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

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.

YouTube as a source of information on systemic sclerosis

“…Systemic sclerosis, also called scleroderma, is an immune‐mediated rheumatic disease that has a higher mortality and morbidity compared to other rheumatic diseases 1 . Patients present with skin changes like skin thickening and swollen fingers, musculoskeletal pain and constitutional manifestations such as fatigue 2 .…”

“…In systemic sclerosis, the treatment of disease‐causing mechanisms such as immune activation, inflammation, vascular disease, and fibrosis is the target, while the treatment of complications related to organ involvement such as pulmonary hypertension, gastroesophageal reflux or renal crisis is another approach 5 . Nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the biologic agent targeting interleukin‐6 pathway) have now been approved by the Food and Drug Administration (FDA) and are indicated to slow the rate of decline in pulmonary function in patients with interstitial lung disease 1 …”

“…5 Nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the biologic agent targeting interleukin-6 pathway) have now been approved by the Food and Drug Administration (FDA) and are indicated to slow the rate of decline in pulmonary function in patients with interstitial lung disease. 1 In recent years, YouTube has become a popular source of health information; it has shown that 80% of Internet users access health information online. 6 The fact that YouTube videos are easily accessible and free of charge is one of the most important reasons for its popularity.…”

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses

“…In March 2021, the FDA also approved tocilizumab, an anti-IL-6 receptor humanized monoclonal antibody that blocks IL-6 signaling, for the same indication [8]. Nevertheless, evidencebased guidance on what drug class or individual agent would be optimal as a first-line preference, how to deal with situations in which only weak evidence supports one drug versus another and how to switch to alternate treatment options especially in patients with progressive fibrosing ILDs remains inconclusive [9][10][11][12][13]. The conflicting treatment algorithms [9][10][11][12][13] reflect the variability in management approaches for patients with CTD-ILDs across rheumatologists [14,15].…”

“…Nevertheless, evidencebased guidance on what drug class or individual agent would be optimal as a first-line preference, how to deal with situations in which only weak evidence supports one drug versus another and how to switch to alternate treatment options especially in patients with progressive fibrosing ILDs remains inconclusive [9][10][11][12][13]. The conflicting treatment algorithms [9][10][11][12][13] reflect the variability in management approaches for patients with CTD-ILDs across rheumatologists [14,15]. In routine clinical practice, physicians must balance a high level of need for treatment in a complex patient group with a potentially progressive disease phenotype against the possibility for adverse events from toxic therapies.…”