Association of Anti-Synthetase Antibody Subtypes with Radiographic Progression of Interstitial Lung Disease in Anti-Synthetase Syndrome: An Analysis of the CLASS Project Database

Daphne Rivero Gallegos¹, Francisca Bozan², Sangmee Bae³, Giovanni Zanframundo⁴, Sara Faghihi-Kashani⁵, Iazsmin Bauer Ventura⁶, Eduardo Dourado⁷, Gianluca sambataro⁸, Akira Yoshida⁹, Tamera J Corte¹⁰, Francesco Bonella¹¹, Tracy J Doyle¹², david fiorentino¹³, Miguel Angel Gonzalez-Gay¹⁴, marie Hudson¹⁵, Masataka Kuwana¹⁶, Antonella Notarnicola¹⁷, Andrew Mammen¹⁸, Neil McHugh¹⁹, Frederick Miller²⁰, Carlomaurizio Montecucco²¹, Chester Oddis²², Jorge Rojas-Serrano²³, Jens Schmidt²⁴, Carlo A. Scire²⁵, Albert Selva-O’Callaghan²⁶, Victoria Werth²⁷, Rohit Aggarwal²⁸ and Lorenzo Cavagna²⁹, and CLASS project participating investigators, ¹INER, Ciudad de México, Mexico State, Mexico, ²Hospital Clinico Universidad de Chile, Santiago, Chile, ³UCLA, Los Angeles, CA, ⁴Università di Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, Milano, Italy, ⁵Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, San Francisco, CA, ⁶University of Chicago, Chicago, IL, ⁷Unidade Local de Saúde da Região de Aveiro, Aveiro, Portugal, ⁸University of Catania, Catania, Italy, ⁹Nippon Medical School Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan, ¹⁰Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia, ¹¹Center for interstitial and rare lung diseases, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany, ¹²Brigham and Women's Hospital, West Roxbury, MA, ¹³Department of Dermatology, Stanford University School of Medicine, Stanford, CA, Palo Alto, CA, ¹⁴University of Cantabria, Fundación Jimenez Díaz, Madrid, Madrid, Spain, ¹⁵McGill University, Montreal, QC, Canada, ¹⁶Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Japan, Tokyo, Japan, ¹⁷Karolinska University Hospital and Karolinska Institutet, Stockholm, Stockholms Lan, Sweden, ¹⁸NIH, Bethesda, MD, ¹⁹University of Bath, Bath, United Kingdom, ²⁰NIH, NIEHS, Chapel Hill, NC, ²¹IRCCS policlinico S. Matteo foundation, University of Pavia, Pavia, Italy, ²²Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, ²³National Institute of Respiratory Diseases, Ismael Cosío Villegas, Mexico City, Mexico, ²⁴University Medical Center Goettingen, Göttingen, Germany, ²⁵University of Milano Bicocca, Milan, Italy, ²⁶Systemic Autoimmune Disease Unit, Vall d’Hebron Institute of Research, Barcelona, Spain, ²⁷University of Pennsylvania, Wynnewood, PA, ²⁸Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA, Pittsburgh, PA, ²⁹University of Pavia and Fondazione IRCCS Policlinico San Matteo Hospital of Pavia, Pavia, Pavia, Italy

Meeting: ACR Convergence 2024

Keywords: Autoantibody(ies), Myopathies, pulmonary

Session Information

Date: Monday, November 18, 2024

Title: Muscle Biology, Myositis & Myopathies – Basic & Clinical Science Poster III

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: In anti-synthetase syndrome (ASSD), clinical presentations vary from isolated interstitial lung disease (ILD) to systemic multi-organ manifestations. Several studies emphasize the crucial role of the antibody subtype in determining the clinical features, survival rates, and High resolution computed tomography (HRCT) patterns of ILD between anti-Jo-1 and non-Jo-1 ASSD-ILD patients. The aim of the study was to compare the demographic, clinical, laboratory and radiographic profiles of Jo-1 antibody-positive versus non-Jo-1 antibody-positive ILD patients and the associations between antibody subtype on ILD evolution.

