P331 Allopurinol and azathioprine co-therapy or thioguanine dose splitting: shifting the shunters in the mercaptopurine pathway in a paediatric inflammatory bowel disease population—a single-centre experience
S. Chadokufa*1, A. Lozinsky Rolnik2, S. Sider1, N. Acton3, B. Huggett3, N. Shah4, F. Kiparissi1
1Great Ormond Street Hospital, Gastro, London, United Kingdom, 2Great Ormond Street Hospital, Gastro, LONDON, United Kingdom, 3Great Ormond Street, London, United Kingdom, 4Great Ormond Street, Gastro, London, United Kingdom
The use of 6-Thioguanine nucleotide (6-TGN) levels as a method to adjust thiopurine doses thus optimising therapeutic response whilst minimising toxicity has dramatically improved patient’s safety for drug-related side effects; however, they do still occur when patients shunt towards the MeMP pathway. Split-dose thioguanine or allopurinol and low-dose thiopurine co-therapy are effective treatment options. Although data are available from adult inflammatory bowel disease (IBD) patients, there is paucity of data in pIBD. Split-dose regimens and co-therapy were introduced in our unit 1 year ago.
Aim: to evaluate the safety and therapeutic outcome of pIBD patients treated with either split-dose azathioprine or azathioprine and allopurinol co-therapy for raised 6TGN levels (> 450 units) and raised MeMP/6TGN ratios (> 11).
In the split-dose group, 21 patients were identified: male n = 12, median age 11 years, with age range 4–15 years; 10 patients were excluded for insufficient follow-up (< 6 weeks). For the 11 remaining patients, the median length of regime was 7 months (range 2–13 months): 8 had Crohn’s disease, 1 ulcerative colitis, and 2 IBDU. Although in 9 (64%), patient TGN/MeMp ratios normalised to < 11, in 10 (84%) patients, the therapeutic 6-TGN levels where not reached, and, moreover, they actually decreased. Only 1 patient responded to the split-dose regimen with normal 6-TGN levels plus normal ratio. In the co-therapy group, 16 patients were identified: male n = 9, median age 10 years, and age range 4–17, 5 were excluded because of insufficient follow-up and or switched to different therapy. The median length of co-therapy was 6 months (range 3–13 months). Out of the remaining 11 patients, 8 had Crohn’s disease; 1 ulcerative colitis; and 2 IBDU. In addition, 9 (85%) of pre-co-therapy 6-TGN levels were sub-therapeutic. Following co-therapy, 6 of these 9 (66%) moved into the therapeutic 6-TGN range, with normalisation in 90% of previously raised ratios.
Co-therapy treatment was superior to split-dose regimens in our patient cohort.
Co-therapy treatment was superior to split-dose regimens in our patient cohort, demonstrating that low-dose azathioprine and allopurinol co-therapy is a safe and effective treatment option in pIBD. This should encourage trialling co-therapy before considering switching to other medication.