Abstract
Tumour necrosis factor-alpha (TNF-α) is a pivotal proinflammatory cytokine involved in the pathogenesis of numerous immune-mediated inflammatory diseases. While physiological levels are essential for host defence and tissue homeostasis, dysregulated TNF-α production leads to persistent inflammation and tissue damage. TNF inhibitors (TNFi) have transformed the management of inflammatory arthritides; however, their therapeutic scope has expanded beyond traditional indications. This narrative review critically examines the evolving role of TNF-α inhibitors in the management of inflammatory and autoimmune diseases beyond arthritis. A narrative review of published literature was performed, focusing on clinical trials, observational studies and real-world evidence assessing the efficacy and safety of TNFi in non-arthritic conditions. TNFi, including monoclonal antibodies (infliximab, adalimumab, golimumab, certolizumab pegol) and the receptor fusion protein etanercept, have demonstrated significant efficacy in a wide spectrum of diseases such as inflammatory bowel disease, uveitis and hidradenitis suppurativa. Their use is particularly valuable in patients who are refractory or intolerant to conventional therapies. Differences in molecular structure and mechanism of action among TNFi may influence clinical response across disease phenotypes. Despite increasing use, several indications remain off-label and long-term safety data in certain conditions are limited. TNFi represent a versatile and effective therapeutic strategy across diverse immune-mediated diseases beyond arthritis. Further well-designed studies are needed to better define their role in emerging indications and to optimise individualised treatment approaches.