Forty percent of patients with inflammatory bowel disease show no response to standard dose azathioprine.
Therefore doctors at St. Mark's Hospital in Middlesex, England, have conducted a study to evaluate the efficacy and safety of increasing this dose, according to a fixed schedule, and guided by clinical response and adverse effects.
To do this, they reviewed the records of all patients with inflammatory bowel disease treated by a single clinician over 6 years.
All patients were unresponsive to at least 3 months treatment with standard dose azathioprine (2 mg/kg/day). In each case the standard dose had subsequently been increased.
A total of 40 patients were evaluated in the study. Twenty-seven were male, 24 were Crohn's sufferers and 16 had ulcerative colitis.
| Increasing dosage to 2.5 mg/kg/day can be beneficial for patients unresponsive to lower doses|
|Alimentary Pharmacology & Therapeutics|
Each patient had either chronic active disease or else recurrent flares despite having received standard dose azathioprine for a median 8 months (range 3 to 114 months).
Dosages were increased from a median 2.02 (1.61 to 3.19) mg/kg/day to 2.72 (2.37 to 3.99) mg/kg/day in one to four increments of 0.5mg/kg/day, with all patients being followed up for a median 6 (0.5 to 54) months.
Of the 40 patients, a total of 11, comprising 7 Crohn's and 4 ulcerative colitis cases, responded positively, or had reduced frequency of flare-ups at the end of follow-up.
In the case of 17 patients, there was no apparent benefit at all to increased dose of azathioprine.
The research group found responses were more likely for maximum doses of 2.5 mg/kg/day (6 of 11 patients) than for doses greater than this (5 of 29 patients).
Treatment had to be discontinued at increased dosage in 12 patients, due to adverse side effects. These included leukopenia (8 patients), nausea (3 patients), and raised liver enzymes (1 patient). In each instance, these side effects were transient and reversible.
The scientists conclude, "Increasing the azathioprine dose up to 2.5 mg/kg/day appears beneficial in patients who have not responded to 2 mg/kg/day."
However, they warn that, "Further increase above 2.5 mg/kg/day is less likely to be efficacious, and is associated with a substantial risk of adverse reactions."