Systemic Sclerosis-Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration-Approved Therapies in Clinical Practice

Dinesh Khanna, Alain Lescoat, David Roofeh, Elana J Bernstein, Ella A Kazerooni, Michael D Roth, Fernando Martinez, Kevin R Flaherty, Christopher P Denton, Dinesh Khanna, Alain Lescoat, David Roofeh, Elana J Bernstein, Ella A Kazerooni, Michael D Roth, Fernando Martinez, Kevin R Flaherty, Christopher P Denton

Abstract

Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases, and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the US Food and Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-associated ILD (SSc-ILD): nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, 2 generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy for the management of SSc-ILD is still to be determined. The objectives of this review are 2-fold: 1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and 2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical versus clinical ILD) and associated risk of progression (low versus high risk). The pharmacologic and nonpharmacologic options for first- and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD.

© 2021, American College of Rheumatology.

Figures

Figure 1:. HRCT images of three different…
Figure 1:. HRCT images of three different patients with SSc-interstitial lung disease.
Nonspecific interstitial pneumonitis (NSIP) with a lower lobe subpleural predominant distribution of primarily ground glass opacity (* and circles) (A). Definite usual interstitial pneumonitis (UIP) with subpleural lower lobe honeycombing (arrows) (B). Mild interstitial lung disease on the supine image (arrows) (C) which could be interpreted as dependent atelectasis, however it persists on the prone image (D), confirming the presence of interstitial lung disease; the pattern of septal thickening (arrows) and ground glass opacity (*) without bronchiectasis is most consistent with NSIP in a patient with scleroderma.
Figure 2:
Figure 2:
Conceptual framework for the management of SSc-ILD
Figure 3:
Figure 3:
Expert opinion on the management of SSc-ILD

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