None declared, Ragnar Gunnarsson: None declared, Mike Durheim Speakers bureau: Boehringer Ingelheim and Roche, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, Trond M Aaløkken: None declared, Øyvind Molberg: None declared

Background Mortality as an outcome of disease’s severity and causes of death can give extended insight into the nature of each specific diagnose and highlight distinct needs for monitoring. In connective tissue diseases (CTD) and systemic vasculitides, mortality and causes of death have been studied within most single diseases, but with heterogeneity of the studies and widely varying results. Studies applying similar methods across the diagnoses are lacking. Consequently, it is difficult to compare causes of death between the different diagnoses.1 Objectives To identify the causes of death within different CTDs and systemic vasculitides. Methods We performed a prospective, observational, controlled study between 1999 and 2017 of adult patients (at least 18 years of age) with diagnosis of CTD or vasculitides. All patients were included in the Norwegian connective tissue disease and vasculitis Registry (NOSVAR). In total, 2140 patients were diagnosed and followed up until death or study end by April 31th 2017. To avoid bias by selection, we included only incident cases, excluding patients with diagnoses set prior to 1999. Moreover, cases with a disease course not consistent with the initial diagnoses were excluded. Causes of death were identified by linking NOSVAR to the Norwegian Causes of Death Registry and by reviewing hospital charts. We divided the causes of death into the main groups of cardiovascular diseases (CVD), neoplasms, chronic respiratory disease (CRD), infections and other (gastrointestinal, renal insufficiency and trauma. To compare causes of death to the general population we used data from WHO Mortality Database, Causes of death.2 Results During a mean (SD) follow-up time of 9.2 years (4.7), 279 patients (13%) deceased. The major causes of death were, in descending order of frequency; CVD (27%), neoplasms (25%), CRD (16%), infections (11%), gastrointestinal manifestations (4%), renal insufficiency (2%). Data from the general population, adjusted for age and gender, showed that deaths by CVD, CRD and infections were more prevalent among the patients.2 The leading causes of death are shown in figure 1. In Takayasu arteritis and lSSc, CVD was the most frequent cause of death; (56%) and (41%), respectively. More than half of the patients (53%) with antisynthetase syndrome died of CRD. Those with dematomyositis died most frequently of neoplasms (50%). Conclusions Compared to general population, patients with CTD and vasculitidis died more often of CVD, CRD and infections. CVD as a cause of death was most prevalent in patients with Takayasu arteritis, giant cell arteritis and systemic sclerosis, while neoplasm was the major cause of death in dermatomyositis. In antisynthetase syndrome, both CRD was the major causes of death. The study gives the clinician valuable information on how to monitoring the different CTDs and vasculitidis regarding serious outcome. References [1] Toledano E, Candelas G, Rosales Z, Martinez Prada C, Leon L, Abasolo L, et al. A meta-analysis of mortality in rheumatic diseases. Reumatologia clinical2012;8(6):334–41. [2] University of Washington, Causes of Death (COD) visualization VizHub. https:/vizhub.healthdata.org/cod/University of Washington;2017 [updated 2017cited2017]. Disclosure of Interest None declared

OBJECTIVES:To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD).METHODS:The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2).RESULTS:445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005).CONCLUSIONS:In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.

Background Gastrointestinal tract (GIT) involvement in systemic sclerosis (SSc) is common, occurring in 50–90% of the patients (1). However, there is limited knowledge of self reported GIT symptoms affecting patients in daily life. Objectives To describe frequency and severity of self reported gastrointestinal symptoms in a large SSc cohort and evaluate possible correlations between special clinical characteristics and GIT-symptoms. Methods Patients from the The Norwegian Systemic Connective Tissue Disease and Vasculitis Registry (NOSVAR) who fulfilled the 2013 ACR/EULAR SSc criteria were included (N=245)). The patients completed the UCLA SCTC GIT 2.0 questionnaire which comprises seven clinical symptoms; Reflux, distention/bloating, diarrhea, fecal soilage, social functioning, emotional well-being and constipation. All variables are scored from better to worse in health related quality of life (HRQL) with a mean total score of 2.8. In addition we used the visual analogue scale on intestinal problems (VAS-GIT) of the Scleroderma Health Assessment Questionnaire (SHAQ) with a maximum score of 3. Disease duration was defined as time from diagnosis to the completion of the questionnaires. Possible correlations were tested by Spearman9s correlation coefficient. Results Patient characteristics and frequencies of the different GIT symptoms are presented in Table 1. Distention bloating, reflux and diarrhea were the most frequent symptoms reported (80%, 69% and 61%, respectively. The least reported symptom was fecal soilage (16%) (Figure 1). Mean (SD) total GIT score was 0.42 (0.41), indicating mild symptoms. The seven subscales ranged from mean (SD) 0.22 (0.55) for fecal soilage to mean (SD) 0.95 (0.50) for distention/bloating. Mean (SD) VAS-GIT score was 0.33 (0.37) and correlated strongly with the mean total UCLA-GIT score (0.667, p<0.001). Female sex and disease duration correlated weakly with mean total UCLA-GIT score (r=-.234, r=199, respectively), as did positive anticentromere-antibody (r=.229).No correlation was found between mean total UCLA-GIT score and subset of SSc, interstitial lung disease, pulmonary hypertension, digital ulcers, Rodnan skin score or Raynaud. Conclusions This study describes a high frequency of self-reported gastrointestinal symptoms in systemic sclerosis patients classified as mild to moderate symtoms. Positive anticentromere-antibody, disease duration and female sex had a minor impact on mean total UCLA-GIT score. The correlation between mean total UCLA-GIT score and the VAS-GIT score of the SHAQ was highly significant indicating a good conformity between the tests. References Forbes A, Marie I: Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology (Oxford) 2009;48 Suppl 3:36–9. Disclosure of Interest None declared

