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Early ILD Progression in Systemic Sclerosis Linked to Higher Mortality, Not Continued Lung Decline: Study Suggests

Norway: A recent multicentre observational cohort study published in The Lancet Rheumatology offers new insights into disease progression patterns in patients with systemic sclerosis-associated interstitial lung disease (ILD). The study, led by Prof Anna-Maria Hoffmann-Vold of Oslo University Hospital, suggests that initial ILD progression does not necessarily indicate ongoing deterioration but is linked to increased mortality, highlighting the need for timely treatment in high-risk individuals.
Systemic sclerosis is a complex autoimmune condition that frequently affects the lungs, leading to ILD. Clinicians often initiate treatment once signs of ILD progression are observed. However, it remains unclear whether early progression predicts subsequent lung decline. This study aimed to clarify whether patients who experience an initial decline in lung function are at continued risk for further deterioration.
The researchers examined data from a prospectively followed cohort of 231 patients with systemic sclerosis-associated ILD, diagnosed between 2001 and 2019, and treated at Oslo University Hospital and the University Hospital Zurich. All participants met the 2013 ACR-EULAR classification criteria and were monitored annually for four years. An enriched validation cohort from the University of Michigan included an additional 121 patients with short disease duration.
The primary measure of ILD progression was a decline in forced vital capacity (FVC) of 5% or more between annual visits. Secondary definitions included FVC decline of 10% or more, progressive pulmonary fibrosis (PPF), and progressive fibrosing ILD (PF-ILD).
The findings were reported to be as follows:
- At the first follow-up, 31% of patients showed an FVC decline of at least 5%.
- Patients with this early FVC decline were less likely to experience further progression in the following year (OR 0.28).
- In the validation cohort, 34% of patients had early FVC decline, which also did not predict further deterioration (OR 0.22).
- Early FVC decline was associated with a higher risk of mortality (hazard ratio 1.66).
- Despite the limited risk of further lung decline, patients with initial progression faced an increased risk of death.
These findings challenge current clinical approaches that prioritize treatment only after observing progression. Instead, the study supports shifting towards earlier intervention, particularly in patients deemed at risk for progression based on other clinical markers. The authors emphasize the importance of identifying high-risk individuals early and initiating therapy before substantial lung damage occurs.
The authors concluded, "Further research is needed to validate these observations in larger, more diverse cohorts. However, the results already signal a potential change in the management of systemic sclerosis-associated ILD, with earlier treatment strategies likely to improve patient outcomes."
Reference:
Hoffmann-Vold AM, Petelytska L, Fretheim H, Aaløkken TM, Becker MO, Jenssen Bjørkekjær H, Brunborg C, Bruni C, Clarenbach C, Diep PP, Dobrota R, Durheim MT, Elhai M, Frauenfelder T, Huang S, Jordan S, Langballe E, Midtvedt Ø, Mihai C, Mulcaire-Jones E, Pugashetti JV, Sprecher M, Oldham J, Molberg Ø, Khanna D, Distler O. Predicting the risk of subsequent progression in patients with systemic sclerosis-associated interstitial lung disease with progression: a multicentre observational cohort study. Lancet Rheumatol. 2025 Jul;7(7):e463-e471. doi: 10.1016/S2665-9913(25)00026-8. Epub 2025 May 14. PMID: 40381640.
Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751