AB1175 RISK OF CANCER IN PATIENTS WITH SYSTEMIC SCLEROSIS IS INFLUENCED BY SERUM AUTOANTIBODIES, CUTANEOUS PHENOTYPE, AND IMMUNOSUPPRESSIVE THERAPIES
Authors: M. De Santis, A. Tonutti, F. Motta, A. Ceribelli, N. Isailovic, R. Ragusa, C. Selmi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic sclerosis (SSc) is linked to an increased risk of cancer, and cancer-associated SSc is defined when occurring within three years of the detected malignancy. Predictors of cancer are poorly elucidated with clinical features, serum autoantibodies, and exposure to immunosuppressants proposed as candidates. <h3>Objectives:</h3> To investigate the clinical, serological, and therapeutic characteristics associated with the prevalence of cancer overall and cancer-associated SSc. <h3>Methods:</h3> In this retrospective cohort study, we analyzed the clinical features, including therapies, and the serum autoantibody profile obtained with RNA- and protein-immunoprecipitation, Western-blot, immunoblot, and ELISA. Patients negative for anticentromere (ACA), anti-Scl-70, and anti-RNA polymerase III (RNAP3) were defined <i>CTP-negative</i>. <h3>Results:</h3> A total of 290 patients with SSc (followed for a total of 5,370 patient-years) were included, with a mean age of 54 ± 16 years, 7% males, 25% with smoking history; 15% had diffuse SSc (dcSSc), 33% interstitial lung disease, 13% primary heart involvement, and 12% increased pulmonary arterial pressure. Autoantibody distribution was as follows: 56% ACA, 23% anti-Scl-70, and 9% anti-RNAP3. A diagnosis of cancer was made in 59 (20%) subjects, while cancer-associated SSc was observed in 23 (8%) cases. Both overall cancer and cancer-associated SSc were more frequent in patients who were older at the time of diagnosis and with anti-Ro52 or U3-RNP (<b>Table 1</b>). Combining clinical manifestations and autoantibodies, CTP-negative patients with dcSSc had a higher prevalence of cancer-associated SSc, as well as overall cancers. In the analysis of immunosuppressants, 13 patients in which cancer preceded SSc were excluded. The overall exposure to immunosuppressants was not associated with cancer occurrence. Fifty patients were on mycophenolate mofetil (MMF) treatment at the time of this analysis (median dosage 2 g/d – IQR 1.5-3; median duration 36 months – IQR 15-57): lower cancer prevalence was noted among patients on MMF (3/50, 6%) compared to counterparts not receiving any immunosuppressant [41/221, 19%; p = 0.030; OR 0.28, 95% CI (0.05-0.94)]. The most common cancers originated from the breast [22/59 (37%)], lung [8/59 (14%)], or were hematologic [7/59 (12%)] malignancies. Older age, anti-Ro52, and CTP-negative status (especially in dcSSc) were observed more frequently in patients with breast cancer compared to cancer-negative SSc. Lung cancer was associated with older age, male sex, dcSSc, increased pulmonary arterial pressure, anti-Th/To, and U3-RNP, but not with interstitial lung disease. Hematologic malignancies were associated with a higher prevalence of anti-U3-RNP. <h3>Conclusion:</h3> We propose factors to be considered to stratify patients with SSc into different subsets according to cancer risk and maximize the efficacy of screening programs. Of note, we confirm the role of the CTP-negative status, and propose for the first time that rarer autoantibodies are associated with cancer in SSc. <h3>REFERENCES:</h3> <b>NIL.</b> <b>Table 1.</b> Demographic, clinical, and serological features of patients with SSc without cancer, overall cancers, and cancer-associated SSc. <b>Table 2.</b> Demographic, clinical, and serological features of patients with SSc according to different types of cancer, compared with the cancer-negative SSc counterpart. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Maria De Santis: None declared, Antonio Tonutti: None declared, Francesca Motta: None declared, Angela Ceribelli: None declared, Natasa Isailovic: None declared, Rita Ragusa: None declared, Carlo Selmi AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA Pharma - Recordati, Galapagos, Janssen, Novartis, Octapharma, Pfizer, Recordati Rare Disease, SOBI, AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA Pharma - Recordati, Galapagos, Janssen, Novartis, Octapharma, Pfizer, Recordati Rare Disease, SOBI, AbbVie, Amgen, Janssen, Novartis, Pfizer.