SAFETY AND EFFICACY OF SPLIT-DOSE THIOPURINE VS LOW-DOSE THIOPURINE-ALLOPURINOL CO-THERAPY IN PAEDIATRIC INFLAMMATORY BOWEL DISEASE.

BACKGROUND: Split-dose thiopurine and allopurinol-thiopurine co-therapy strategies have been suggested as rescue therapeutic options for children with inflammatory bowel disease (IBD) and impaired thiopurine metabolism. We compared efficacy and safety of these regimens in patients who previously failed conventional thiopurine treatment.

METHODS: Children with IBD treated with split-dose thiopurine or low-dose thiopurine-allopurinol co-therapy were retrospectively identified. Medical records were reviewed for demographics, treatment regimen, reason for thiopurine failure, side effects and discontinuation of treatment. Laboratory findings were evaluated at different time points.

RESULTS: Following prior therapeutic failure, 42 patients were on split-dose regimen (Group A), 20 patients on thiopurine-allopurinol co-therapy (Group B). Twelve patients crossed from group A to group B due to treatment failure, 1 patient was lost at follow-up, 1 patient discontinued the treatment. The final co-therapy group includes 29 children (Group C), whilst split-dose group (Group D) 31 children.Intention-to-treat analysis showed significant differences between split-dose regimen and thiopurine-allopurinol co-therapy for 6-TGN/6-MeMP ratio (p<0.001), 6-TGN (p<0.05) and 6-MeMP (p<0.001) at 1-3 months. As per protocol analysis, there was a significant difference between group C and group D at 6 months for 6-MeMP (p<0.05) and 6-TGN/6-MeMP ratio (p<0.05), and at 12 months for 6-MeMP (p<0.05) and 6-TGN/6-MeMP ratio (p<0.001). Side effects were more frequent in allopurinol-thiopurine co-therapy (p<0.05).

CONCLUSION: In children with IBD and impaired thiopurine metabolism, split-dose thiopurine and low-dose thiopurine-allopurinol co-therapy are both effective therapeutic strategies. The latter shows higher efficacy but higher side effects rate, suggesting the use of split-dose regimen as first line approach.