Toxicidade da azatioprina no tratamento da doença de Crohn: frequência, abordagem e evolução

Abstract

Crohn’s disease (CD) is an inflammatory bowel disease whose etiology is unknown and that has its incidence increasing significantly during the last decades. Polymorphous clinical manifestations and a doubtful evolution, sometimes fatal, are the more striking features of its natural history. Until nowadays, there is no curative therapy for CD. Azathioprine (AZA) is one of the most efficient and employed drugs in CD patients,especially those who became dependent or non-responders to corticosteroid treatment. However, AZA is a drug which has a potential toxicity and to try to reduce its side effects it is necessary to know its action mechanism as well the list of potential adverse reactions and how to manage them. Aims: To evaluate the incidence, approach and course of AZA side effects in the treatment of CD patients. Methods and Material: From January 2002 to December 2006 106 CD patients were followed prospectively (45 men and 61 women, with a mean age of 36,3 years – range 12-68) in the outpatient Service of Inflammatory Bowel Disease of Universitary Hospital of Federal University of Juiz de Fora, Brazil, and being treated with AZA. Socio-demographic, clinical features of CD patients, AZA doses and time of using, and concomitant other drugs used were registered. All patients were submitted to laboratorial routine for toxicity monitoring during the treatment. Thus, red and white blood cell count and measurement of aminotransferases and amilase levels were analysed at the study beginning; subsequent monitoring included red and white blood cell count at every two weeks for the first two months and lately every four to eight weeks. Aminotransferases levels were determinated every three months. Moreover, all the patients were instructed to search for medical assistance in case of any sign of infections as well as sore throat. Leucopoenia was defined as white blood cells count below 4.000/mm³, and severe as lower 2.000/mm³; trombocytopenia when platelets count were under 130.000/mm³. AZA was stopped or doses reduced when fever, adverse reactions or toxicity AZA-related and associated diseases occurred. In order to comparison, subgroups of patients were studied separately, those with and without AZA-toxicity. Results: 56 (52,7%) patients presented at least one side effect needing transient dose reduction; 18 (17%) had to interrupt definitively the AZA ministration, most of them in consequence of hypersensitivity reactions. Slight nausea and vomits occurred in 29 (27,4%); black race and those with co morbidities have had much more gastrointestinal intolerance than white and those without any other associated disease (p=0,04). Leucopoenia was the most frequent adverse reaction, observed in 36 (34%) and the time of AZA using was higher in patients with leucopoenia than in those nonleucopoenics (p=0,001). However, the mean dose of AZA was lower in patients with leucopoenia than in those non-leucopoenics (p=0,005). No one serious infection, malignant tumors or death occurred during AZA treatment. Conclusions: The AZA use showed to be a reasonable safe drug in CD treatment since that a clinical and laboratorial serious control is performed during all the time of therapy.