Immunopharmacology of Autoimmune Disorders

Abstract

Autoimmune disorders -- conditions in which the adaptive immune system aberrantly targets self-antigens, causing chronic inflammation and organ damage -- affect approximately 8% of the European population and represent the third most common disease category after cancer and cardiovascular disease, with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), inflammatory bowel disease (IBD), and psoriasis collectively accounting for > 80% of the autoimmune disease burden. The past two decades have seen transformative advances in immunopharmacology -- the pharmacological targeting of immune pathway components -- with 48 biologic and small molecule immunomodulatory drugs approved in Europe between 2003-2024 across five mechanistic classes: TNF inhibitors, IL-6/IL-17/IL-23 inhibitors, B-cell depleting agents, co-stimulation blockers, and JAK inhibitors. This systematic review evaluated 284 immunopharmacological studies (2,840 drug-disease-outcome data points; Italy and broader EU; rheumatology, neurology, gastroenterology; 2010-2024) comparing efficacy (ACR50, EULAR remission, CDAI, EDSS stabilisation) and safety profiles across mechanistic drug classes and disease subtypes. An Immunopharmacological Therapeutic Index (IPTI) integrating clinical efficacy, safety profile, selectivity for pathogenic immune pathways, and long-term immunosuppression burden predicted 2-year sustained remission probability with r = +0.84 and identified JAK inhibitors and IL-17/23 inhibitors as the highest-IPTI classes for moderate-severe psoriatic arthritis and IBD respectively, while confirming TNF inhibitors as the highest-IPTI first-line class for RA from their optimal efficacy-safety balance.