Emerging Therapeutic Options for Refractory Pulmonary Sarcoidosis: The Evidence and Proposed Mechanisms of Action

Abstract

Sarcoidosis is a systemic disease with heterogenous clinical phenotypes characterized by non-necrotizing granuloma formation in affected organs. Most disease either remits spontaneously or responds to corticosteroids and second-line disease-modifying therapies. These medications are associated with numerous toxicities that can significantly impact patient quality-of-life and often limit their long-term use. Additionally, a minority of patients experience chronic, progressive disease that proves refractory to standard treatments. To date, there are limited data to guide the selection of alternative third-line medications for these patients. This review will outline the pathobiological rationale behind current and emerging therapeutic agents for refractory or drug-intolerant sarcoidosis and summarize the existing clinical evidence in support of their use.

Keywords: fibrosis; granuloma; refractory; sarcoidosis; therapy.

Figure 1

Schematic for non-necrotizing granuloma formation in pulmonary sarcoidosis highlighting emerging therapeutic targets and medications. Abbreviations: CCL20—chemokine ligand 20; CXCL10—C-X-C ligand 10; CACL16—C-X-C ligand 16, GM-CSF—granulocyte-macrophage colony-stimulating factor, IFN-γ—interferon-gamma, IL—interleukin; IL6R—interleukin-6 receptor, JAK—janus kinase; mTOR—mammalian target of rapamycin; MCP-1—monocyte chemoattractant protein-1; NRP—neuropilin; TNFα—tumor necrosis factor-alpha. Created with BioRender.com.