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Background:Systemic sclerosis (SSc) is a multiorgan disease but, to date, only few definitions of the various organ manifestation specific for SSc exist. When available, these definitions are mainly derived from other diseases, i.e. interstitial lung disease (ILD), where definitions are adopted from idiopathic pulmonary fibrosis (IPF). For comparison of clinical studies and inclusion of patients in randomized clinical trials, standardization of definitions for organ involvement and behaviour over time is of utmost importance.Objectives:To establish expert consensus on definitions of presence of organ involvement, severity of involvement, progression, stability and improvement of organ involvement, and end-stage organ disease.Methods:Ten SSc experts from EUSTAR centres formed the steering committee to conduct the EUSTAR study CP-125. In the first stage, a list of items for the definitions on different organs was created based on a narrative literature search and based on availability of the variables collected in the EUSTAR database. In the second step, using an online survey, the experts were asked to assess the proposed items and add additional items felt to be important to define the respective definitions. Finally, during four online meetings, the steering committee discussed the previous results using the nominal group technique (NGT) and voted on each of the statements (Figure 1). The parameters voted for by more than 75% of the experts were regarded as acceptable to be included in the different definitions.Results:The literature search revealed 179 definitions from 820 papers. After expert evaluation, 199 items were suggested for 9 organ domains including (1) Lung - ILD; (2) Lung – pulmonary hypertension (PH); (3) Heart; (4) Kidney; (5) Skin; (6) Digital ulcers; (7) Arthritis; (8) Muscle; (9) Gastrointestinal tract. During the NGT meetings, definitions for five categories were discussed in each organ domain including the presence of organ involvement, severity of organ involvement, disease progression, disease improvement and end-stage organ involvement. The list of items selected by the online survey was presented and each voting member was asked to discuss the relevance of these items. Of 74 tools proposed and endorsed items to describe organ involvement in SSc; 9 definitions for presence, 7 definitions for severity, 9 definitions for progression, 4 definitions for improvement and 4 for end-organ disease were agreed on (Table 1).Conclusion:A core set of data driven, consensus-based definitions for different organ involvements and disease courses has been defined applying a robust and comprehensive methodology. These definitions are recommended by this SSc expert group to be used as interim tools for research studies.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Anna-Maria Hoffmann-Vold Boehringer Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Novartis and Roche. Consultant for ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp & Dohme and Roche., Boehringer Ingelheim, Janssen, Liubov Petelytska Research grant from Swiss National Research Foundation/Scholars at risk, Imon Barua: None declared, Cosimo Bruni Boehringer Ingelheim, Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), Novartis Foundation for Bio-medical Research, EMDO Foundation. Educational grants from AbbVie and Wellcome Trust. Congress participation support from Boehringer Ingelheim., Corrado Campochiaro: None declared, Ana Maria Gheorghiu: None declared, Alain LESCOAT: None declared, Madelon Vonk Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen Pharmaceutical Companies of Johnson & Johnson, MSD, Novartis, and Roche, Boehringer Ingelheim and Janssen Pharmaceutical Companies of Johnson & Johnson, Boehringer Ingelheim, Ferrer, Galapagos and Janssen Pharmaceutical Companies of Johnson & Johnson, Ilaria Galetti: None declared, Armando Gabrielli: None declared, Oliver Distler 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 and UCB, Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143). Co-founder of 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 and UCB, Boehringer Ingelheim, Kymera, Mitsubishi Tanabe.

