Abstract

Background:An increased incidence of cancer in patients with systemic sclerosis (SSc) is well-established1. Current knowledge about the onco-transforming power of immunosuppressive treatments in both non-rheumatological and rheumatological pathologies, suggests an increased incidence of hematological and solid neoplasms2. Evidences on the possible role of the immunosuppressants in the onset of cancer during SSc are lacking.Objectives:To evaluate the incidence of malignancies in SSc patients exposed to immunosuppressive therapy.Methods:The incidence of neoplasia in a cohort of 600 patients with SSc was evaluated retrospectively. Patients diagnosed with malignancy within 36 months from SSc onset were excluded from the analysis since suspected for paraneoplastic form. Patients exposed to methotrexate, cyclophosphamide, azathioprine and mycophenolate were confronted with a group comparable for age at onset, sex, disease variant, autoantibodies and exposure to other disease-specific therapies, using propensity score matching analysis. The considered follow-up was between the clinical onset and the diagnosis of cancer or the last available visit or the twenty-fifth year of illness.Results:The analysis was carried out on 526 patients observed for an average period of 12.1 ± 6.0 years (males 9.5%, age at onset 49.0 ± 15.3 years); 24.9% had diffuse cutaneous variant of the disease and 39.0% and 34.8% were respectively positive for anti-centromere and anti-Scl70 antibodies. During the follow-up, 19.0% of patients were exposed to cyclophosphamide, 15.3% to azathioprine, 14.4% to methotrexate and 11.6% to mycophenolate mofetil. Sixty-five cancer diagnoses were made after the 36th month from onset (incidence 1.02: 100 patients/year), comprising 16 mammary cancers, 12 cancers of the gastro-intestinal tract, 11 cancers of the head-neck area, 10 cancers of the lungs, 9 cases of skin-cancer, 5 haematological malignancies and 1 brain tumour. The incidence of cancers did not differ in relation to treatment with cyclophosphamide (X2 = 0.001, p = 0.961), azathioprine (X2 = 2.141, p = 0.143), mycophenolate mofetil (X2 = 0.001, p = 0.993) or methotrexate (X2 = 0.920, p = 0.337) (Figure 1).Conclusion:Our data are consistent with an increased incidence of neoplasms in the course of SSc, with a rate that appears almost doubled compared to the general Italian population with similar sex and age distribution (0.55: 100 patients/year; Italian Association of Tumor Registries data3). In our SSc cohort this risk is independent of exposure to immunosuppressive drugs commonly used for the treatment of scleroderma disease.

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