Awareness of adverse effects of Azathioprine in patients with Inflammatory Bowel Disease – more to be done?

Editor,

Azathioprine is an important immunomodulator in inflammatory bowel disease (IBD), particularly in the maintenance of remission. Although well tolerated by many patients, there are significant adverse effects, including nausea, leucopenia, pancreatitis, and risk of lymphoma, which require patient education. British Society of Gastroenterology (BSG) guidelines state patients should be offered advisory material on their medications.¹

This study assessed the proportion of IBD patients who received information regarding azathioprine, and their understanding of adverse effects. Patients, who were currently (or recently) taking azathioprine and attending the Gastroenterology Outpatient Department at St. Vincent's University Hospital in Dublin, from June 2010 to May 2011 were invited to complete a short 10-question survey. A 10-question anonymous survey was designed to gather information regarding patients' understanding of azathioprine and its adverse effects (Fig 1). Apart from demographic information patients were asked about duration of treatment with azathioprine, type of information received, current dosage and compliance, understanding of side-effects, frequency of blood tests, adverse effects experienced and their management.

Fig 1.

Azathioprine Questionnaire

RESULTS

96 completed questionnaires (52% male, 48% female) were analysed. Fifty-nine (61%) patients had Crohn's disease, 33 (34%) ulcerative colitis, and 4 had indeterminate colitis. Sixty-two (65%) received information about azathioprine from their physician (23% written, 37% verbal, 39% both written and verbal). 83 of 96 (93%) patients remembered to take their medication daily. 61 (71%) were aware that low WBC counts were a side effect of azathioprine. Eighty-nine (93%) of patients had blood monitoring performed, but the frequency varied widely, from monthly (21; 24%) to less than once every 12 months. Awareness of other side effects was lower - skin rash (38%), pancreatitis (30%), lymphoma (36%). Thirty-eight (40%) patients were unwell while taking azathioprine: of these, 13 (34%) experienced a flu-like illness and 14 (37%) had a sore throat. When unwell, 51% visited their GP, only one third had blood tests, and 20% temporarily stopped azathioprine.

DISCUSSION

BSG guidelines suggest full blood picture (FBP) initially every 2-4 weeks for two months and then bimonthly.¹ Our study showed 24% of patients had their FBP checked monthly, but almost 20% had their FBP checked less than six monthly.

The 2009 Cochrane Review indicated that 28% of 621 patients taking azathioprine experienced side effects.² Severe leucopenia develops in 3% of patients.³ Only one third of our respondents recalled the minor side effects such as rash. However, 71% knew about the risk of a low white cell count. Just over one third of patients (36%) knew about the risk of lymphoma.

While 65% of our patients recalled receiving information about azathioprine, however, as only 14% of verbal medical information is remembered, it is imperative that patients receive additional forms of information - combining verbal and written is ideal.^{4, 5}

In this era of electronic communication the use of devices, such as smart phones, may be relevant in these young patients. ‘Apps’ could provide reminders for the patient and their doctor to have two monthly white cell counts checked – as has been used in HIV patients.