P565. Clinically significant safety issues during long-term azathioprine use in patients with ulcerative colitis
K. Katsanos1, V. Tsianos1, S. Zachariadou1, I. Vagias1, S. Liamas1, A. Tatsioni2, D. Sigounas1, I. Mitselos1, D. Christodoulou1, E. Tsianos1, for the NW Greece IBD Study Group, 1University of Ioannina, Ioannina, Greece, 2Department of Family Medicine University of Ioanninaand Tufts-New England Medical Center Evidence-Based Practice Center, Institute for Clinical Research and Health Policy Studies, Boston, USA
The aim of the study was to investigate the long-term safety of azathioprine (AZA) in patients with ulcerative colitis (UC).
Tertiary referral center retrospective IBD chart study. In total 443 UC patient files were retrieved for any AZA use during a 30-year period 1981–2010. Patient data included demographics, clinical information on diagnosis and therapy and routine laboratory tests. Diagnosis of UC was based on clinical, endoscopic and histologic criteria. All UC patients who were currently on AZA or who had received AZA in the past were included in statistical analysis.
In total 72 UC patients (46 males) aged 47.3 years (range 16–80) were analyzed. Disease location was proctitis in 11 (15.3%), left-sided colitis in 35 (48.6%) and pancolitis in 26 (36.1%). The median follow up time was 7.3 years (range 0.5 to 16 years) and the median dose of AZA was 100 mg/day (range 50–200 mg). Six patients (8.3%) underwent bowel surgery while on AZA. Permanent discontinuation of AZA was decided in 7/72 (9.7%) patients due to bone marrow toxicity (leucopenia or/and anemia) while in 6 (8.3%) patients AZA dose was decreased due to hepatotoxicity. Transient aphthous stomatitis was observed in 2 patients and 1 patient experienced significant but reversible hair fall. Infections were recorded in 17 (23.6%) patients (11/17 microbial) of whom 4 needed hospitalization. No case of allergic pancreatitis was recorded. Two patients (2.8%) were diagnosed with basal cell skin cancers and were treated with local surgery. During follow up 4 deaths (5.6%) unrelated to the use of AZA were recorded.
According to this thirty-year observational study on AZA use in UC in total 19/72 (26.3%) patients presented with clinically significant safety issues the most frequent being bone marrow toxicity. Azathioprine permanent discontinuation or dose decrease was needed in 13/72 (18%) of patients and 2 skin cancers (2.8%) were recorded. Hospitalization for infection was needed in 4 (5.5%) patients.