Methods: The Classification Criteria for Anti-Synthetase Syndrome (CLASS) project database was used as the primary data source, with data collected from 92 centers in 30 countries. Cases were classified by the treating physician and validated by the CLASS core team based on the clinical picture; local anti-ARS antibodies detected by any method were also considered. To compare characteristics between anti-Jo-1 and non-Jo-1 patients, the Chi-square test was used to analyze categorical variables, and the Student’s t-test or Mann-Whitney U-test was used for continuous variables, depending on their distribution. The severity of ILD involvement was assessed on the last HRCT evaluated by the treating physician in those patients with follow-up data. It was classified as mild, moderate and severe. A multivariate logistic regression model was performed to identify possible associations of ILD severity at radiographic follow-up with antibody subtype and adjusted for age, sex, ethnicity, baseline forced vital capacity (FVC), and HRCT pattern.

Results: A total of 1784 cases were included, 1103 Jo-1(62%) and 687 non- Jo-1(38%); mean age was lower in the Jo-1subgroup, 50.5 vs. 55.7 years. Anti-Jo-1 patients showed a higher frequency of mechanic’s hands and musculoskeletal manifestations. Non-Jo-1 patients had more frequent respiratory symptoms and lower lung function (DLCO and FVC; Table 1).A follow-up HRCT and pulmonary function test (PFTs) data was available in 514 (28.8%) and 603 (33.8%) patients, respectively. After 1 to 2 years from initial presentation, 45.7% of all patients were identified as having mild, 43.8% moderate, and 10.5% severe ILD. Severe ILD on HRCT was more frequent in non-Jo-1(14.5% vs. 7.8%, p< 0.001). There was also a higher frequency of ILD clinical progression (13.0 vs. 9.3, p=0.003) and ILD progression on PFTs (17.4% vs. 13.4%, p=0.01) in non-Jo-1 patients (Table 2). In the multivariate analysis, the variables associated with the severity of ILD on HRCT at follow-up were UIP pattern (aOR: 7.54; 95% CI: 2.68-21.21; p=< 0.001), baseline FVC (aOR: 0.95; 95% CI: 0.93-0.98; p=< 0.001) and PL-7 antibody positivity (aOR: 3.61; 95% CI: 1.37- 9.51; p=0.009) (Table 3).

Conclusion: Non-Jo-1 patients have a higher frequency of respiratory symptoms and more severe ILD than Jo-1 patients. In addition, PL-7 antibody positivity independently predicts the radiographic severity of ILD during follow-up.

