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PTU-075 Long Term outcome of Azathioprine Therapy in 353 Consecutive IBD Patients

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Introduction Thiopurines are the mainstay of therapy in Inflammatory Bowel Disease (IBD). Azathioprine (AZA) and Mercaptopurine are very effective at maintaining remission but have a wide range of side effects which can limit their use as long term maintenance therapy. To assess how effective AZA was in IBD, and what its limitations were, the outcome of 353 consecutive IBD patients started on AZA with at least onw year follow up was assessed. Methods Since 2005 all patients started on AZA for IBD have been recorded and monitored. These data were then used to assess the outcomes of patients where there had been at least one year of follow up. Outcomes recorded were whether AZA was still being taken or not. If still being taken information about the disease activity was recorded. If AZA therapy had been discontinued then the reason for this was recorded and subsequent therapeutic interventions noted. Results 353 patients had started AZA and had at least one year of follow up. TPMT status was checked in all patients. Dosing was as follows: low TPMT; 50mg and increased as tolerated. Normal TPMT; 2–2.5mg/kg. Of the 353 patients, 204 had Crohn’s disease (CD), 141 had Ulcerative Colitis and 8 had IBD-unclassified. The male:female ratio was 184:169 (52.1% male). Age range was 16–86 years (mean; 46). 322/353 (91%) remain under follow up. 127 (36%) of patients stopped taking AZA at one year. After six years 152 (43.1%) remained on AZA, 182 (51.6%) had stopped and in 19 (5%) the outcome was unknown. Nausea and myalgia were the main reasons for stopping AZA. 40(11.3%) patients developed hepatitis (ALT rise > 2xULN), 6 (1.7%) developed myelosuppression and 7 (2%) developed pancreatitis (consistent clinical presentation and raised amylase). Of the 182 patients who stopped AZA, 67 (37.8%) had an escalation of therapy – 20 started methotrexate, 18 started biologics and 29 underwent surgery. Of the 152 who continued AZA, 138 (90.8%) were in a clinical remission based on clinical assessment supported by normal C-reactive protein in 126 (91.3%), Harvey Bradshaw Index in those with CD 55 (40%) patients and endoscopic findings in 22 (15.9%). 112 (73.6%) patients had blood monitoring (FBC and LFTs) at least quarterly and 147 (96.7%) at bi-annually. Conclusion For such an important drug in IBD management a significant number of patients stop AZA due to side effects. This study highlights these so that patients can be accurately informed. It also highlights that AZA when tolerated is a very effective maintenance medication. Published data from our own and other units suggest that low-dose AZA in combination with allopurinol reduces side effects and increases tolerability and may make AZA a more effective longterm maintenance agent. Disclosure of Interest None Declared
Title: PTU-075 Long Term outcome of Azathioprine Therapy in 353 Consecutive IBD Patients
Description:
Introduction Thiopurines are the mainstay of therapy in Inflammatory Bowel Disease (IBD).
Azathioprine (AZA) and Mercaptopurine are very effective at maintaining remission but have a wide range of side effects which can limit their use as long term maintenance therapy.
To assess how effective AZA was in IBD, and what its limitations were, the outcome of 353 consecutive IBD patients started on AZA with at least onw year follow up was assessed.
Methods Since 2005 all patients started on AZA for IBD have been recorded and monitored.
These data were then used to assess the outcomes of patients where there had been at least one year of follow up.
Outcomes recorded were whether AZA was still being taken or not.
If still being taken information about the disease activity was recorded.
If AZA therapy had been discontinued then the reason for this was recorded and subsequent therapeutic interventions noted.
Results 353 patients had started AZA and had at least one year of follow up.
TPMT status was checked in all patients.
Dosing was as follows: low TPMT; 50mg and increased as tolerated.
Normal TPMT; 2–2.
5mg/kg.
Of the 353 patients, 204 had Crohn’s disease (CD), 141 had Ulcerative Colitis and 8 had IBD-unclassified.
The male:female ratio was 184:169 (52.
1% male).
Age range was 16–86 years (mean; 46).
322/353 (91%) remain under follow up.
127 (36%) of patients stopped taking AZA at one year.
After six years 152 (43.
1%) remained on AZA, 182 (51.
6%) had stopped and in 19 (5%) the outcome was unknown.
Nausea and myalgia were the main reasons for stopping AZA.
40(11.
3%) patients developed hepatitis (ALT rise > 2xULN), 6 (1.
7%) developed myelosuppression and 7 (2%) developed pancreatitis (consistent clinical presentation and raised amylase).
Of the 182 patients who stopped AZA, 67 (37.
8%) had an escalation of therapy – 20 started methotrexate, 18 started biologics and 29 underwent surgery.
Of the 152 who continued AZA, 138 (90.
8%) were in a clinical remission based on clinical assessment supported by normal C-reactive protein in 126 (91.
3%), Harvey Bradshaw Index in those with CD 55 (40%) patients and endoscopic findings in 22 (15.
9%).
112 (73.
6%) patients had blood monitoring (FBC and LFTs) at least quarterly and 147 (96.
7%) at bi-annually.
Conclusion For such an important drug in IBD management a significant number of patients stop AZA due to side effects.
This study highlights these so that patients can be accurately informed.
It also highlights that AZA when tolerated is a very effective maintenance medication.
Published data from our own and other units suggest that low-dose AZA in combination with allopurinol reduces side effects and increases tolerability and may make AZA a more effective longterm maintenance agent.
Disclosure of Interest None Declared.

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