medwireNews: An observational cohort study suggests that interstitial lung disease (ILD) progression in patients with systemic sclerosis does not necessarily predict future progression.
“These findings have implications for clinical practice because they do not lend support to the current practice of waiting for progression before initiating or escalating treatment in patients with systemic sclerosis-associated ILD,” say the authors.
Writing in The Lancet Rheumatology, Anna-Maria Hoffmann-Vold, from Oslo University Hospital in Norway, and colleagues analyzed data from 231 adults (mean age 48 years; 76% women) with systemic sclerosis-associated ILD. The participants were recruited at two specialist centers in Norway and Switzerland and followed up annually over 4 years.
The participants had a mean systemic sclerosis disease duration of 10.4 years, and a mean forced vital capacity (FVC) percent predicted of 89%.
To validate their findings, the researchers also included an enriched cohort of 121 patients (mean age 52 years, 69% women) with a short systemic sclerosis disease duration of up to 3 years – a known risk factor for progressive ILD – comprising 68 from the original cohort and a further 53 from the USA.
Between visits 1 and 2 (first 12 months), 71 (31%) patients in the main cohort experienced ILD progression, based on a primary definition of an absolute decline in FVC of at least 5%. However, only 20% of these individuals had further progression at visit 3, 12 months later, compared with 31% of 160 patients who had not initially progressed.
A similar pattern was seen when different definitions for ILD progression were used, including an FVC decline of 10% or more, and the presence of progressive pulmonary fibrosis or progressive fibrosing ILD, with corresponding rates of further ILD progression at visit 3 of 12%, 16%, and 27%.
“Irrespective of definition, we did not find that ILD progression was a risk factor for subsequent [ILD] progression,” the authors report. They caution that this may lead to a “risk of over-treating some patients displaying recent short-term lung function decline, while under-treating those who appear stable but progress after a longer period of stability.”
Indeed, the team found that “ILD progression from visit 1 to visit 2 reduced the risk for further progression from visit 2 to visit 3,” with multivariable analysis showing a 72% reduction in the risk for subsequent progression. A similar pattern was also observed in the enriched cohort, where the likelihood of further progression fell by 78%.
Hoffmann-Vold and colleagues note that even though ILD progression did not predict future ILD progression, it was associated with mortality. Just a single FVC decline of 5% or more was associated with a 66% higher risk for death compared with no progression. Over the median follow-up of 9.8 years, 35% of the patients in the main cohort died, with declining survival rates of 93%, 83%, and 76% at 1, 3, and 5 years, respectively.
The study also showed that treatment changes following progression did not explain the reduced likelihood of subsequent progression. Although a higher proportion of patients with progression initiated new immunosuppressive therapy, this difference was not statistically significant. Moreover, even after excluding those who changed treatment, the authors found that ILD progression from visit 1 to visit 2 reduced the risk for further ILD progression by 69%.
The authors point out several study limitations, such as the inclusion of only those patients with consecutive lung function assessments, potentially enriching the cohort for more progressive ILD, and primarily White participants, limiting generalizability to other ethnic groups.
In a linked commentary, Kathleen Morrisroe (St Vincent’s Hospital, Melbourne, Victoria, Australia) and Murray Barron (McGill University, Montreal, Quebec, Canada) write that the study “highlights our inability to identify those at risk of systemic sclerosis-associated ILD progression.”
They suggest a need “to look beyond the patient phenotype at external factors such as environmental influences […] or other geographical and occupational factors.”
The commentators add: “If such risk factors are identified, a clinically useful and sorely needed risk stratification tool could be developed to help identify patients for whom therapeutic intervention is warranted and the best timing of that intervention.”
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Lancet Rheumatol 2025: doi:10.1016/S2665-9913(25)00026-8
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