Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Abstract

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

Keywords: COVID-19; TNF-α; TNF-α inhibitors; biomarker; biosimilar agents; inflammation; monoclonal antibody.

Figure 1

Signaling pathways of TNF-α.

Figure 2

Timeline of the approval of TNF-α blockers in autoimmune diseases. AR, rheumatoid arthritis; CD, Crohn’s disease; AS, ankylosing spondylitis; PsA, psoriatic arthritis; PS, psoriasis; UC, ulcerative colitis; NIU, non-infectious uveitis; JIA, juvenile idiopathic arthritis.