ANTIBODY PREDICTORS OF PROGNOSIS IN IDIOPATHIC INFLAMMATORY MYOPATHY ASSOCIATED INTERSTITIAL LUNG DISEASE

J. Hannah, A. Lawrence, J. Martinovic, M. Naqvi, S. S. Ali, C. Stock, C. Owens, A. Devaraj, L. Pollard, S. Agarwal, B. Atienza-Mateo, A. Patel, A. West, K. Tinsley, H. Robbie, F. Chua, B. Lams, A. Wells, S. Norton, J. Galloway, E. Renzoni, P. GordonKing’s College Hospitals NHS Trust, Department of Rheumatology, London, United Kingdom King’s College London, Department of Academic Rheumatology, London, United Kingdom Guys and St Thomas’ NHS Trust, Department of Respiratory Medicine, London, United Kingdom Royal Brompton and Harefield Hospitals, Interstitial Lung Disease Unit, London, United Kingdom University Hospital Lewisham, Department of Rheumatology, London, United Kingdom Marques de Valdecilla University Hospital, Division of Rheumatology, Santander, Spain King’s College Hospitals NHS Trust, Department of Respiratory Medicine, London, United Kingdom King’s College Hospitals NHS Trust, Department of Radiology, London, United Kingdom  Background IIM-ILD follows a varied clinical course. Serological profile can help predict clinical phenotype, but impact on ILD prognosis is less clear. Objectives This multicentre UK cohort study examines whether serological profile can predict mortality and change in lung function over time. Methods Patients with IIM-ILD were identified in 3 NHS trusts from local databases. Adults with ILD meeting IIM diagnostic criteria or Interstitial Pneumonia with Autoimmune Features (IPAF) with Myositis Specific Antibodies (MSA) were included. Baseline characteristics from time of presentation were compared across antibody groups and across survivors/deceased at 2 years. Survival analysis looking at time to death (or lung transplant) for duration of available follow-up was modelled by Cox-Proportional Hazards comparing each antibody individually to all others. Models were adjusted for age, gender, ethnicity, presence of overlap CTD/malignancy, smoking and site. Regression models were also used to observe trends in lung function parameters over time. Results Of 430 included patients, 68% were female, 46% were of White ethnicity. 81% met IIM criteria, 19% were IPAF. Mean follow up duration was 4.3 years. Common antibodies were to Ro52, Jo1, PL12, MDA5 (n=195, 126, 44 & 32 respectively). 10% had evidence of pulmonary hypertension within 1 year of diagnosis, 4% had malignancy within 3 years. Baseline characteristics of survivors vs fatal cases at 2 years showed survivors were younger (51.4 vs 61.7 years), more likely to have never smoked (69% vs 44%), less likely to have been hospitalised at diagnosis (15% vs 52%) and had a lower Charleson Comorbidity Index. Survivors had lower CRP, higher CK & higher baseline FEV1/FVC/TLCO. Imbalance in age, BMI, CK and comorbidity status were seen across antibody groups. MDA5 had the highest adjusted hazard ratio (HR) for mortality of 4.59 (95%CI 2.10-10.01). Kaplan-Meier curve shows high early mortality in this group. Anti-synthetase antibodies (ARS) carried a reduced risk of mortality (HR 0.63), however individually Jo1 had low HR (0.61, 95%CI 0.4-0.87) and PL7 had high HR (2.07, 95%CI 1.44-2.99). RNP showed worse prognosis on adjusted analysis (HR 1.88, 95%CI 1.25-2.84) (Table 1). Regression models suggest that compared to other antibodies, %pred FVC in MDA5 improves over the first 3 years, in PL7 it drops, and in Jo1 it is no different (Figure 1). MDA5 % pred FEV1 also showed improvement, but in Ku it was lower than other antibodies from 21 months. There were no significant differences in % pred TLCO between antibodies. Table 1. Antibody n Deaths/Transplant Univariate HR p value Multivariate HR p value Jo1 126 21 0.56 (0.35, 0.91) 0.020 0.61 (0.42, 0.87) 0.006 PL12 44 10 0.90 (0.47, 1.73) 0.748 1.06 (0.90, 1.26) 0.482 PL7 26 11 2.29 (1.22, 4.31) 0.010 2.07 (1.44, 2.99) <0.001 EJ 16 * 0.63 (0.15, 2.56) 0.517 0.65 (0.30, 1.41) 0.271 OJ 9 * 0.51 (0.07, 3.68) 0.505 0.36 (0.01, 8.50) 0.529 Mi2 19 * 1.31 (0.48, 3.58) 0.603 0.89 (0.27, 2.90) 0.848 SRP 16 * 1.00 (0.32, 3.17) 1.000 0.82 (0.18, 3.73) 0.797 MDA5 32 11 2.90 (1.53, 5.49) 0.001 4.59 (2.10, 10.01) <0.001 PMScl 40 8 0.89 (0.43, 1.85) 0.764 0.66 (0.40, 1.09) 0.105 RNP 30 12 1.48 (0.80, 2.72) 0.208 1.88 (1.25, 2.84) 0.003 Ku 13 * 1.16 (0.37, 3.66) 0.804 1.78 (0.36, 8.77) 0.477 Negative 32 7 0.96 (0.45, 2.08) 0.924 0.90 (0.49, 1.65) 0.740 Ro52 195 40 1.13 (0.75, 1.70) 0.568 1.15 (0.74, 1.80) 0.525 All ARS 215 39 0.58 (0.38, 0.87) 0.009 0.63 (0.52, 0.77) <0.001 * counts of < 5 suppressed for anonymity Figure 1. Image/graph: Conclusion There is strong evidence that antibody status associates with clinical outcomes, both in terms of progression of lung disease and mortality, suggesting pathogenetic differences. MDA5 predicts a high risk of death early on in disease course, whilst Jo1 associates with lower mortality. PL7 and RNP were additional antibodies associating with higher mortality. Difference between Jo1 and PL7 highlights variation within anti-synthetase syndrome. Paradoxically, if an MDA5 positive person survived the early disease phase, there was evidence that lung function can recover, which may reflect different MDA5 subpopulations. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Jennifer Hannah: None declared, Alexandra Lawrence: None declared, Jennifer Martinovic: None declared, Marium Naqvi: None declared, Saadia Sasha Ali: None declared, Carmel Stock: None declared, Cara Owens: None declared, Anand Devaraj Consultant of: Boehringer Ingelhime, Brainomix, Louise Pollard: None declared, Sangita Agarwal: None declared, Belén Atienza-Mateo: None declared, Amit Patel: None declared, Alex West: None declared, Kate Tinsley: None declared, Hasti Robbie: None declared, Felix Chua: None declared, Boris Lams: None declared, Athol Wells Speakers bureau: Boehringer Ingelheim, Roche, Veracyte, Consultant of: Boehringer Ingelheim, Roche, Veracyte, Sam Norton: None declared, James Galloway: None declared, Elisabetta Renzoni: None declared, Patrick Gordon Speakers bureau: UCB, Consultant of: Eli Lilly, Galapagos, Grant/research support from: Corbus Pharmaceuticals. Keywords: Autoantibodies, Myositis, Lungs DOI: 10.1136/annrheumdis-2023-eular.2831Citation: , volume 82, supplement 1, year 2023, page 955Session: Scleroderma, myositis and related syndromes (Poster View)