Document Type
Article
Publication Date
4-11-2025
Original Citation
Gunes I,
Bernstein E,
Cowper S,
Panse G,
Pradhan N,
Camacho L,
Page N,
Bundschuh E,
Williams A,
Carns M,
Aren K,
Fantus S,
Volkmann E,
Bukiri H,
Correia C,
Kolachalama V,
Wilson F,
Mawe S,
Mahoney J,
Hinchcliff M.
Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis. Arthritis Res Ther. 2025;27(1):85.
Keywords
JMG, Humans, Female, Male, Middle Aged, Skin, Scleroderma, Systemic, Adult, Neural Networks, Computer, Biopsy, Treatment Outcome, rho-Associated Kinases
JAX Source
Arthritis Res Ther. 2025;27(1):85.
ISSN
1478-6362
PMID
40217251
DOI
https://doi.org/10.1186/s13075-025-03508-9
Grant
(JMM) 1R01GM141309
Abstract
BACKGROUND: The modified Rodnan skin score (mRSS), a measure of systemic sclerosis (SSc) skin thickness, is agnostic to inflammation and vasculopathy. Previously, we demonstrated the potential of neural network-based digital pathology applied to SSc skin biopsies as a quantitative outcome. Here, we leverage deep learning and histologic analyses of clinical trial biopsies to decipher SSc skin features 'seen' by artificial intelligence (AI).
METHODS: Adults with diffuse cutaneous SSc ≤ 6 years were enrolled in an open-label trial of belumosudil [a Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitor]. Participants underwent serial mRSS and arm biopsies at week (W) 0, 24 and 52. Two blinded dermatopathologists scored stained sections (e.g., Masson's trichrome, hematoxylin and eosin, CD3, α-smooth muscle actin) for 16 published SSc dermal pathological parameters. We applied our deep learning model to generate QIF signatures/biopsy and obtain 'Fibrosis Scores'. Associations between Fibrosis Score and mRSS (Spearman correlation), and between Fibrosis Score and mRSS versus histologic parameters [odds ratios (OR)], were determined.
RESULTS: Only ten patients were enrolled due to early study termination, and of those, five had available biopsies due to fixation issues. Median, interquartile range (IQR) for mRSS change (0-52 W) for the ten participants was -2 (-9-7.5) and for the five with biopsies was -2.5 (-11-7.5). The correlation between Fibrosis Score and mRSS was R = 0.3; p = 0.674. Per 1-unit mRSS change (0-52 W), histologic parameters with the greatest associated changes were (OR, 95% CI, p-value): telangiectasia (2.01, [(1.31-3.07], 0.001), perivascular CD3 + (0.99, [0.97-1.02], 0.015), and % of CD8 + among CD3 + (0.95, [0.89-1.01], 0.031). Likewise, per 1-unit Fibrosis Score change, parameters with greatest changes were (OR, p-value): hyalinized collagen (1.1, [1.04 - 1.16], < 0.001), subcutaneous (SC) fat loss (1.47, [1.19-1.81], < 0.001), thickened intima (1.21, [1.06-1.38], 0.005), and eccrine entrapment (1.14, [1-1.31], 0.046).
CONCLUSIONS: Belumosudil was associated with non-clinically meaningful mRSS improvement. The histologic features that significantly correlated with Fibrosis Score changes (e.g., hyalinized collagen, SC fat loss) were distinct from those associated with mRSS changes (e.g., telangiectasia and perivascular CD3 +). These data suggest that AI applied to SSc biopsies may be useful for quantifying pathologic features of SSc beyond skin thickness.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.