Azathioprine dose escalation in inflammatory bowel disease
Date
2004
Authors
Rayner, C.
Hart, A.
Hayward, C.
Emmanuel, A.
Kamm, M.
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Advisors
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Journal article
Citation
Alimentary Pharmacology and Therapeutics, 2004; 20(1):65-71
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C.K. Rayner, A.L. Hart, C.M.M. Hayward, A.V. Emmanuel & M.A. Kamm
Conference Name
Abstract
Background: Forty per cent of patients with inflammatory bowel disease fail to respond to standard dose azathioprine (2 mg/kg/day). Aims: To evaluate the efficacy and safety of increasing the azathioprine dose according to a fixed schedule and guided by clinical response and adverse effects.Methods: We reviewed the records of all patients with inflammatory bowel disease treated by a single clinician over 6 years, unresponsive to at least 3 months treatment with standard dose azathioprine, and whose dose was subsequently increased. Results: Forty patients (27 male; 24 Crohn's, 16 ulcerative colitis) with chronic active disease or recurrent flares despite standard dose azathioprine for a median 8 months (range 3–114) increased their dose from a median 2.02 (1.61–3.19) mg/kg/day to 2.72 (2.37–3.99) mg/kg/day in one to four increments of 0.5 mg/kg/day, and were followed over a median6 (0.5–54) months. Eleven of the 40 patients (seven Crohn's, four ulcerative colitis) responded or had reduced frequency of flare-ups at the end of follow-up, while 17 of the 40 patients had no benefit. Response was more likely for maximum doses ≤2.5 mg/kg/day (six of 11 patients) than for doses >2.5 mg/kg/day (five of 29 patients) (P = 0.042). Twelve patients (11 of whom received maximum doses >2.5 mg/kg/day) were unable to maintain an increased azathioprine dose because of leukopenia in eight, nausea in three, and raised liver enzymes in one (all transient and reversible). Conclusions: Increasing the azathioprine dose up to 2.5 mg/kg/day appears beneficial in patients who have not responded to 2 mg/kg/day. Further increase above 2.5 mg/kg/day is less likely to be efficacious, and is associated with a substantial risk of adverse reactions.
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