Experience Using Ustekinumab in Pediatric Patients With Medically Refractory Crohn Disease

Abstract

Introduction:Ustekinumab (UST), a human monoclonal antibody against interleukin-12 and 23, is approved to treat adult patients with psoriasis or Crohn disease (CD). Outcomes data for off-label use in pediatric patients with CD are limited.Aim:We conducted a retrospective cohort study to analyze the long-term efficacy of UST, including dose adjustments, in the treatment of pediatric patients with medically refractory CD. Adverse events were documented.Methods:We identified 40 pediatric patients with CD treated with UST between January 1, 2016 and December 31, 2019. Electronic medical records were reviewed for demographics, Paris Classification, significant comorbidities, previous CD therapy, adverse events after initiation, and surveillance markers at the time of their first dose and most recent clinic visit. A validated abbreviated pediatric CD activity index (aPCDAI) was used to assess response to therapy.Results:Thirty-eight pediatric patients with CD, including 34.2% with stricturing or penetrating disease, were analyzed after initiation of treatment with UST. Median age at diagnosis of CD was 12.5 years, and median age at UST induction was 17.2 years. No patients were anti-TNF-naive, and 34.2% were previously exposed to 2 or more anti-TNF agents. At time of last follow-up, 84.2% of patients remained on UST for a median duration on UST of 62.1 weeks, and 60.5% achieved clinical remission. Patients had significant improvement in aPCDAI scores, clinical remission rates, albumin, and hematocrit, and 89.5% of patients had no significant adverse events. Similar results were observed among those who required dose adjustment, including 61.1% achieving clinical remission, and among those with perianal disease, including 38.5% achieving clinical remission.Conclusions:Our data suggest that, within our cohort of pediatric patients with CD, UST has long-term efficacy with no observed safety concerns. Dose adjustment may be helpful in achieving clinical remission.

Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN

“…Moreover, the wPCDAI, the CRP, and FC levels decreased significantly. These results are in line with those of Kim et al (14) who studied the largest real-life pediatric cohort published to date. They reported a decline of abbreviated PCDAI from 25 to 5 and an increase in the clinical remission rate from 11% to 61%.…”

Real-World Evidence of the Effectiveness and Safety of Ustekinumab for the Treatment of Crohn’s Disease: Systematic Review and Meta-Analysis of Observational Studies

“…A total of 63 studies (including 8529 patients) met the inclusion criteria and were finally included in the systematic review and meta-analysis ( Figure 1 ) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , ...…”

“…Only one study focused exclusively on naïve patients [ 55 ], and in three studies, prior biologic exposure was not reported. Only three studies (4.8%) included paediatric patients [ 54 , 59 , 63 ] ( Table 1 ).…”

New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease

“…Some case reports suggest that 50% of children with IBD have a clinical response to ustekinumab ( 94 , 95 ). In a cohort of pediatric patients with CD, patients using ustekinumab had significant improvements in their abbreviated pediatric CD activity index (aPCDAI) scores, clinical remission rates, albumin, and hematocrit, and 89.5% of patients had no significant adverse events ( 96 ). The use of off-label drugs is increasing in children with IBD and generally they are being reported as safe and effective ( 93 ).…”