Preventive effects of early immunosuppressive treatment on the development of interstitial lung disease in systemic sclerosis
Authors: Velauthapillai Arthiha , Bootsma M F R , Bruni Cosimo , Bergmann Christina , Matucci-Cerinic Marco , Launay David , Riemekasten Gabriela , Garzanova L , Airò Paolo , Rezus Elena , da Silva Jose A P , Del Galdo Francesco , Hunzelmann Nicolas , Chung Lorinda S , Krasowska Dorota , Distler Oliver , van den Ende Cornelia H M , Vonk Madelon C ,   EUSTAR Collaborators, 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 
Published: July 2024

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.