Background The clinical phenotype of the antisynthetase syndrome (AS) has been related with the underlying autoantibody specificity. The typical disease triad (arthritis, myositis, and interstitial lung disease -ILD) is common in anti Jo-1 + AS, whereas isolated ILD is associated with anti PL-7 and PL-12 Ab. The majority of anti Jo-1 + patients without all triad findings at the onset (incomplete ASSD) will develop lacking features during the followup Objectives To assess the triad clinical spectrum time course in non anti Jo-1 + AS Methods The study cohort included patients + for anti-EJ, OJ, PL-7, or PL-12 Ab with at least 1 triad finding. Clinical features were retrospectively collected and analyzed Results we included 65 non anti Jo-1 + AS (7 anti EJ, 4 anti OJ, 30 anti PL-12, 24 anti PL-7; 49 females, 16 males). In median, age at disease onset was 53 years (IQR 42–64), diagnostic delay 9 months (IQR 3–23.5), followup 60 months (IQR 20.5–113). Patients9 characteristics are reported in Table 1. During the followup, 22/61 patients with incomplete AS developed new triad findings, in median 12 months (IQR 6–27) after disease onset. The frequency of incomplete AS developing new triad findings and the length of followup were significantly reduced in non anti Jo-1 + patients with respect to our corresponding anti Jo-1 + cohort (respectively: 22/61 vs 138/220, p<0.001; median 60 months, IQR 18.5–113 vs median 75 months, IQR 39–134; p=0.002) Conclusions In non anti Jo-1 + patients the ex novo occurrence of classic triad finding is common, but less frequent than in anti Jo-1 + patients. The different length of followup may explain at least partly this difference References Cavagna L, et al. Medicine (Baltimore) 2015;94:e1144 Disclosure of Interest None declared

Background Inflammatory myopathies including the Antisynthetase syndrome (ASS) is often complicated by interstitial lung disease (ILD), with impact on morbidity and mortality (1). There is increasing focus on the ILD component of the ASS, but knowledge about long term pulmonary outcome is still limited. Objectives To perform a longitudinal assessment of pulmonary function tests (PFT) in a well-defined cohort of ASS-patients with long term follow up. Methods The ASS-cohort at Oslo University Hospital includes 97 patients diagnosed from 1994-2011. Serial PFT data available for retrospective analyses were available in 94 of these patients. PFT measurements included Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1) and diffusing capacity of the lung for Carbon monoxide (DLCO). PFT data were captured by systematic review of patient charts from symptom onset to study end (at December 31st 2014) or time of death. The earliest PFT identified was defined as the baseline PFT and the examination closest to study end or the time of death was defined as the follow-up PFT. The study was approved by the regional committee of health and medical research ethics in South-East Norway. Paired samples T-test and independent T-test were used to evaluate statistical significance (p<0.05). Results The study cohort included 65 female and 29 male ASS patients (77 anti Jo-1, 7 anti-PL-7 and 10 anti-PL-12) with median age at diagnosis of 49 years. At the end of the study period 62 of the patients were alive and 32 (34%) had died. At the time of the follow-up PFT, 90/94 patients were on immunosuppressive therapy. The median time from baseline to follow up PFT was 61 months, but differed between the living and deceased subsets (Table). In the total cohort, there were no significant differences in PFT values from baseline to follow-up; FVC -0.008 (p<0.933), FEV1 0.061 (p<0.369) and DLCO -0.312 (p<0.208). Subset analyses showed that the deceased patients, except for FVC at baseline, had consistently lower PFT values than the living patients (Table).We also observed a reduction in mean FVC and FEV1 values from baseline to follow-up in the deceased group, but not in the living group (Table). Conclusions In this study, on 94 ASS patients, we found no significant differences in pulmonary function parameters during a median follow up time of 61 months. These data indicate that pulmonary function may be rather stable in treated ASS-patients. The patients who died during the observation period had lower PFT values than the patients who survived, supporting the notion that PFTs have prognostic value in the ASS. Further analyses are required to fully evaluate the described data set. References Marie I et al. Short-term and long-term outcome of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients. Arthritis Rheum Nov;63(11):3439-47 Disclosure of Interest None declared