Rayner, C.Hart, A.Hayward, C.Emmanuel, A.Kamm, M.2006-06-262006-06-262004Alimentary Pharmacology and Therapeutics, 2004; 20(1):65-710269-28131365-2036http://hdl.handle.net/2440/9182The definitive version is available at www.blackwell-synergy.comBackground: 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.enHumansColitis, UlcerativeCrohn DiseaseAzathioprineImmunosuppressive AgentsTreatment OutcomeRetrospective StudiesDrug EvaluationDose-Response Relationship, DrugAdultMiddle AgedFemaleMaleJournal article002004191210.1111/j.1365-2036.2004.02009.x0002222868000082-s2.0-314274814255949Rayner, C. [0000-0002-5527-256X]