Targeting cytokine pathways: the role of biologics in autoinflammatory disorders – Research

Introduction:

Autoinflammatory diseases are inherited disorders of innate immunity broadly classified into inflammasomopathies, interferonopathies, and complement-mediated disorders. These diseases are characterized by dysregulated cytokine signaling – particularly IL-1, IL-6, TNF, type I interferon, and JAK – STAT – managed through molecular targeted therapies. Prototypical entities include familial Mediterranean fever (FMF), TNF receptor – associated periodic syndrome (TRAPS), and cryopyrin-associated periodic syndromes (CAPS). Other conditions – notably mevalonate kinase deficiency (MKD/HIDS), deficiency of adenosine deaminase 2 (DADA2), haploinsufficiency of A20 (HA20), OTULIN-related autoinflammatory syndromes, and proteasome-associated autoinflammatory syndromes (PRAAS) – are increasingly recognized as responsive to biologic therapy.

Areas covered:

This review summarizes molecular mechanisms and therapeutic strategies, focusing on IL-1 blockade with anakinra, canakinumab, and rilonacept, as well as IL-6 and TNF inhibitors. Evidence from clinical trials and real-world studies is integrated, with attention to disease-specific efficacy, dosing, and safety.

Expert opinion:

IL-1 inhibition has revolutionized treatment of inflammasome-mediated diseases, enabling glucocorticoid-free remission and reducing amyloidosis risk. TNF inhibitors remain the standard for vasculopathic disorders such as DADA2, while IL-6 blockade and JAK inhibitors are useful in selected refractory cases. Recognition of novel syndromes such as HA20, OTULIN deficiency, and PRAAS has expanded the therapeutic landscape. Next-generation biologics targeting multiple cytokine pathways may further personalize therapy.