Publications

Therapeutics used to manage chronic diseases-rheumatologic, metabolic, cardiovascular, infectious, and oncologic-carry diverse immunological risks that can undermine patient safety and long-term outcomes. Immunotoxicity encompasses immunosuppression and infection risk, hypersensitivity and allergic reactions, immune-mediated organ damage (autoimmunity), hematologic immune injury, and aberrant inflammatory responses such as cytokine release syndrome. Mechanisms range from direct cytotoxic effects on immune cells and off-target kinase inhibition to immunogenicity of biologic agents, Fc-mediated complement activation, formation of drug-protein haptens, and dysregulation of immune checkpoints. This review synthesizes mechanistic pathways, illustrates representative classes of therapeutics (conventional immunosuppressants, biologic DMARDs and monoclonal antibodies, small-molecule kinase inhibitors, hormone and metabolic therapies, and advanced cellular therapies), and describes common clinical phenotypes. It then outlines risk factors, pre-treatment assessment, monitoring strategies, and management approaches to mitigate harm, including screening for latent infections, vaccination strategies, therapeutic drug monitoring, and stewardship of immunomodulatory regimens. Finally, it highlights gaps in preclinical immunotoxicity testing, the role of pharmacogenomics, and priorities for future research and regulatory harmonization. Clinicians and drug developers must integrate mechanistic understanding with patient-centred monitoring to balance therapeutic benefit against immunologic risk.