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P550. Azathioprine and lymphocyte count in paediatric inflammatory bowel disease

E. Volonaki, V. La Vela, R. Dziubac, F. Kiparissi, N. Shah, K.J. Lindley, M. Elawad, Great Ormond Street Hospital, Paediatric Gastroenterology, London, United Kingdom

Background

Azathioprine (AZA) is well established in the treatment of inflammatory bowel disease (IBD) in children and adults. It inhibits biosynthesis of purine nucleotides, suppressing proliferation and inducing lymphocyte apoptosis. The value of lymphocyte count in monitoring patients on AZA treatment is not well defined. The aim of our study was to determine how AZA treatment affects the lymphocyte count in paediatric patients with IBD during the first 6 months of treatment.

Methods

We conducted a retrospective study on children with IBD who started treatment with AZA between 2009 and 2013. Patients with intermediate or low Thiopurine Methyltransferase (TPMT) activity who would be at increased risk of developing leucopenia and lymphopenia were excluded from the study. Patients on biologicals or other immunosuppressants apart from steroids were also excluded. Lymphocyte and leucocyte counts at baseline, 1 month, 3 months and 6 months on treatment were compared. To establish the effect of AZA dose on lymphocyte count patients were stratified in two groups: lower dose group if they received <1.5 mg/kg of AZA and higher dose group if they received ≥1.5 mg/kg of AZA. Statistical analysis with Wilcoxon matched pairs test was performed.

Results

31 patients (14 females, median age 10.6 years, range 4.2 to 15.6 years) were included. Majority of patients were diagnosed with Crohn's disease (16/31, 51.6%), while 8/31 (25.8%) had IBD-unclassified and 7/31 (22.6%) had ulcerative colitis. Patients received a mean overall AZA dose of 1.8±0.6 mg/kg. Patients on higher AZA dose had significantly lower median lymphocyte counts at 3 months (p = 0.04) and at 6 months of treatment (p = 0.002) compared to baseline. Patients on lower AZA dose also dropped their lymphocyte counts at 6 months (p = 0.04). Regardless of AZA dose used, lymphocyte count was suppressed at 6 months after onset of treatment (p = 0.01). Total white cell count was decreased and remained significantly lower from the first month of treatment compared to baseline. No patient developed leukopenia or lymphopenia. 28/31 (90.3%) patients were in remission off steroids at the end of 6 months. Of the remaining three patients (3/31, 9.7%), only one failed to suppress his lymphocyte count despite being on high AZA dose.

Conclusion

Children with IBD suppressed their lymphocyte counts in the first six months of AZA treatment. 90.3% of patients remained in remission off steroids at six months. We propose that lymphocyte suppression is a good and simple marker of response to AZA treatment. Larger studies on predicting response to AZA according to dosing and lymphocyte count are required.