Management of Paediatric Patients With Medically Refractory Crohn's Disease Using Ustekinumab: A Multi-Centred Cohort Study

Background: Ustekinumab [UST] is effective in the treatment of adults with moderate to severe Crohn's disease [CD]. There is a paucity of data on its use in children. Aim: To evaluate the response to UST in children with moderate to severe CD. Methods: This multicentre retrospective cohort study identified children under 18 years old with CD, who received open-labelled subcutaneous UST. The primary outcome was changes in mean abbreviated Paediatric Crohn's Disease Activity Index [aPCDAI] between baseline and 3 and 12 months, and rate of clinical remission at 3 and 12 months. Secondary outcomes were clinical response at the same time points, changes in C-reactive protein [CRP] and albumin, improvement in growth parameters, and rate of adverse events. Results: A total of 44 patients who failed at least one biological treatment were identified. Linear mixed model [LMM] analysis revealed a statistically significant effect of UST (X2[1] = 42.7, p = 1.2 x 10(-8)) which lowered the aPCDAI scores by about 16 +/- 2.7 at 3 months, and 19.6 +/- 2.9 at 12 months. At 12 months, 38.6% of the patients achieved clinical remission and 47.8% achieved clinical response. There was a significant increase in mean weight z-score of 0.48 [+/- 0.13] [p < 0.001] and in mean body mass index [BMI] z score of 0.66 [+/- 0.16] [p < 0.001]. The probability of remaining on UST at 12 months was 76.9%. The rate of adverse events was 12.4 per 1000 patient-months. Conclusions: Subcutaneous UST should be considered a viable therapeutic option for paediatric patients who are refractory to other biological agents. Prospective randomised trials are needed.