Effect of Azathioprine Intolerance on Outcomes of IBD
Two hundred and thirty-nine patients met the inclusion criteria for this study and consisted of 141 patients with CD and 98 patients with UC. The median age of this cohort was 38 years and 32.5% of patients were male. The mean follow-up was 13.5 years.
Overall, 28.0% of patients were intolerant of azathioprine (n=67). The median age of patients was 47 years and 26.9% of patients were male. The most common reason for intolerance was nausea and vomiting (34.3%), deranged liver function tests (LFTs, 28.4%) and headaches (11.9%) ( Table 1 ). After the unsuccessful introduction of azathioprine, this cohort of patients was subsequently treated with infliximab (20.9%), mercaptopurine (10.4%), methotrexate (6.0%) and adalimumab (4.5%) ( Table 2 ).
Of the 141 patients with CD, 35 (24.8%) were intolerant to azathioprine. Azathioprine was not tolerated owing to gastrointestinal side effects in 53.6% (nausea/vomiting), headaches in 17.9%, deranged LFTs in 17.9%
Within the CD cohort, 68 (48.2%) patients required surgery during the follow-up period. Rates of surgery did not differ between patients who were azathioprine intolerant or tolerant. The median time from diagnosis to time of surgery was 3.9 years in those who were azathioprine tolerant and 7.4 years in those who were azathioprine intolerant. There was a significant difference between the azathioprine-intolerant and -tolerant cohorts in the number who were steroid dependent (p<0.001). The Harvey Bradshaw Index was statistically different between the cohorts; nearly 25% fewer patients were in clinical remission and 20% more had moderate/severe disease in the azathioprine-intolerant cohort (p<0.001) ( Table 3 ).
Of the 98 patients with UC, 32 (32.7%) were intolerant to azathioprine. Azathioprine was not tolerated owing to deranged LFTs in 43.3%, gastrointestinal symptoms of nausea/vomiting in 23.3%, cutaneous side effects in 10.0%, migraines in 6.7% and infections in 3.3%.
In the UC cohort, 17 (17.3%) patients required surgery during the follow-up period. Rates of surgery were not different between patients who were azathioprine intolerant or tolerant. The median time from diagnosis to time of surgery was 4.4 years in those who were azathioprine tolerant and 2.4 years in those who were azathioprine intolerant. These differences were not statistically significant. More patients in the azathioprine-intolerant cohort were steroid dependent (p<0.001). However, azathioprine intolerance did not have a statistically significant effect on disease activity ( Table 4 ).
An analysis of the baseline demographics of azathioprine-intolerant patients was performed. Patients intolerant to azathioprine were significantly more likely to be female (relative risk (RR)=1.56, p=0.038) and aged 50–70 years (RR=1.61, p=0.010).
Results
Two hundred and thirty-nine patients met the inclusion criteria for this study and consisted of 141 patients with CD and 98 patients with UC. The median age of this cohort was 38 years and 32.5% of patients were male. The mean follow-up was 13.5 years.
Azathioprine-intolerant Cohort
Overall, 28.0% of patients were intolerant of azathioprine (n=67). The median age of patients was 47 years and 26.9% of patients were male. The most common reason for intolerance was nausea and vomiting (34.3%), deranged liver function tests (LFTs, 28.4%) and headaches (11.9%) ( Table 1 ). After the unsuccessful introduction of azathioprine, this cohort of patients was subsequently treated with infliximab (20.9%), mercaptopurine (10.4%), methotrexate (6.0%) and adalimumab (4.5%) ( Table 2 ).
Crohn's Disease Cohort
Of the 141 patients with CD, 35 (24.8%) were intolerant to azathioprine. Azathioprine was not tolerated owing to gastrointestinal side effects in 53.6% (nausea/vomiting), headaches in 17.9%, deranged LFTs in 17.9%
Within the CD cohort, 68 (48.2%) patients required surgery during the follow-up period. Rates of surgery did not differ between patients who were azathioprine intolerant or tolerant. The median time from diagnosis to time of surgery was 3.9 years in those who were azathioprine tolerant and 7.4 years in those who were azathioprine intolerant. There was a significant difference between the azathioprine-intolerant and -tolerant cohorts in the number who were steroid dependent (p<0.001). The Harvey Bradshaw Index was statistically different between the cohorts; nearly 25% fewer patients were in clinical remission and 20% more had moderate/severe disease in the azathioprine-intolerant cohort (p<0.001) ( Table 3 ).
Ulcerative Colitis Cohort
Of the 98 patients with UC, 32 (32.7%) were intolerant to azathioprine. Azathioprine was not tolerated owing to deranged LFTs in 43.3%, gastrointestinal symptoms of nausea/vomiting in 23.3%, cutaneous side effects in 10.0%, migraines in 6.7% and infections in 3.3%.
In the UC cohort, 17 (17.3%) patients required surgery during the follow-up period. Rates of surgery were not different between patients who were azathioprine intolerant or tolerant. The median time from diagnosis to time of surgery was 4.4 years in those who were azathioprine tolerant and 2.4 years in those who were azathioprine intolerant. These differences were not statistically significant. More patients in the azathioprine-intolerant cohort were steroid dependent (p<0.001). However, azathioprine intolerance did not have a statistically significant effect on disease activity ( Table 4 ).
Predictors of Azathioprine Intolerance
An analysis of the baseline demographics of azathioprine-intolerant patients was performed. Patients intolerant to azathioprine were significantly more likely to be female (relative risk (RR)=1.56, p=0.038) and aged 50–70 years (RR=1.61, p=0.010).
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