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

Nature Reviews Rheumatology volume 19, page 676 (2023)Cite this article

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We thank the authors for their thoughtful letter regarding our Review article (Pope, J. E. et al. State-of-the-art evidence in the treatment of systemic sclerosis. Nat. Rev. Rheumatol. 19, 212–226 (2023))1, as they raise some interesting points (Andréasson, K. et al. Is classifying SSc-ILD drugs as either immunosuppressive or anti-fibrotic misleading? Nat. Rev. Rheumatol. https://doi.org/10.1038/s41584-023-01013-4 (2023))2. We agree that it is simplistic to categorize drugs as either immunosuppressant (anti-inflammatory) or anti-fibrotic when considering the treatment of interstitial lung disease (ILD) and pulmonary fibrosis in systemic sclerosis (SSc) and also when considering the complex nature of SSc in other organs, such as pulmonary arterial hypertension (PAH) and skin disease. For instance, mycophenolate mofetil (MMF) is described as a strong immunosuppressive, but it also has anti-proliferative and anti-fibrotic effects3. Other important work demonstrates that fibrosis and inflammation co-occur in fibrotic lungs and can alter and/or upregulate each other’s processes4.

Janus kinase (JAK) inhibitors might have beneficial effects in SSc and ILD, although randomized controlled trials need to be performed. In vitro, JAK inhibitors affect M1 macrophages, which are mainly pro-inflammatory, and profibrotic M2 macrophages. Inhibition of JAK signalling has important anti-inflammatory effects, with reduced expression of certain markers (CD86, MHCII and TLR4) in M1 macrophages and reduced secretion of markers of M2a activation (CD206 and CCL18), which suggests that immunosuppressive effects can occur in conjunction with less-studied anti-fibrotic actions5.

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References

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Authors and Affiliations

  1. Division of Rheumatology, St Joseph’s Health Care, London, Ontario, Canada

    Janet E. Pope

  2. Department of Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada

    Janet E. Pope

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  1. Janet E. Pope
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Correspondence to Janet E. Pope.

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Competing interests

J.E.P. declares that she has research grants from AbbVie, Bayer, BI, BMS, Frensenius Kabi, Lilly, Mallinckrodt Pharmaceuticals, Merck, Roche and Seattle Genetics; that she has consulted for AbbVie, Amgen, BI, BMS, Celltrion, EMERALD, Frensenius Kabi, Galapagos, Gilead, Janssen, Lilly, Mallinckrodt Pharmaceuticals, Medexus, Merck, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sandoz, Samsung, Sanofi, Sobi, Teva and Viatris; and that she has been a speaker or attended an advisory board for AbbVie, Amgen, BI, BMS, Frensenius Kabi, Galapagos, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Sandoz, Sanofi and UCB.

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Pope, J.E. Reply to: Is classifying SSc-ILD drugs as either immunosuppressive or anti-fibrotic misleading?. Nat Rev Rheumatol 19, 676 (2023). https://doi.org/10.1038/s41584-023-01014-3

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