Author:
Andreu-Suárez Á.,Serrano Warleta M.,De la Puente Bujidos C.
Abstract
BackgroundCyclophosphamide (CYC) is one of the first-line drugs for some serious manifestations of autoimmune diseases [1]. It has been associated with the appearance of a secondary cancer [2]. Several studies showing a higher incidence of cancer in small-vessel vasculitis in relation to CYC treatment have been carried out [3], but there is not much evidence about this complication in other autoimmune diseases.Objectives-Estimating the incidence of cancer in patients treated with CYC for serious manifestations of autoimmune diseases.-Comparing the incidence of cancer in autoimmune diseases treated with immunosuppressants (IS) against the incidence of cancer in the general population.MethodsThis is a single-center retrospective cohort study. We included patients over 18 years old assessed in outpatient clinics of the Rheumatology service at the Ramón y Cajal Hospital from 1990 to 2018. They had been diagnosed with: diffuse or limited cutaneous systemic sclerosis (dcSSc/LSScl), systemic lupus erythematosus (SLE), vasculitis or others. We divided the patients into two groups; those exposed to CYC throughout the follow-up and those not exposed to it (being treated with other IS). Patients who had an active cancer at the time of starting the immunosuppressive therapy were excluded.A descriptive analysis was carried out. The incidence of cancer was compared to the incidence of cancer in the general population according to the 2020 Spanish Network of Cancer Registries data. A multivariate analysis was subsequently performed.ResultsRegarding the baseline characteristics of the patients included, there were no significant statistical differences in the sex, median age, and personal history of cancer. There was a bigger percentage of smokers in the non-exposed group.The incidence of cancer was similar y both groups (7.5% vs. 4.1%; p0.211). The cumulative incidence of cancer in our sample was 55.55/1.000 patients (95% CI 32.1-94.6). The standardized incidence ratio was 2.19 (95% CI 3.30-11.92) and it was stratified by sex and age.The bivariate analysis is shown in Table 1.Table 1.Comparison between patients with or without appearance of cancer during the follow-up.Cancer (n 12)No cancer (n 204)P valueMale sex7 (58,33%)31 (15,19%)0,001Age at the time of the study69,92 (±7,54)53,88 (±16,75)0,001Smoking habit6 (50%)45 (22,06%)0,027Personal history of cancer5 (41,66%)5 (2,45%)<0,001Treatment with classical IS1 (8,33%)49 (24,02%)0,303Treatment with cDMARDs1 (8,33%)21 (10,29%)1Treatment with bDMARDs1 (8,33%)8 (3,92%)0,408Treatment with corticosteroids2 (16,66%)38 (18,63%)1Method of administration of CYC Intravenous7 (58,33%)78 (38,24%)1 Oral0 (0%)6 (2,94%)1 Both0 (0%)2 (0,98%)1Total administered dose of CYC (grams)7,28 (±2,36)6,59 (±3,68)0,626Regarding the multivariate analysis, the variables that demonstrated a statistically significant association with the appearance of cancer were age at the time of the study (OR 1.18 [1.02-1.36], p 0.024) and personal history of neoplasia (OR 7.86 [1.30-47.47], p 0.010).ConclusionThe incidence of cancer in patients with autoimmune diseases treated with CYC is not higher with respect to patients with similar diseases treated with other IS. The increased incidence of cancer is associated with the personal history of cancer and older age. Studies with a larger sample size and prospective studies are necessary to verify these results and determine more clearly the associated risk factors.References[1]Dan, D., et al. (2015). Cyclophosphamide: As bad as its reputation?: Long-term single centre experience of cyclophosphamide side effects in the treatment of systemic autoimmune diseases. Swiss Medical Weekly, 144.[2]Baltus, J. A. M., et al. (1983). The occurrence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide: a controlled retrospective follow-up. In Annals of the Rheumatic Diseases (Vol. 42).[3]Kermani, T. A., et al. (2011). Malignancy Risk in Vasculitis. In Therapeutic Advances in Musculoskeletal Disease (Vol. 3, Issue 1, pp. 55–63).Disclosure of InterestsÁfrica Andreu-Suárez: None declared, Marta Serrano Warleta: None declared, Carlos De la Puente Bujidos Speakers bureau: Nordic, Janssen, Boehringer Ingelheim, Pfizer, Consultant of: Gebro, Nordic, Janssen, Boehringer Ingelheim
Subject
General Biochemistry, Genetics and Molecular Biology,Immunology,Immunology and Allergy,Rheumatology