Tumor safety of biologic agents and targeted therapies in immune-mediated inflammatory arthritides

Immune-mediated inflammatory arthritides (IMIA), including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis, are chronic immune-driven disorders in which long-term malignancy safety has become a key determinant of therapeutic decision-making. Patients with IMIA are not oncologically neutral at baseline; persistent inflammatory burden, smoking exposure, age, and cumulative immunosuppressive treatment all modify cancer susceptibility. Against this background, biologic and targeted synthetic disease-modifying antirheumatic drugs may both reduce inflammation-associated oncogenic pressure and attenuate antitumor immune surveillance. In this narrative review, we synthesize current evidence on tumor safety across major biologic classes and Janus kinase inhibitors, with emphasis on data emerging through early 2026. Overall, most biologic therapies appear broadly reassuring with respect to overall malignancy, although non-melanoma skin cancer remains the most reproducible treatment-associated signal, particularly with tumor necrosis factor inhibitors and possibly abatacept. Rituximab retains a favorable profile in patients with prior lymphoproliferative disease, whereas IL-6 and IL-17/23 pathway inhibitors appear largely neutral or reassuring in currently available datasets. By contrast, JAK inhibitors require greater caution in risk-enriched rheumatoid arthritis populations, especially older patients, smokers, and those with prior malignancy or prolonged treatment exposure. Recent register-based studies have shown that overall cancer incidence with JAK inhibitors is comparable to that with TNF inhibitors, although lung and keratinocyte cancers occur more frequently in certain risk groups; accordingly, updated 2025 EULAR guidance recommends early initiation of targeted therapy after cancer remission and tailoring drug choice to prior cancer type and patient-specific factors. We further examine tumor-type-specific patterns, major modifiers of risk, and practical risk-stratified management strategies. The central clinical message is that malignancy safety in IMIA should be interpreted through an individualized framework that balances inflammatory control against oncologic vulnerability rather than through uniform class-based avoidance.