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P438. Intolerance to IBD treatment in over 1,800 patients in the Oxford IBD Cohort

A. Kent, H. Gray-Stephens, A.-M. Castaneanu, J. Brooks, P. Siddhanathi, S. Travis, H. Uhlig, S. Keshav, Oxford University Hospitals Trust, Translational Gastroenterology Unit, Oxford, United Kingdom

Background

Managing inflammatory bowel disease (IBD) typically requires long-term medication, including combination therapy. Side effects are widely recognised, however the rate is usually evaluated only for individual drugs.

Methods

Retrospective data from 1889 patients consented to the Oxford IBD cohort study (REC 09/H1204/30) was used to evaluate intolerance. Entries in the Oxford IBD research database were confirmed by review of the medical record.

Results

52% patients were female and 50% had Crohn's Disease (CD). 353 (19%) of all patients reported 538 intolerances, with CD accounting for 61%. 88 (5%) reported intolerance to 2 drugs, 28 (2%) to 3 drugs and 11 (1%) to 4 drugs.

Immunomodulator drugs (IMDs): 61% of intolerances were to thiopurines. 255 (42%) of patients treated with azathioprine (AZA) were intolerant & 120 of these were switched to 6-mercaptopurine (6-MP). Of these, 62 (52%) were intolerant of 6-MP. Specific conditions requiring AZA/6-MP withdrawal included leucopenia (56, 10%), deranged liver chemistry (36, 6%), pancreatitis (19, 3%) and single cases of nodular regenerative hyperplasia & haemophagocytic syndrome secondary to EBV. 22% of patients treated with methotrexate (MTX) were intolerant and intolerance increased if there had been previous intolerance to AZA (32%) or 6-MP (42%).

Anti-TNF therapy (ATT): 15% of 433 patients treated with ATT reported intolerance, 18% to infliximab (IFX) and 9% to adalimumab (ADA). In patients with a preceding intolerance to AZA, 24/96 (25%) were intolerant to IFX and 7/53 (13%) were intolerant to ADA. 68% of intolerance were in women. 23 patients treated with ADA had previously reacted to IFX & 3 patients on IFX had reacted to ADA. 118 patients had been treated sequentially with IFX and ADA, and only 7 were intolerant to both. Specific intolerances that required therapy withdrawal included hypersensitivity (28 cases), and single reports of peripheral neuropathy, pneumonitis and dilated cardiomyopathy with IFX, and transient weakness, tuberculosis, psoriaform rash, peripheral neuropathy and angioedema with ADA.

Other medications: Prednisolone & 5-aminosalicylates (5-ASA) had less reported intolerance. They included 4 cases of psychosis on corticosteroids and single cases of acute liver failure and neuropathy with 5-ASA. This probably reflects recording bias towards substantive events on common therapy.

Conclusion

Intolerance to IBD therapy is common, but rarely life-threatening. Half of patients intolerant of AZA were intolerant of 6-MP, and a third intolerant of MTX. Any intolerance of an IMD was associated with a 20% risk of intolerance to ATT. Reported intolerance was less frequent with ADA than IFX, and prior intolerance to IMDs was not associated with increased risk of intolerance to ADA.