Treatment-dependent biomarkers for worsening lung fibrosis
In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.
“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.
The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.
Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.
For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:
- Granulocyte-macrophage colony-stimulating factor
- Interleukin-1
- Monocyte chemoattractant protein–3
- Chemokine ligand–5
- Transforming growth factor–beta
- Hepatocyte growth factor
- Stem cell factor
- IL-4
- TGF-alpha
Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.
Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.
After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.
“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”
Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.
“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”
The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.
A version of this article first appeared on Medscape.com.