Original Article
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World J Gastroenterol. Aug 14, 2013; 19(30): 4877-4886
Published online Aug 14, 2013. doi: 10.3748/wjg.v19.i30.4877
Thiopurines related malignancies in inflammatory bowel disease: Local experience in Granada, Spain
María Gómez-García, Maria José Cabello-Tapia, Antonio Damián Sánchez-Capilla, Javier De Teresa-Galván, Eduardo Redondo-Cerezo
María Gómez-García, Maria José Cabello-Tapia, Inflammatory Bowel Disease Unit, Department of Gastroenterology, University Hospital Virgen de Las Nieves, 18014 Granada, Spain
Antonio Damián Sánchez-Capilla, Javier De Teresa-Galván, Department of Gastroenterology, University Hospital Virgen de Las Nieves, 18014 Granada, Spain
Eduardo Redondo-Cerezo, Endoscopy Unit, Department of Gastroenterology, University Hospital Virgen de Las Nieves, 18014 Granada, Spain
Author contributions: Gómez-García M designed the study, gathered the data; Gómez-García M, Redondo-Cerezo E and De Teresa-Galván J reviewed the article; Cabello-Tapia MJ and Sánchez-Capilla AD reviewed theliterature; Sánchez-Capilla AD analysed the data and written the article; Redondo-Cerezo E translated the article.
Correspondence to: María Gómez-García, MD, PhD, Inflammatory Bowel Disease Unit, Department of Gastroenterology, University Hospital Virgen de Las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain. mmrosarioes@yahoo.es
Telephone: +34-958-020363 Fax: +34-958-120169
Received: June 5, 2012
Revised: August 25, 2012
Accepted: September 12, 2012
Published online: August 14, 2013
Abstract

AIM: To investigate the incidence of neoplasms in inflammatory bowel disease (IBD) patients and the potential causative role of thiopurines.

METHODS: We performed an observational descriptive study comparing the incidence of malignancies in IBD patients treated with thiopurines and patients not treated with these drugs. We included 812 patients which were divided in two groups depending on whether they have received thiopurines or not. We have studied basal characteristics of both groups (age when the disease was diagnosed, sex, type of IBD, etc.) and treatments received (Azathioprine, mercaptopurine, infliximab, adalimumab or other immunomodulators), as well as neoplasms incidence. Univariate analysis was performed with the student t test, χ2 test or Wilcoxon exact test as appropriate. A logistic regression analysis was performed as multivariate analysis. Statistical significance was establish at P values of less than 0.05, and 95%CI were used for the odds ratios.

RESULTS: Among 812 patients included, 429 (52.83%) have received thiopurines: 79.5% azathioprine, 14% mercaptopurine and 6.5% both drugs. 44.76% of patients treated with thiopurines and 46, 48% of patients who did not receive this treatment were women (P > 0.05). The proportion of ulcerative colitis patients treated with thiopurines was 30.3% compare to 66. 67% of patients not treated (P < 0.001). Mean azathioprine dose was 123.79 ± 36.5 mg/d (range: 50-250 mg/d), mean usage time was 72.16 ± 55.7 mo (range: 1-300 mo) and the accumulated dose along this time was 274.32 ± 233.5 g (1.5-1350 g). With respect to mercaptopurine, mean dose was 74.7 ± 23.9 mg/d (range: 25-150 mg/d), mean usage time of 23.37 ± 27.6 mo (range: 1-118 mo), and the accumulated dose along this time was 52.2 ± 63.5 g (range: 1.5-243 g). Thiopurine S-methyltransferase activity was tested in 66% of patients treated with thiopurines, among which 98.2% had an intermediate or high activity. Among the patients treated with thiopurines, 27.27% (112 patients) and 11.66% (50 patients) received treatment with Infliximab and Adalimumab respectively, but only 1.83% (7 patients) and 0.78% (3 patients) received these drugs in the group of patients who did not received thiopurines (P < 0.001 and P < 0.001 respectively). Finally, 6.8% (29 patients) among those treated with thiopurines have received other immunesupresants (Methotrexate, Tacrolimus, Cyclosporin), compare to 1% (4 patients) of patients not treated with thiopurines (P < 0.001). Among patients treated with thiopurines, 3.97% developed a malignancy, and among those not treated neoplasms presented in 8.1% (P = 0.013). The most frequent neoplasms were colorectal ones (12 cases in patients not treated with thiopurines but none in treated, P < 0.001) followed by non-melanoma skin cancer (8 patients in treated with thiopurines and 6 in not treated, P > 0.05).

CONCLUSION: In our experience, thiopurine therapy did not increase malignancies development in IBD patients, and was an efective and safe treatment for these diseases.

Keywords: Malignancy; Neoplasm; Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Thiopurines; Azathioprine; Mercaptopurine