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|Title:||Azathioprine dose escalation in inflammatory bowel disease|
|Citation:||Alimentary Pharmacology & Therapeutics, 2004; 20(1):65-71|
|Publisher:||Blackwell Publishing Ltd|
|C.K. Rayner, A.L. Hart, C.M.M. Hayward, A.V. Emmanuel & M.A. Kamm|
|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.|
|Keywords:||Humans; Colitis, Ulcerative; Crohn Disease; Azathioprine; Immunosuppressive Agents; Treatment Outcome; Retrospective Studies; Drug Evaluation; Dose-Response Relationship, Drug; Adult; Middle Aged; Female; Male|
|Description:||The definitive version is available at www.blackwell-synergy.com|
|Appears in Collections:||Medicine publications|
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