Background:Clinical trials in patients with ILDs generally include a 52-week treatment period. Shorter trials would help speed up drug development and reduce the time that patients receive placebo.Objectives:To assess the prognostic value of change in FVC at week 12 or 24 for change in FVC at week 52, and for ILD progression over 52 weeks, in patients with autoimmune disease-related ILDs.Methods:Data were pooled from the placebo group of the SENSCIS trial in patients with fibrosing ILD associated with systemic sclerosis and the patients with progressive fibrosing autoimmune disease-related ILDs in the placebo group of the INBUILD trial. Using a linear regression model, we assessed the prognostic ability of absolute changes in FVC % predicted at week 12 or 24 for absolute change in FVC % predicted at week 52. Using a logistic regression model, we assessed absolute changes in FVC % predicted at week 12 or 24 as predictors of ILD progression (absolute decline in FVC % predicted ≥5% or death) over 52 weeks.Results:The correlation with absolute change in FVC % predicted at week 52 was stronger for the change at week 24 (r=0.59; n=328) than for the change at week 12 (r=0.46; n=326) (Figures 1A and B). The risk of ILD progression over 52 weeks was lower for each 2.5% increase in FVC % predicted from baseline to week 12 (odds ratio 0.51 [95% CI 0.42, 0.62]; p<0.001]) and for each 2.5% increase in FVC % predicted from baseline to week 24 (odds ratio 0.41 [95% CI 0.33, 0.51]; p<0.001]).Conclusion:In clinical trials in patients with autoimmune disease-associated ILDs, changes in FVC at week 12 and 24 were moderately correlated with changes in FVC at week 52, and were associated with the risk of ILD progression or death over 52 weeks.REFERENCES:NIL.Acknowledgements:The SENSCIS and INBUILD trials were supported by Boehringer Ingelheim International GmbH.Disclosure of Interests:Anna-Maria Hoffmann-Vold Dr Hoffmann-Vold reports being a paid instructor for Boehringer Ingelheim., Dr Hoffmann-Vold reports speaker fees from Boehringer Ingelheim, Janssen, Medscape, Merck Sharp & Dohme, Novartis and Roche., Dr Hoffmann-Vold reports consulting fees from ARXX, Bristol-Myers Squibb, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp & Dohme and Roche., Dr Hoffmann-Vold reports grant/research support from Boehringer Ingelheim and Janssen., Margarida Alves Margarida Alves is an employee of Boehringer Ingelheim., Corinna Miede Corinna Miede is an employee of mainanalytics GmbH, Sulzbach (Taunus), Germany, which was contracted by Boehringer Ingelheim to assist with these analyses., Oliver Distler Professor Distler reports speaker fees from Bayer, Boehringer Ingelheim, Janssen and Medscape., Professor Distler reports consulting fees from 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant Siences, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos, Glenmark, Horizon, Inventiva, Kymera, Lupin, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Pfizer, Prometheus, Redxpharna, Roivant, Sanofi and Topadur., Professor Distler reports grant/research support from Kymera and Mitsubishi Tanabe.

Background Sex differences in the incidences of cancers become a critical issue in both cancer research and the development of precision medicine. However, details in these differences have not been well reported. We provide a comprehensive analysis of sexual dimorphism in human cancers. Methods We analyzed four sets of cancer incidence data from the SEER (USA, 1975–2015), from the Cancer Registry at Mayo Clinic (1970–2015), from Sweden (1970–2015), and from the World Cancer Report in 2012. Results We found that all human cancers had statistically significant sexual dimorphism with male dominance in the United States and mostly significant in the Mayo Clinic, Sweden, and the world data, except for thyroid cancer, which is female-dominant. Conclusions Sexual dimorphism is a clear but mostly neglected phenotype for most human cancers regarding the clinical practice of cancer. We expect that our study will facilitate the mechanistic studies of sexual dimorphism in human cancers. We believe that fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of individualized precision medicine beginning from the sex-specific diagnosis, prognosis, and treatment.

