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P03 Leflunomide treatment for inflammatory bowel disease and intestinal failure caused by TTC7A deficiency
  1. Emma Williams
  1. Cambridge University Hospitals NHS Foundation Trust


TTC7A deficiency Ultra-rare autosomal-recessive variants in tetratricopeptide repeat domain 7A gene (TTC7A) have been discovered in patients presenting with severe intestinal disease. Mutations in the TTC7A gene cause intestinal epithelial and immune defects resulting in apoptotic enterocolitis, multiple intestinal atresia, and recurrent intestinal stenosis. Patients face high mortality rates with palliation as the current standard of care.1

Leflunomide In 2020 a high throughput screen identified drugs that increased cell viability in patients with TTC7A; leflunomide reduced caspase 3 and 7 (responsible for cell death) activity in cells by 96%. In zebrafish with disruption of TTC7A, leflunomide restored gut motility, reduced intestinal tract narrowing, and increased intestinal cell survival.1 From a literature review, only 3 patients in the world have been prescribed leflunomide for TTC7A deficiency with ‘encouraging results’.2 however no case reports have been completed on treatment safety or effectiveness.

A common adverse effect of leflunomide is liver toxicity due to production of a toxic intermediate; however, the reaction appears to be idiosyncratic and unpredictable.3 Full blood count and liver function tests must be checked before initiation of leflunomide, every two weeks during the first six months of treatment, and every 8 weeks thereafter.4

The patient A 7-year-old male on home parenteral nutrition with TTC7A deficiency was admitted to hospital with high ileostomy output and persistent vomiting with a background of mucosal gastrointestinal inflammation and pyloric stenosis. On behalf of the gastroenterology team, the paediatric gastroenterology pharmacist applied for urgent internal funding and clinical governance approval for leflunomide treatment with the aim to ameliorate intestinal disease. Leflunomide 10 mg daily costs £3.11/month. Treatment was approved, the patient and his family were counselled by the pharmacist and the patient began treatment of leflunomide 10 mg via PEG tube daily.

Adverse event After two weeks of treatment the patient’s alkaline phosphate (ALP) and Gamma GT (GGT) had doubled and their alanine transaminase (ALT) had increased 10-fold. Advice from the pharmacist was sought. On review of the leflunomide summary of product characteristics4: ‘Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide//If ALT elevations of more than 3-fold the upper limit of normal are present, leflunomide must be discontinued and wash-out procedures initiated.’ A decision was made to stop treatment, however a washout procedure with cholestyramine or activated charcoal was not possible as the patient had minimal oral intake due to vomiting. The pharmacist filed a yellow card report.

Follow up The patient’s ALT normalised after 3 weeks and GGT after 2 months of treatment cessation. It took 8 months for the patient’s ALP to normalise.

Lessons learnt Unfortunately, it was impossible to assess the potential gastrointestinal benefits of leflunomide in this patient due to the rapid onset of significant liver toxicity. Liver toxicity may have been identified sooner if a blood test was taken 1 week after treatment initiation. Monitoring liver function earlier following initiation of leflunomide treatment may be helpful to minimise liver toxicity in patients with TTC7A deficiency.


  1. Jardine S, Anderson S, Babcock S, et al. Drug screen identifies leflunomide for treatment of inflammatory bowel disease caused by TTC7A deficiency. Gastroenterology 2020;158:1000–1015.

  2. Cerretani J. Going ‘all in’ for Khori: new hope for congenital enteropathy [Internet]. Boston Children’s Hospital, 2020. [accessed May 2022]. Available from:

  3. Nuray Aktay A, Gul Karadag S, Cakmak F, et al. Leflunomide in juvenile rheumatoid arthritis. Future Rheumatol 2006;1(6):673–682.

  4. Electronic Medicines Compendium [Internet]. Leflunomide 10 mg film-coated tablets, 2017 [cited May 2022]. Available from:

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