Safety and Efficacy of Split-Dose Thiopurine vs Low-Dose Thiopurine-Allopurinol Cotherapy in Pediatric Inflammatory Bowel Disease

Clinical and Translational Gastroenterology · 10 authors, 3 centres

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TL;DR

This retrospective cohort study compared split-dose thiopurine and low-dose thiopurine-allopurinol cotherapy in children with IBD who failed conventional thiopurines, finding both are effective, but cotherapy had higher metabolite normalization rates and a higher side effect rate.

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The final analysis included 31 patients on SDT and 29 on LDTA. Intention-to-treat analysis showed LDTA was significantly more effective at normalizing thiopurine metabolite levels within 1-3 months. Side effects were significantly more frequent with LDTA (20% vs 3%). The study concludes both strategies are effective, but the higher side effect rate with LDTA suggests SDT may be preferable as a first-line approach. Limitations include the retrospective design and lack of objective clinical remission measures.

STUDY TYPE

cohort

SPECIALTY

pediatrics

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ORIGINAL PAPER

PMC10043576

Safety and Efficacy of Split-Dose Thiopurine vs Low-Dose Thiopurine-Allopurinol Cotherapy in Pediatric Inflammatory Bowel Disease

Clinical and Translational Gastroenterology

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ABSTRACT

INTRODUCTION: Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been suggested as rescue therapeutic options for children with inflammatory bowel disease (IBD) and impaired thiopurine metabolism. We compared the 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 cotherapy 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: After prior therapeutic failure, 42 patients were on split-dose regimen (group A) and 20 patients were on thiopurine-allopurinol cotherapy (group B). Twelve patients crossed from group A to group B because of treatment failure, 1 patient was lost at follow-up, and 1 patient discontinued the treatment. The final cotherapy group comprised 29 children (group C), while the split-dose group (group D) included 31 children. Intention-to-treat analysis showed significant differences between split-dose regimen and thiopurine-allopurinol cotherapy for 6-thioguanine nucleotide (6-TGN)/6-methyl mercaptopurine (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 cotherapy ( P < 0.05). DISCUSSION: In children with IBD and impaired thiopurine metabolism, split-dose thiopurine and low-dose thiopurine-allopurinol cotherapy are both effective therapeutic strategies. The latter shows higher efficacy but a higher side effect rate, suggesting the use of split-dose regimen as the first-line approach. KEYWORDS: pediatric inflammatory bowel disease, thiopurines, split-dose thiopurine, low-dose azathioprine-allopurinol cotherapy

CITATION EXPORT

Lucia Cococcioni, Licia Pensabene, Maria Giovanna Puoti et al.. Safety and Efficacy of Split-Dose Thiopurine vs Low-Dose Thiopurine-Allopurinol Cotherapy in Pediatric Inflammatory Bowel Disease. Clinical and Translational Gastroenterology. (2022). https://doi.org/10.14309/ctg.0000000000000544

AUTHORS

10 · 3 CENTRES

Lucia Cococcioni, Licia Pensabene, Maria Giovanna Puoti, Sara El-Kouly, Sibongile Chadokufa, Raechel Buckingham, Edward Gaynor, Efstratios Saliakellis, Fevronia Kiparissi, Osvaldo Borrelli

1Gastroenterology Department, Great Ormond Street Hospital, London, UK;
2Paediatric Department, “V. Buzzi” Children's Hospital, University of Milan, Milan, Italy;
3Department of Surgical and Medical Sciences, Magna Graecia University, Catanzaro, Italy.