Background:Preliminary data indicate that COMPERA 2.0 may be the most accurate tool for risk stratification in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH). Additionally, we have discovered that adding data on diffusion capacity of carbon monoxide (DLCO) to the risk assessment may improve accuracy. To be suitable for risk stratification, DLCO should display sensitivity to change at individual level and have an impact on mortality. Whether DLCO fulfills these criteria are to date unknown.Objectives:This study aims to evaluate relative and absolute changes in DLCO during 12 months from PAH diagnosis and their impact on mortality.Methods:We included SSc patients at Oslo University Hospital who underwent a right heart catheterization (RHC) between 2005 and 2020.1.All patients fulfilled the new PAH criteria (mean pulmonary arterial pressure >20 mmHg, pulmonary artery wedge pressure ≤15 mmHg and pulmonary vascular resistance >2 WU).2.All patients had available DLCO% predicted at time of PAH-diagnosis (±3 months) and after 12 months (±3 months).An improvement in DLCO was defined as an increase in DLCO% predicted of ≥5%. A worsening was defined as a decrease in DLCO% predicted of >5% and stable DLCO was considered a change of±5%. The use of upfront PAH-therapy was registered. We constructed Kaplan-Meier curves for mortality analysis.Results:Out of 106 patients diagnosed with PAH, 54 (51%) had a DLCO% predicted measurement available both at the time of diagnosis and after 12 months (Table 1). We identified 10 (19%) patients with DLCO improvement, 17 (32%) with worsening, and 27 (50%) with stable DLCO.Over a mean observation period of 98 months, 53 (56%) patients died, with a trend towards better survival in patients with improvement in DLCO (Figure 1). 5 (50%) died in the improved DLCO group, 10 (59%) in the worsened group and 12 (44%) in the DLCO stable group.Conclusion:We show that DLCO is sensitive to change in SSc patients with PAH. There was a trend towards better survival in patients who did not deteriorate in DLCO during the first year after PAH diagnosis. This supports our findings that DLCO should be taken into account in the risk stratification of SSc-PAH patients at the time of PAH diagnosis.REFERENCES:NIL.Table 1.Baseline characteristicsAll patients (n=54)Improved DLCO (n=10)Worsened DLCO (n=17)Stable DLCO (n=27)Age at PAH diagnosis, mean years (SD)64.65 (11)64 (8)64 (11)65 (12)Female sex, n (%)43 (80%)8 (80)14 (82)21 (78)Anti-centromere antibody, n (%)28 (61%)6 (60)10 (58)17 (63)Digital ulcers ever, n (%)22 (41%)3 (30)7 (41)12 (44)Six-minute walk distance, m (SD)412 (121)423 (98)399 (120)417 (137)WHO-FC III and IV, n (%)32 (56%)4 (40)9 (53)17 (63)NT-proBNP, ng/L (SD)153 (215)38 (25)219 (274)148 (196)COMPERA 2.0 low risk+intermediate low, n (%)31 (57)9 (90)9 (53)13 (48)COMPERA 2.0 intermediate-high, n (%)16 (30)0 (0)6 (35)10 (37)COMPERA 2.0 high risk, n (%)5 (9)0 (0)2 (12)3 (11)DLCO baseline, % predicted (SD)47 (15)41 (12)58 (14)43 (14)mPAP, mmHg (SD)33.17 (12.4)34 (16)35 (12)32 (11)PVR, wood units (SD)5.72 (SD 5.4)5.7 (4.2)6.2 (6.7)5.5 (4.3)Cardiac index, l/min/m2 (SD)2.78 (SD 0.75)2.8 (0.7)3.1 (1.1)2.6 (0.4)Follow-up time, months (SD)98 (48)113 (67)104 (47)89 (40)No upfront treatment18 (33)3 (30)7 (41)8 (30)Upfront monotreatment26 (48)5 (50)3 (18)15 (56)Upfront duotreatment10 (19)2 (20)4 (23)4 (15)SSc: systemic sclerosis; PAH: pulmonary arterial hypertension; lcSSc: limited cutaneous systemic sclerosis; ACA: anti-centromere antibodies; NYHA: New York Heart Functional Classification; mPAP: mean pulmonary arterial pressure; PVR: pulmonary vascular resistance;Figure 1.Kaplan Meier Curve showing time from PAH-diagnosis to death, segregated by change in DLCO% at 12 months follow-up.Acknowledgements:NIL.Disclosure of Interests:Håvard Fretheim Boehringer Ingelheim, Hilde Jenssen Bjørkekjær: None declared, Øyvind Midtvedt: None declared, Thao Nguyen: None declared, Hu Yi: None declared, Arne Andreassen Janssen, Janssen, Michael T Durheim Pfizer and AstraZeneca, Roche and Boehringer Ingelheim, Phuong Phuong Diep Boehringer-Ingelheim., Boehringer-Ingelheim., Torhild Garen: None declared, Øyvind Molberg: None declared, 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 autoimmune disease is one of the leading causes of morbidity and mortality. Current treatments slow but do not stop decline in lung function, and novel treatments are needed. In a Phase II study in patients with idiopathic pulmonary fibrosis (IPF), the preferential phosphodiesterase 4B inhibitor BI 1015550 prevented lung function decline over 12 weeks with an acceptable safety profile.