High‐dose azathioprine in children with inflammatory bowel disease

Abstract

Summary Background: Azathioprine is widely used as maintenance therapy in children with moderate to severe inflammatory bowel disease (IBD). There is no data on safety at higher doses and its impact on growth and surgical morbidity in children. Methods: This retrospective cohort study included all children treated with azathioprine and diagnosed with IBD between 1996–2001. Outcome measures included indications for azathioprine use, adverse‐effects and reasons for treatment discontinuation. Height and weight at diagnosis, treatment onset and current follow‐up was recorded, and Z scores for height standardised for time. Results: 107 children received azathioprine at 3 mg/kg. 61% had Crohn's disease and 83% started azathioprine within 2 years of diagnosis. Only 2/107 children had to stop azathioprine because of persistent adverse effects and 16/107 required surgery. There was a trend toward better growth in a group of children with Crohn's disease following treatment with high dose azathioprine therapy (P = 0.08). Conclusions: Azathioprine is a safe and well‐tolerated maintenance therapy at 3 mg/kg for children with IBD. The prevalence of surgery and growth failure in a cohort of children with moderate to severe IBD appears less than previously reported. In children with Crohn's disease, growth velocity may be maximised by an emphasis on nutritional therapy and the use of high dose azathioprine.

Impact of Disease and Treatments on Growth and Puberty of Pediatric Patients with Inflammatory Bowel Disease

“…Indeed, and to the best of our knowledge, only one study adequately assessed the effect of azathioprine/6-MP on growth. Fuentes et al [74] retrospectively assessed growth in 107 children with IBD (CD and UC) treated with high-dose azathioprine (3 mg/kg instead of the usual 2–2.5 mg/kg). Only 10% of children had significant growth retardation (height z-score <–1.64) at time of diagnosis and 36% of the 57 children with CD maintained or improved their height z-score on follow-up.…”

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease

“…Use of AZA in pediatric CD patients in Europe was associated with a longer maintenance of first remission compared with nonuse of AZA 200. AZA at a high dose of 3 mg/kg was shown to be safe and well-tolerated maintenance therapy for children with CD 201. For children refractory to or intolerant of thiopurines, MTX can effectively maintain remission 202.…”

“…For children refractory to or intolerant of thiopurines, MTX can effectively maintain remission 202. The effect on growth velocity from treatment with immunomodulators is unclear and emphasis should be put on nutritional therapy to maximize growth 201202…”

Impact of Therapeutic Strategies on Growth in Pediatric Inflammatory Bowel Disease

“…This study is limited by small sample size and relatively high number of withdrawals from the placebo arm. Nevertheless, it seems that the use of azathioprine/6-MP is associated with only minimal effect on growth if any [100]. Methotrexate (MTX) is a therapeutic alternative for children with CD either as first line maintenance treatment or for children unresponsive or intolerant to thiopurines.…”