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Is classifying SSc-ILD drugs as either immunosuppressive or anti-fibrotic misleading?

Nature Reviews Rheumatology volume 19, page 675 (2023)Cite this article

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We read with great interest the comprehensive Review article by Pope et al. on the treatment of systemic sclerosis (SSc) (Pope, J. E. et al. State-of-the-art evidence in the treatment of systemic sclerosis. Nat. Rev. Rheumatol. 19, 212–226 (2023))1. We agree with the authors that results from cohort studies and randomized, placebo-controlled trials support the usage of several treatment strategies for SSc-interstitial lung disease (ILD), including drugs traditionally labelled as immunosuppressive, such as mycophenolate mofetil (MMF), and drugs originally approved for the treatment of fibrotic pulmonary disorders, such as nintedanib. However, we are concerned that categorizing currently available drugs as either ‘immunosuppressive’ or ‘anti-fibrotic’ is misleading1.

Fibrosis and immune activation are broad terms that encompass a wide range of integrated physiological and pathological processes. This holds true also for ILD, in which fibrosis (that is, an imbalance of extracellular matrix (ECM) turnover) develops in conjunction with inflammation2. For example, inflammatory cells that infiltrate the ECM can modulate the biological properties of the tissue interstitium through the release of matrix metalloproteases that degrade structural proteins into smaller fragments that express neoepitopes. These fragments have an altered function relative to that of their original protein, such as chemotactic properties that promote the further infiltration of inflammatory cells3.

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Authors and Affiliations

  1. Section of Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden

    Kristofer Andréasson & Viggo Hamberg

  2. Lung Biology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden

    Jenny Wigén & Gunilla Westergren-Thorsson

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  1. Kristofer Andréasson
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  2. Viggo Hamberg
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  3. Jenny Wigén
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  4. Gunilla Westergren-Thorsson
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Correspondence to Kristofer Andréasson.

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Andréasson, K., Hamberg, V., Wigén, J. et al. Is classifying SSc-ILD drugs as either immunosuppressive or anti-fibrotic misleading?. Nat Rev Rheumatol 19, 675 (2023). https://doi.org/10.1038/s41584-023-01013-4

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