[1] BI 1015550 is currently being evaluated compared with placebo over at least 52 weeks in randomised Phase III trials: in IPF (FIBRONEER-IPF) and in progressive pulmonary fibrosis (PPF) (FIBRONEER-ILD), which includes patients with autoimmune disease ILD.Objectives:To report the baseline demographics and disease characteristics of the autoimmune disease ILD patient subgroup enrolled in the FIBRONEER-ILD trial.Methods:This double-blind, randomised, placebo-controlled study (NCT05321082) is being conducted in 44 countries. Patients aged ≥18 years with a diagnosis of pulmonary fibrosis other than IPF that met the definition of progression, as well as baseline forced vital capacity (FVC) ≥45% predicted and diffusing capacity of the lung for carbon monoxide (DLco) ≥25% predicted, were eligible for this study. Patients were randomised in a 1:1:1 ratio to BI 1015550 9 mg, BI 1015550 18 mg, or placebo twice daily for at least 52 weeks. Randomisation was stratified by high-resolution computed tomography imaging pattern (usual interstitial pneumonia [UIP]-like vs other fibrotic patterns) and presence of background antifibrotic treatment.Patients receiving cyclophosphamide, tocilizumab, mycophenolate, rituximab or high-dose steroids (prednisone >15 mg/day or equivalent) were excluded. The primary endpoint is absolute change from baseline in FVC (mL) at Week 52.Results:Of 1,780 patients screened, 938 were randomised and 905 received treatment. A total of 352 (39%) treated patients had autoimmune disease ILD, of which rheumatoid arthritis and systemic sclerosis were the predominant diseases (Table 1). The median age of all patients with autoimmune disease ILD was 65 years (range 26–86 years), 166 (47%) were male, 122 (35%) were on nintedanib at baseline and 230 (65%) were not on antifibrotic treatment. Most patients (>98%) were White or Asian, with more White patients in the antifibrotic group and more Asian patients in the non-antifibrotic group. Median FVC was 69% predicted and median DLco was 48% predicted for all patients. A UIP or UIP-like pattern was identified in 266 patients (76%). Patients receiving background antifibrotics had a longer median time from diagnosis of autoimmune disease ILD to study entry than those not receiving antifibrotics. Baseline characteristics by background antifibrotic use are shown in the Table 1. This analysis is based on interim data taken on 10 November 2023. Updated data will be presented at the congress.Conclusion:The FIBRONEER-ILD trial includes a substantial number of patients with autoimmune disease ILD and will provide insights into the efficacy and safety of BI 1015550 in patients with PPF with autoimmune disease ILD. Characteristics of patients enrolled in the FIBRONEER-ILD trial are consistent with other Phase III trials.REFERENCES:[1] Richeldi, L, et al. N Engl J Med 2022; 386:2178–2187.Acknowledgements:This trial was supported and funded by Boehringer Ingelheim. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment for the development of the abstract. Kris Deal, BSc, of Nucleus Global provided writing, editorial support and formatting assistance, which was contracted and funded by Boehringer Ingelheim. Boehringer Ingelheim was given the opportunity to review the abstract for medical and scientific accuracy as well as intellectual property considerations.Disclosure of Interests:Anna-Maria Hoffmann-Vold Boehringer Ingelheim, ARXX, Janssen, Lilly, Medscape, Merck Sharp & Dohme, Roche and Actelion, Boehringer Ingelheim, Jannsen, ARXX, Medscape, Roche and Actelion, Boehringer Ingelheim and Janssen, Toby M. Maher Boehringer Ingelheim and Roche/Genentech, Boehringer Ingelheim, Roche/Genentech, AstraZeneca, Bayer, Blade Therapeutics, Bristol Myers Squibb, Galapagos, Galecto, GlaxoSmithKline, IQVIA, Pliant Therapeutics, Respivant, Theravance and Veracyte, Luca Richeldi Boehringer Ingelheim, Zambon and Cipla, Biogen, Celgene, Nitto, Pliant Therapeutics, Toray, Bristol Myers Squibb, Respivant and CSL Behring, Boehringer Ingelheim and the Italian Medicine Agency, Ingo Sabatschus Current employee of Boehringer Ingelheim, Madhu Kanakapura Current employee of Boehringer Ingelheim., Daniel Wachtlin Current employee of Boehringer Ingelheim., Carl Coeck Current employee of Boehringer Ingelheim., Shervin Assassi Boehringer Ingelheim, Novartis, AbbVie, CSL Behring, AstraZeneca and aTyr Pharma, Boehringer Ingelheim, Momenta and Janssen