Disclosures: D. Rivero Gallegos: None; F. Bozan: None; S. Bae: None; G. Zanframundo: None; S. Faghihi-Kashani: None; I. Bauer Ventura: None; E. Dourado: Bial, 6; G. sambataro: Boehringer-Ingelheim, 6; A. Yoshida: None; T. J Corte: 4D, 2, 5, Avalyn Therapeutics, 1, 2, 5, Boehringer-Ingelheim, 1, 2, 5, 6, 12, Support for attending meetings and/or travel, Bridge Biotherapeutics, 1, 2, 5, Bristol-Myers Squibb (BMS), 1, 2, 5, 6, 12, Support for attending meetings and/or travel, Cincera, 2, DevPro, 1, 2, Endeavour BioMedicine, 1, 2, Pharmaxis, 2, 5, Pliant, 1, 2, 5, Roche, 1, 2, 5, 6; F. Bonella: None; T. J Doyle: Bayer, 5, Sanofi, 3; d. fiorentino: Argenyx, 2, biogen, 2, bus, 2, johnson & johnson, 2, kyverna, 2, 5, Pfizer, 2, Priovant, 5, 12, gift, Serono, 5, usb, 2; M. Gonzalez-Gay: None; m. Hudson: AstraZeneca, 5, Boehringer-Ingelheim, 5, Bristol-Myers Squibb(BMS), 5, Pfizer, 5; M. Kuwana: Asahi Kasei Pharma, 6, AstraZeneca, 2, Boehringer Ingelheim, 2, 6, Chugai, 2, 6, GSK, 2, MBL, 9, Ono Pharmaceuticals, 6; A. Notarnicola: Boehringer-Ingelheim, 1, 6; A. Mammen: None; N. McHugh: None; F. Miller: None; C. Montecucco: None; C. Oddis: Abcuro, 5, Alexion, 5, Argenx, 5, Boehringer Ingelheim, 5, CSL Behring, 5, EMD Serono, 5, Janssen, 5, Pfizer, 5, Priovant, 5; J. Rojas-Serrano: None; J. Schmidt: CSL Behring, 2, 6, 12, Support for attending meetings and/or travel, Grifols, 2, Janssen, 2, Kezar, 5, Takeda, 2, 6, UCB, 6; C. Scire: None; A. Selva-O’Callaghan: None; V. Werth: AbbVie/Abbott, 2, Alpine immune sciences, 2, Amgen, 1, 5, anaptysbio, 2, AstraZeneca, 2, 5, Biogen, 2, 5, BMS, 2, 5, Cabaletta Bio, 2, Calyx, 2, Caribou, 2, Corbus, 5, CSL Behring, 2, 5, Cugene, 2, Evommune, 2, Gilead, 2, 5, GSK, 2, Horizon, 2, 5, Immunovant, 2, Innovaderm, 2, Janssen, 2, Lilly, 2, Merck, 2, Nuvig Pharmaceuticals, 2, Pfizer, 2, 5, Priovant, 5, Regeneron, 1, 5, Rome Pharmaceuticals, 2, 5, Sanofi, 2, Takeda, 2, UCB, 2, Ventus, 2, 5, Viela, 5, Xencor, 2; R. Aggarwal: Alexion, 2, ANI Pharmaceuticals, 2, Argenx, 2, AstraZeneca, 2, Boehringer-Ingelheim, 2, 5, Bristol-Myers Squibb(BMS), 2, 5, CabalettaBio, 2, Capella Bioscience, 2, Capstanx, 2, Corbus, 2, CSL Behring, 2, EMD Serono, 2, 5, Galapagos, 2, Horizon Therapeutics, 2, I-Cell, 2, Immunovant, 2, Janssen, 1, 2, 5, Kezar, 2, Kyverna, 2, Lilly, 2, Mallinckrodt, 5, Manta Medicines Corporation, 2, Merck, 2, Novartis, 2, Nuvig Therapeutics, 2, Octapharma, 2, Pfizer, 2, 5, Q32, 5, Roivant, 2, Sanofi, 2, Teva, 2; L. Cavagna: None.

To cite this abstract in AMA style:

Rivero Gallegos D, Bozan F, Bae S, Zanframundo G, Faghihi-Kashani S, Bauer Ventura I, Dourado E, sambataro G, Yoshida A, J Corte T, Bonella F, J Doyle T, fiorentino d, Gonzalez-Gay M, Hudson m, Kuwana M, Notarnicola A, Mammen A, McHugh N, Miller F, Montecucco C, Oddis C, Rojas-Serrano J, Schmidt J, Scire C, Selva-O’Callaghan A, Werth V, Aggarwal R, Cavagna L. Association of Anti-Synthetase Antibody Subtypes with Radiographic Progression of Interstitial Lung Disease in Anti-Synthetase Syndrome: An Analysis of the CLASS Project Database [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/association-of-anti-synthetase-antibody-subtypes-with-radiographic-progression-of-interstitial-lung-disease-in-anti-synthetase-syndrome-an-analysis-of-the-class-project-database/. Accessed .

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