| Sumario: | Simple Summary: Biologic therapies have revolutionised the treatment of chronic inflammatory diseases such as psoriasis, arthritis, and asthma. However, their immunosuppressive effects have led to concerns about the risk of cancer promotion in patients with prior or active cancer illness. Reassurance for patients and prescribers is compounded by the exclusion of patients with cancer from pivotal clinical trials of these agents. This review collates large-scale health databases and real-world evidence to better understand these risks. These available data demonstrate that biologic agents can be used with caution in certain patients with a history of malignancy following multidisciplinary discussion; however, in those with active malignancy there is limited evidence. The majority of evidence is heterogenous and excludes patients with a history of malignancy. Such information is crucial for helping doctors and patients make informed decisions about treatment. Greater reassurance would be possible with more long-term follow-up and greater use of inclusive, patient co-created real-world registries which leverage developing artificial intelligence tools to monitor more diverse patient populations. The rapid expansion of biologic therapies for immune-mediated inflammatory diseases has raised significant clinical concerns regarding malignancy risk, particularly for patients with a history of cancer. This narrative review explores the safety of targeted therapies across dermatology, rheumatology, respiratory medicine, and gastroenterology to guide clinicians in these therapeutic dilemmas. We conducted a non-systematic review of the literature, prioritising longitudinal registry and real-world cohort data over clinical trials to better capture malignancy outcomes with long latency periods. Results indicate that tumour necrosis factor (TNF) inhibitors, which have the most extensive evidence base, do not consistently demonstrate an increased risk of overall incident malignancy or recurrence across specialties. Newer agents, including interleukin (IL)-17 and IL-23 inhibitors, show reassuring safety profiles in both trial and registry data. While dupilumab is associated with the potential diagnostic 'unmasking' of pre-existing cutaneous T-cell lymphoma, overall cancer rates remain stable among users. Most clinical guidelines support an individualised, multidisciplinary approach involving oncology consultation. We conclude that biologic agents can be used cautiously in certain patients with a history of malignancy following multidisciplinary discussion; however, in those with active malignancy there are no meaningful data that exist. Most evidence is heterogenous and excludes patients with a history of malignancy. Future management requires validated decision frameworks and mandatory participation in real-world patient co-created registries which leverage developing artificial intelligence tools to refine long-term safety assessments.
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