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

## TL;DR

This Italian study finds that people with immune diseases have a higher cancer risk, especially in the first year after diagnosis, suggesting inflammation may be a key factor.

## Contribution

The study is the first nationwide Italian analysis of cancer risk in immune-mediated inflammatory diseases with five-year follow-up and broader inclusion criteria.

## Key findings

- IMID patients had a significantly higher cancer risk (adjusted OR 1.32) compared to unexposed patients.
- Cancer risk was highest immediately after IMID diagnosis and decreased over time, suggesting inflammation-driven mechanisms.
- Diffuse diseases of connective tissue showed higher cancer risk than rheumatoid arthritis.

## Abstract

This study provides the first nationwide Italian evidence on cancer risk in Immune-mediated inflammatory diseases (IMID) encompassing 356,022 patients with five-year follow-up. Our broader inclusion criteria beyond traditional rheumatoid arthritis populations provide insights into diverse connective tissue conditions. We found that association with cancer onset is highest immediately after IMID diagnosis; the temporal decline in cancer risk over subsequent years supports the hypothesis of inflammation-driven rather than treatment-related mechanisms, reinforcing the potential protective effects of early anti-inflammatory therapy. The consistent findings across international populations suggest that enhanced cancer surveillance protocols should be implemented for IMID patients, particularly during the first year after diagnosis. The temporal pattern of risk reduction supports early anti-inflammatory treatment strategies. Future research should focus on identifying specific inflammatory biomarkers that predict cancer risk.

Background: 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. Methods: 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. Results: 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; p < 0.001). The ORadj decreased over time, from 1.83 (p < 0.001) in year one to 1.20 (p < 0.001) from the fifth year onward. Significant association with lung cancer (ORadj 1.74; p < 0.001), leukemia and lymphoma (ORadj 1.98; p < 0.001), bladder (ORadj 1.48; p < 0.001) and melanoma (ORadj 1.48; p = 0.009) were observed in the IMID group. DDCT patients showed an overall higher cancer risk (ORadj 1.53, p < 0.001) than RA patients (ORadj 1.20, p < 0.001). Conclusions: 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.