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P678 Did toxicity profile of azathioprine changed within the last 10 years: comparative 17 years data from a single tertiary IBD center

Bozcan S., Hatemi I., Yıldırım S., Demir N., Erzin Y., Celik A.F.

Istanbul University Cerrahpasa School of Medicine, Gastroenterology, Istanbul, Turkey

Background

We aimed to evaluate the toxicity profile of the AZA. We obtained the information from our 17 years old IBD registry. We also wished to compare the parameters of these current information with our a decade old previously registered IBD data.

Methods

We reviewed the charts of our IBD outpatient clinic from 1999 to 2016.

Results

2200 patients (pts) were evaluated retrospectively, among them 601 (27%) were treated with AZA (264 F 45% and 321 M 55%) with a mean duration of treatment 41.8±40.7 months (mo) (range: 0.25–244 mo median: 30 mo). Diagnosis was CD in 67%,UC in 29%, ID colitis in 4%. AZA toxicity was observed in 25% and AZA was discontinued in 22%. The causes of drug withdrawal are shown in the table 1. In 65% of the pts who had developed adverse events, the duration of AZA use was less than 12 mo. A total of 65 pts have had leukopenia, in 31 (5%) of these pts AZA dosage was reduced, in 25 pts (4%) therapy could had been continued with dose reduction. In 40 pts AZA therapy was stopped due to leukopenia, 2 pts were hospitalized with febrile neutropenia for both GSF was needed. Five pts had developed drug rash which required drug withdrawal. One of them was diagnosed as AZA related Sweet Syndrome. Two pts have had severe myalgia. There were 5 pts who had malignancy during the follow-up period (vulvar ca, AML, gastric ca, breast ca, renal cell ca). The past AZA toxicity rates of leukopenia, GI intolerance, pancreatitis and hepatotoxicity in 2007 were respectively: 8%,6%,1.3%, 1.9% in 151 pts with a mean duration of AZA use of 23.8 mo. When compared with the past, toxicity rates are similar. AZA toxicity which necessitates drug discontinuation were twice more common in our recent IBD pts than the pts in our historical cohort. As a not fairly well described entity GI intolerance seems to happen just after taking AZA with similar GI symptoms to pancreatitis without any increase in amylase and very quick disappearance of symptoms in case of cession of AZA.

Table 1. The toxicity and withdrawal rates of azathioprine

Side effectsWithdrawal rateAge at the time of toxicityMean time to toxicityConcomitant 5-ASAConcomitant CSConcomitant anti-TNF
N (%)mean ± SD%%%
Leukopenia40/601 (6.8%)47.4±14.212.9±15.1 (1–62) months705025
Pancreatitis26/601 (4.3%)36.3±11.83.8±8.1 months46.234.57.7
Hepatotoxicty17/601 (2.8%)36.5±14.17±6.5 months58.858.829.4
Gastrointestinal intolerance34/601 (5.6%)39±11.51.1±0.4 (0–2) weeks52.935.320.6

Conclusion

As most of the side effects occurred within a year period, and the long term AZA use didn't change the prevalence of the adverse events, AZA use seems to be safer and the toxicity is lower when the use is longer than a year without toxicity. Although the current cohort is bigger and the duration of AZA use is nearly twice longer than the historical cohort the rate of AZA toxicity did not increase by the time. Increase in AZA withdrawal nearly two fold within a decade may need attention but may still have some influence from the biologic era necessities.