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:Systemic sclerosis (SSc) is a chronic multi-system autoimmune disease associated with disability and reduced quality of life. SSc specific patient reported outcome measures (PROMs) are in use for this disease-group to understand the complexity and impact of the disease on the patients’ health status better. Other PROMs are generic, as the EuroQol Five-Dimensional descriptive system (EQ-5D), used to evaluate quality of life, and frequently included as secondary endpoints in randomized trials.Objectives:To describe health status in a Norwegian SSc cohort compared with population norms and to assess change over time measured with EQ-5D questionnaire.Methods:The EQ-5D-5L was included as secondary endpoint in the Norwegian 20 week randomized ReSScue trial. The first part of this PROM consists of five dimensions (mobility, self-care, usual activities pain/discomfort and anxiety/depression) with five answers (1=no problems, 2=moderate problems, 3=severe problems, 4=extreme problems, 5=unable to do). The EQ-5D-5L index was calculated by crosswalk index values using the United Kingdom (UK) Dolan value set in absence of a scoring algorithm for Norway. The index value reflects how good or bad the health state is according to the preferences of the general population of a country/region. Results vary from -0.59 (health worse than dead) and 1 (perfect health). The second part of the questionnaire consists of a single visual analogue scale (VAS) through which patients are asked to rate their health of the day from 0-100 were 0 means the worst health Patients age- and sex matched normative data were obtained from the first Norwegian population norms for the EQ-5D-5L consisted of 12790 randomly selected Norwegian citizens (1713 woman) who were aged 18 years and older [1]. Standardized response mean (SRM) was computed and interpreted according to Cohen`s effect size index, in which 0.2 = small difference, 0.5 = moderate difference, and 0.8 = more as a large difference.Results:The study cohort included 67 SSc patients, with mean age 61 years and mean disease duration of 10 years (Table 1). In the EQ-5D dimensions, proportion of patients reporting problems compared to population norms was 96.9 % vs 69 % (p<0.001) for pain and 53.8% vs 29 % (p=0.003) for activity (Figure 1A). The changes from baseline to week 12 and 20 in patients reporting problems are shown in Figure 1B. The mean (SD) difference between patients and the Norwegian norms in the EQ-5D index score was small -0.033 (-0,16), p=0.147). The EQ5D VAS assessing “your own health today” was at baseline 61.7 (18) showing a mean difference (SD) of -16.7(19), (p<0.001) compared to the Norwegian norms. Overall the repeated measures analyses adjusted for age and gender showed no change over time for the EQ5D-index (SRM 0.02 (95% CI -0.4-0.4; p=0.105) or for the EQ-5D VAS (SRM -0.01 (95% CI -0.2-0.2; p=0.958.Conclusion:Compared to the population norms the EQ-5D dimensions pain, activity and anxiety as well as the EQ-5D VAS were significantly impaired in SSc patients. Nor the EQ-5D index score or the EQ-5D VAS showed sensitivity to change.REFERENCES:[1] Garratt AM et.al. Norwegian population norms for the EQ-5d-5L; results from a general population survey.Acknowledgements:NIL.Disclosure of Interests:Torhild Garen: None declared, Cristina Nita: None declared, Håvard Fretheim: None declared, Imon Barua: None declared, Maylen N Carstens: None declared, Henriette Didriksen: None declared, Vikas K. Sarna: None declared, Øyvind Midtvedt: None declared, Øyvind Molberg: None declared, 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.

