One-year Outcomes With Ustekinumab Therapy in Infliximab-refractory Paediatric Ulcerative Colitis

A Multicentre Prospective Study

Jasbir Dhaliwal; Hayley E. McKay; Colette Deslandres; Jennifer Debruyn; Eytan Wine; Ashley Wu; Hien Huynh; Nicholas Carman; Eileen Crowley; Peter C. Church; Thomas D. Walters; Amanda Ricciuto; Anne M. Griffiths


Aliment Pharmacol Ther. 2021;53(12):1300-1308. 

In This Article

Abstract and Introduction


Background: The phase 3 (UNIFI) trial of ustekinumab (anti-interleukin 12/23) demonstrated efficacy even after prior biologic failure in adult ulcerative colitis (UC), but paediatric data are lacking.

Aim: To prospectively monitor efficacy and serum concentrations of ustekinumab given to children with UC refractory to other biologics.

Methods: Children with anti-TNF refractory UC initiating ustekinumab intravenously at sites of the Canadian Children IBD Network prior to 12/2019 are included. The primary endpoint was steroid-free clinical remission with subcutaneous ustekinumab at 52 weeks (Paediatric Ulcerative Colitis Activity Index <10, no steroids ≥4 weeks). Ustekinumab levels were measured after week 20. Endoscopic improvement was defined as Mayo endoscopic subscore ≤1, or faecal calprotectin (FCP) <250 μg/g if not re-colonoscoped.

Results: At six sites between 01/2018 and 11/2019, 25 children (median [IQR] age 14.8 years [12.3–16.2], 72% female) with UC duration 2.3 years (1.1–4.2) received intravenous ustekinumab (median dose/kg of 6.4 [5.5–7.5] mg). All patients had failed prior infliximab therapy, and 12 (48%) also vedolizumab. Five patients discontinued ustekinumab after IV induction (four undergoing colectomy). On intent to treat basis, 44% achieved the primary endpoint of steroid-free remission at week 52, including nine (69%) of 13 who previously treated with anti-TNF only vs two (17%) of 12 who previously failed also by vedolizumab (P = 0.008). Seven of 11 remitters met the criteria for endoscopic improvement. The median (IQR) trough levels (μg/mL) were greater with q4 vs q8 weekly dosing (8.7 [4.6–9.9] vs 3.8 [12.7–4.8]) P = 0.02, but greater exposure was not associated with a superior rate of clinical remission. No adverse events were associated with therapy.

Conclusion: Ustekinumab demonstrated efficacy in this paediatric cohort with otherwise treatment-refractory UC. Treatment failure was not due to inadequate drug exposure.


Ulcerative colitis (UC) is a disabling disease characterised by chronic inflammation of the colon. UC developing in children and adolescents poses particular challenges, given the predominance of extensive colonic involvement in young patients,[1,2] their long lives ahead during which complications of uncontrolled inflammation, including colon cancer, may occur,[3] and uniquely among those yet to reach their adult height, the potentially detrimental effects of chronic corticosteroids on linear growth. As documented in the PROTECT study, paediatric UC is often unsatisfactorily controlled by "conventional" medical therapies.[4] Infliximab, the anti-tumour necrosis factor (TNF) agent most often used in children with UC, has constituted a significant advance in treatment, but at least one-third of patients exhibit primary non-response, highlighting a clear need for alternate pathway biologics or oral small molecule therapies.[5,6]

Ustekinumab, a fully human IgG1 monoclonal antibody targeting the interleukin (IL)I2/IL23 shared p40 subunit, was found to be efficacious in adults with moderate to severe UC in the phase III randomised, double-blind, placebo-controlled, parallel-group UNIFI trial (UNIFI NCT02407236), which included patients with prior anti-TNF failure.[7] When the UNIFI trial results were first made public, ustekinumab began to be administered off-label to paediatric patients with UC and prior anti-TNF failure enrolled in the Canadian Children IBD Network (CIDsCANN). Outcomes were prospectively monitored.

The aim of the study was to examine the efficacy of ustekinumab in achieving corticosteroid-free clinical remission at week 52 in children with colitis failed by prior biologics. Therapeutic drug monitoring (TDM) was utilised in order to provide novel data concerning dosing and drug exposure in young patients.