Background: The use of 6-Thioguanine nucleotide (6-TGN) levels as a method of adjusting Thiopurine dosing, thus optimizing therapeutic effects, have dramatically improved the safety of their use in Paediatric Inflammatory Bowel Disease (pIBD). The study aim was to evaluate the therapeutic outcomes of pIBD patients treated with either Thiopurine dose splitting (Group 1) or Allopurinol and Thiopurine Co-Therapy (Group 2) (Thiopurine dose reduced to 25% of 2mg/kg, Allopurinol 50mg <30kg weight, 100mg >30kg) for either abnormal level outside the therapeutic range of 235 to 450 pmol/8×10E8 RBC and/or abnormal 6-TGN/MeMP ratios (>11). Both are effective treatment options and although data is available in adult IBD on either regimen, there is paucity of data in pIBD patients.
Methods: 136 patients (male n=81, age range 4 years 10 months–16 years 8 months, median 13 years) on Thiopurines with recorded metabolites were retrospectively identified over a 26 month period from a database.
101 (74%) of patients had levels within the therapeutic range with normal ratios. The two regimens above were implemented on those with abnormal result, n=35 (26%).
Results: In Group 1, n=22 patients were identified; the pre-intervention 6-TGN levels had a median of 199, range 75–521; post-intervention 245, range 123–577. The pre-intervention ratio had a median of 14.5, range 2–32; post-intervention 5, range 0–18. 18 patients had a ratio of >11, in n=17 (77%) the ratio median drop was 11, range 4–31, the biggest drops were with pre-intervention ratios of >18, with 19/22 (86%) patients returning to ratios <11. The pre-intervention MeMP levels had a median of 3179, range 219–5902, post intervention 1496, range 143–3805.
In Group 2, n=13 patients were identified; the pre-intervention 6-TGN levels had a median of 186, range 75–387; post-intervention 309, range 156–578. The pre-intervention ratio had a median of 15, range 8–34; post-intervention 1, range 0–6; 12/13 (92%) patients had a ratio of >11, in those the ratio median drop was 14, range 6–34 with 11/12 having median ratio of 1, range 0–2; The pre-intervention MeMP levels had a median of 2539, range 648–6333, post intervention 246, range 116–2306. There was a statistically significant difference regarding 6-TGN levels in the slit dose versus Co-therapy (0.04) and in the drop in ratio (0.013) favoring the Co-therapy treatment. There was no statistically significant difference in the MeMP levels (0.073)
Conclusions: Although both groups lowered the abnormal levels/ratios, Co-therapy was superior to split dose in our patient cohort. Low-dose Thiopurines and Allopurinol co-therapy is a safe and effective treatment option in pIBD, however needs close monitoring to avoid myelotoxicity. Larger patient numbers are needed to confirm our data.