Preventive effects of early immunosuppressive treatment on the development of interstitial lung disease in systemic sclerosis
Author:
Velauthapillai Arthiha1ORCID, Bootsma M F R1ORCID, Bruni Cosimo23ORCID, Bergmann Christina45ORCID, Matucci-Cerinic Marco67ORCID, Launay David8ORCID, Riemekasten Gabriela9ORCID, Garzanova L10ORCID, Airò Paolo11ORCID, Rezus Elena1213ORCID, da Silva Jose A P1415ORCID, Del Galdo Francesco16ORCID, Hunzelmann Nicolas17, Chung Lorinda S18ORCID, Krasowska Dorota19ORCID, Distler Oliver2ORCID, van den Ende Cornelia H M1ORCID, Vonk Madelon C1ORCID, , Guiducci Serena, Walker Ulrich, Iannone Florenzo, Distler Oliver, Becvar Radim, Cutolo Maurizio, Rednic Simona, Allanore Yannick, Montecucco C, Inanc Murat, Carreira Patricia E, Czirják László, Iudici Michele, Kotyla Przemyslaw, Zanatta Elisabetta, Perdan-Pirkmajer Katja, Moroncini Gianluca, Airò Paolo, Balbir-Gurman Alexandra, Hunzelmann Nicolas, Idolazzi Luca, Mitrovic Josko, Denton Christopher, Vonk Madelon, Colic Jelena, Henes Jörg, Foeldvari Ivan, da Silva José António Pereira, Stamenkovic Bojana, De Santis Maria, Ananieva Lidia P, Müller-Ladner Ulf, Szücs Gabriella, Launay David, Riccieri Valeria, Balanescu Andra, Gheorghiu Ana Maria, Bergmann Christina, Mouthon Luc, Smith Vanessa, Cantatore Francesco Paolo, Mogensen Mette, Vanthuyne Marie, Alegre-Sancho Juan Jose, Anić Branimir, Cauli Alberto, Solanki Kamal, Rosato Edoardo, Foti Rosario, Maurer Britta, Senet Patricia, Chatelus Emmanuel, Litinsky Ira, Del Galdo Francesco, Castellví Ivan, Limonta Massimiliano, Marcoccia Antonella, Martin Thierry, Wojteczek Anna, Riemekasten Gabriela, Rezus Elena, Cuomo Giovanna, Epis Oscar Massimiliano, Sfikakis Petros, Furst Daniel, Ramazan Ana-Maria, de Vries-Bouwstra Jeska, Truchetet Marie-Elise, Lescoat Alain, Matucci-Cerinic Marco, Spierings Julia, Kuwana Masataka, Martin Mickaël, Simeón-Aznar Carmen-Pilar, Pârvu Magda, Boleto Gonçalo, Del Papa Nicoletta, Kastrati Kastriot, Selvi Enrico, Geroldinger-Simic Marija, Mosca Marta, Dzhus Marta, Karadag Duygu Temiz, Batalov Anastas, Ginosyan Knarik, Mukuchyan Vahan, Vardanyan Valentina, Haroyan Armine, Naffaa Mohammad, Maglio Cristina, Santos Cristiana Isabel Sieiro, Iwata Futoshi, Hinchcliff Monique, Cordeiro Ana, Giacomelli Roberto, Benvenuti Francesco, Rabaneda Esther Vicente, Györfi Andrea-Hermina, Nuñez Lilian Maria Lopez, De Angelis Rossella, Brigante Jorge Alejandro, Miedany Yasser, Zhang Lijun
Affiliation:
1. Department of Rheumatology, Radboud University Medical Center , Nijmegen, Netherlands 2. Department of Rheumatology, University Hospital Zurich, University of Zurich , Zurich, Switzerland 3. Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence—Careggi University Hospital , Florence, Italy 4. Department of Internal Medicine 3, Rheumatology and Clinical Immunology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen , Erlangen, Germany 5. Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen , Erlangen, Germany 6. University Vita Salute San Raffaele , Milano, Italy 7. Unit of Immunology, Rheumatology, Allergy and Rare Diseases, and Division of Clinical and Experimental Rheumatology, IRCCS San Raffaele Hospital , Milan, Italy 8. Département de Médecine Interne et d’Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), Univ. Lille, CHU Lille , Lille, France 9. Department of Rheumatology and Clinical Immunology, University of Medical Center Schleswig-Holstein, University Lübeck , Germany 10. VA Nasonova Research Institute of Rheumatology , Moscow, Russian Federation 11. UOC Reumatologia e Immunologia Clinica, ASST Spedali Civili di Brescia , Brescia, Italy 12. Department of Rheumatology, ‘Grigore T. Popa’ University of Medicine and Pharmacy, 16 Universitatii Street , Iasi, Romania 13. Clinical Rehabilitation Hospital , Iasi, Romania 14. Faculty of Medicine, University of Coimbra , Coimbra, Portugal 15. Department of Rheumatology, Centro Hospitalar e Universitário de Coimbra , Coimbra, Portugal 16. Leeds Raynaud's And Scleroderma Program, NIHR Biomedical Research Centre Leeds Institute Of Rheumatic And Musculoskeletal Medicine, University of Leeds , Leeds, UK 17. Department of Dermatology, University of Cologne , Köln, Germany 18. Department of Medicine & Dermatology, Division of Immunology & Rheumatology, Stanford University School of Medicine and Palo Alto VA Health Care System , Palo Alto, CA, USA 19. Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin , Lublin, Poland
Abstract
Abstract
Background
Hypothesizing that early treatment yields improved prognosis, we aimed to investigate how the timing of immunosuppressive treatment relates to interstitial lung disease (ILD) development and the course of pulmonary function in systemic sclerosis (SSc).
Methods
A cohort was created using data from the EUSTAR database and Nijmegen Systemic Sclerosis cohort, including adult patients who started their first immunosuppressive treatment (i.e. mycophenolate mofetil, methotrexate, cyclophosphamide, tocilizumab or rituximab) after SSc diagnosis, and no signs of ILD on high-resolution CT. ILD-free survival and the course of forced vital capacity (FVC) % predicted were assessed for up to 5 years’ follow-up comparing patients who started early (disease duration ≤3 years) vs late with immunosuppression.
Results
1052 patients met the eligibility criteria. The early treatment group (n = 547, 52%) showed a higher prevalence of male sex, diffuse cutaneous subtype (53.1% vs 36.5%), and anti-topoisomerase-I antibody (ATA, 51.1% vs 42.7%). Most patients were treated with methotrexate (60.1%), whereas only a few patients were treated with biologics (1.7%). The incidence of ILD was 46.6% after mean (s.d.) 3.6 (1.4) years; the hazards ratio for ILD in the early treatment group was 1.13 (95% CI: 0.93, 1.38) after adjustment for confounders. FVC % predicted trajectories were comparable between groups.
Conclusion
Our findings did not confirm a preventive role of early initiation of immunosuppressive therapy vs late initiation on ILD development. However, our findings should be interpreted with caution, considering the high inflammatory, ATA-positive enriched nature of the cohort, confounding by indication, and that very few patients were treated with biologics.
Funder
Foundation for Research in Rheumatology Gruppo Italiano Lotta alla Sclerodermia European Scleroderma Trials and Research Group Scleroderma Clinical Trials Consortium Scleroderma Research Foundation Wellcome Trust German Research Association German Scleroderma Foundation
Publisher
Oxford University Press (OUP)
|
|