BackgroundThe IgG4-related disease (IgG4-RD) responder index (RI) is a validated tool to assess disease activity in IgG4-RD [1]. The RI reflects symptoms attributable to active IgG4-RD as well as relevant findings from the physical examination, imaging and laboratory evaluations, with higher scores reflecting more active disease. Multiorgan involvement and higher RI scores were identified as risk factors for relapse [2], indicating a need for more aggressive treatment. Whole-body 18F-FDG PET/CT is a sensitive technique for detecting foci of active inflammation, but its use is limited by cost and availability. Furthermore, whether 18F-FDG PET/CT detects additional organ manifestations which influence RI and treatment decisions, is largely unknown.ObjectivesTo compare performance of a pure clinical RI model (c-RI) and a c-RI with addition of 18F-FDG PET/CT (c-PET-RI) in a well-characterized Norwegian IgG4-RD cohort.MethodsAdult patients with IgG4-RD seen at the Oslo University Hospital were included if they had performed both 18F-FDG PET/CT and a comprehensive assessment by a rheumatologist within a four-week interval. In each patient, we calculated c-RI from symptoms, clinical examination, and laboratory studies, and c-PET-RI from the c-RI plus the score from pathological 18F-FDG organ uptake on the whole-body PET. Both indices were calculated using data from NOSVAR research registry and electronic medical records. We defined IgG4-RD disease activity as low if RI was ≤ 3 and high if RI was > 3 points. We assessed associations of elevated CRP and serum IgG4 (s-IgG4) with reclassification (discrepancy change in disease activity scores (c-PET-RI – c-RI)) by applying logistic regression with odds ratio (OR) and 95% CI to identify patients in which performing 18F-FDG PET/CT is likely to change treatment decisions.ResultsThe study cohort included 53 IgG4-RD patients, of whom 30 had c-RI ≤ 3 points, consistent with low disease activity. In 15/30 patients (50%) with c-RI ≤ 3, the corresponding c-PET-RI was > 3 points, consistent with high disease activity. In these 15 patients, the mean increase in RI points from the 18F-FDG PET/CT was 6.4 (range 2-12). We found that 14 of these 15 patients (93%) had elevated s-IgG4 and 6 (40%) had elevated CRP. In logistic regression analysis, elevated s-IgG4, but not CRP, was strongly associated with reclassification to high disease activity after18F-FDG PET/CT (OR 16.0, 95% CI 1.7-154.6, p = 0.017). Of the 9 patients with c-RI ≤ 3 and normal s-IgG4, only one (11%) was reclassified to high disease activity after 18F-FDG PET/CT.ConclusionIn IgG4-RD patients with low disease activity by clinical and laboratory assessment (c-RI), elevated s-IgG4 is associated with detection of asymptomatic organ involvement by 18F-FDG PET/CT (c-PET-RI). Hence, evaluation with 18F-FDG PET/CT should be considered in patients with c-RI ≤ 3 points and elevated s-IgG4 to tailor management. In contrast, in patients with c-RI ≤ 3 points and normal s-IgG4, the added yield of 18F-FDG PET/CT appears to be low.References[1]Wallace ZS et al. Arthritis Care Res (Hoboken). 2018;70(11):1671-1678[2]Zongfei J et al. Arthritis Research & Therapy. 2022;24(1):106.Table 1.Total cohort (n = 53)Treatment naïve at time of 18F-FDG PET/CT, n (%)35 (66)c-RI high disease activity (RI > 3), n (%)23 (43)c-PET-RI high disease activity (RI > 3), n (%)38 (72)Factors associated with reclassification to high disease activity after 18F-FDG PET/CTOR95% CIp-valueElevated s-IgG4 (> 2.01 g/L)16.01.7-154.60.017s-IgG4 (per g/L unit increase)1.51.1-2.20.020CRP (per mg/L unit increase)1.10.9-1.30.317Acknowledgements:NIL.Disclosure of InterestsJens Vikse Speakers bureau: Boehringer-Ingelheim, Novartis, Consultant of: Jupiter Life Science, Novartis, Øyvind Midtvedt: None declared, Øyvind Molberg: None declared, Bjørg Tilde Svanes Fevang Speakers bureau: UCB, Consultant of: Lilly, Øyvind Palm: None declared, Torhild Garen: None declared, Katrine Brække Norheim: None declared, Mona Revheim: None declared, Kjersti Johnsrud: None declared, Håvard Fretheim Speakers bureau: Boehringer Ingelheim, Consultant of: Bayer, Grant/research support from: GSK/Actelion, Marianne Wallenius: None declared, Gunnstein Bakland Consultant of: UCB, 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.

