Mallory Chavannes1,2, Christine Martinez-Vinson3, Lara Hart4, Nicole Kaniki5, Che-Yung Chao4,6, Sally Lawrence7, Kevan Jacobson7, Jean-Pierre Hugot3, Jérome Viala3,8, Colette Deslandres1,9, Prevost Jantchou1,9, Ernest G Seidman4. 1. Department of Paediatrics, Sainte-Justine UHC, University of Montreal, QC, Canada. 2. Department of Paediatrics, Children Hospital of Los Angeles, Los Angeles, CA, USA. 3. Division of Paediatric Gastroenterology, Hôpital Robert-Debré, Assistance Publique-Hôpitaux de Paris, Paris, France. 4. Montreal Children's Hospital, Department of Paediatrics, McGill University, Montreal, QC, Canada. 5. Research Western, Western University, London, ON, Canada. 6. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, QLD, Australia. 7. Division of Paediatric Gastroenterology Hepatology and Nutrition, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada. 8. UFR de Médecine, Université Paris Diderot-Sorbonne Paris Cité, Paris, France. 9. Research Centre of CHU Sainte-Justine, University of Montreal, Montreal, QCc, Canada.
Abstract
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 (χ2[1] = 42.7, p = 1.2 × 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.
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 (χ2[1] = 42.7, p = 1.2 × 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.
Authors: Gala M Godoy Brewer; George Salem; Muhammad A Afzal; Berkeley N Limketkai; Zadid Haq; Maryam Tajamal; Joanna Melia; Mark Lazarev; Florin M Selaru; Alyssa M Parian Journal: BMJ Open Gastroenterol Date: 2021-12