Cancer Association in Patients with Immune-Mediated Inflammatory Diseases: A Five-Year Nationwide Italian Cohort Study

<b>Background</b>: Cancer represents a major concern in rheumatology. Epidemiological studies have demonstrated associations between rheumatic conditions and increased cancer risk at specific sites. However, comprehensive Italian epidemiological data on this association remain lacking. <b>Methods:</b> We conducted a nationwide retrospective cohort study using Italian Hospital Discharge Records from patients hospitalized between 1 January and 31 December 2018, with follow-up until 31 December 2023. Adult patients with Immune-mediated inflammatory diseases (IMID), including rheumatoid arthritis (RA) and diffuse diseases of connective tissue (DDCT), were the exposed group. The unexposed group included patients with primary diagnoses of injury and poisoning, with no IMID history. We used multivariable logistic regression models to assess cancer association, adjusting for demographics, geography, time of follow-up and comorbidities. <b>Results:</b> We included 54,896 IMID patients (exposed) and 301,126 unexposed. During the five-year follow-up, the IMID group was significantly associated with cancer (adjusted OR 1.32, 95% CI 1.27-1.38; <i>p</i> < 0.001). The OR_adj decreased over time, from 1.83 (<i>p</i> < 0.001) in year one to 1.20 (<i>p</i> < 0.001) from the fifth year onward. Significant association with lung cancer (OR_adj 1.74; <i>p</i> < 0.001), leukemia and lymphoma (OR_adj 1.98; <i>p</i> < 0.001), bladder (OR_adj 1.48; <i>p</i> < 0.001) and melanoma (OR_adj 1.48; <i>p</i> = 0.009) were observed in the IMID group. DDCT patients showed an overall higher cancer risk (OR_adj 1.53, <i>p</i> < 0.001) than RA patients (OR_adj 1.20, <i>p</i> < 0.001). <b>Conclusions:</b> This first nationwide Italian study confirms an association with cancer in IMID patients, with the highest association in the first year post-diagnosis. The temporal decrease in cancer risk generates the hypothesis that inflammation, rather than medication, may be the primary driver. These findings support enhanced cancer surveillance in IMID patients, particularly during the first year after diagnosis.