Background:Interstitial lung disease (ILD) is the main cause of death in patients with systemic sclerosis (SSc). While impaired lung function with forced vital capacity (FVC) <70% of the expected reference value and extensive lung fibrosis by hogh resolution of chest tomography (HRCT) predict excess mortality in SSc, the risk conferred by less advanced ILD is not fully clear. This question has major clinical implications. If even mild SSc-ILD is associated with overall mortality and, more specifically, respiratory causes of death, there is a potential need for aggressive and better-defined management approaches early in the disease.Objectives:To assess respiratory causes of deaths in SSc-ILD patients and evaluate the impact of general, SSc-, and lung characteristics on respiratory-caused mortality in patients with preserved lung function.Methods:The study cohort included SSc-ILD patients (N=323) from the Norwegian SSc cohort who fulfilled the 2013 ACR/EULAR classification criteria for SSc, had ILD diagnosed by HRCT, and had prospective clinical data available from the local NOSVAR registry. The Norwegian national population registry provided vital status. We obtained causes of death from death certificates and by chart review and segregated them into respiratory and non-respiratory causes. General, SSc-specific, and lung characteristics were determined for associations with respiratory causes of death. The severity of ILD was defined as mild or severe ILD based on lung function (FVC% predicted ≥/<70%), the extent of ILD on HRCT 2). We used logistic regression to assess the impact of the pre-defined characteristics on respiratory-caused mortality in mild ILD based on lung function.Results:Out of 323 SSc-ILD patients, 132 (41%) were deceased. Causes of death were available for 99 (76%) patients. Of these, 24 (24%) died of respiratory causes, with 67% dying of respiratory tract infections and 33% of respiratory failure. Among the 24 patients who died of respiratory causes, 50% had FVC ≥70%, 57% had ≤10% extent of ILD by HRCT, and 44% had reported absence of respiratory symptoms mean 1.1 year prior to death. Next, we aimed to identify clinical characteristics of patients dying of respiratory caused mortality with preserved lung function. We compared the characteristics of the 12 SSc-ILD patients with preserved lung function (defined as FVC ≥70%) who died of respiratory causes to 104 surviving peers. We found that older age, male sex, progressive ILD defined as FVC decline, the presence of respiratory symptoms, reduced six-minute walking distance (6MWD), and the development of pulmonary hypertension (PH) were associated with mortality despite preserved lung function (Table 1). The main cause of respiratory deaths in these patients was respiratory tract infections (75%). Interestingly, no specific SSc manifestations were identified to be associated with respiratory-caused mortality in these patients (Table 1 and Figure 1).Conclusion:A significant proportion of SSc-ILD patients who died of respiratory causes had preserved lung function and did not progress to more severe, end-stage lung disease. Our results highlight the importance of preventing the onset of ILD, as well as halting its progression, even in cases of mild ILD, to improve ILD-associated survival in SSc patients.REFERENCES:NIL.Figure 1.Patient characteristics associated with a respiratory cause of death in SSc-ILD patients with FVC>70% at time point of deathAcknowledgements:NIL.Disclosure of Interests: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, Håvard Fretheim Boehringer Ingelheim, Roche, Emily Langballe Boehringer Ingelheim, Hilde Jenssen Bjørkekjær Jannsen, Jannsen, Henriette Didriksen: None declared, Phuong Phuong Diep Boehringer Ingelheim, Helena Andersson: None declared, Ragnar Gunnarsson CSL Vifor, Michael T Durheim Boehringer Ingelheim, Roche, Boehringer Ingelheim, Torhild Garen: None declared, Øyvind Midtvedt: None declared, Trond M Aaløkken Boehringer Ingelheim, 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 and UCB.

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 monthsIn 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-LillyBoehringer 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.