Paediatric patients with moderately to severely active ulcerative colitis (UC) show a favourable response to ustekinumab administered once every 4 weeks (Q4W), reports a study. This results in greater clinical response and remission associated with higher serum drug levels.
“Following the Q4W dosing in the exposure optimization study (EOS), we could see that the steady state ustekinumab concentrations increased from 0.38 to 0.97 μg/mL, depending if we look at the median or the mean at week 0,” said lead study author Dr Elisabeth De Greef, Department of Paediatric Gastroenterology and Nutrition, KidZ'Health Castle, UZ Brussels, Brussels, Belgium.
“And they go up to 2.28 or 3.75, depending if you look at the median or mean at week 16… That is actually very similar to what we see in the adult study where at the Q8 dosing at week 16, we could see median and mean concentrations of 2.69 and 3.28 μg/mL,” she added.
A total of 112 paediatric patients (aged 2 to <18 years) with moderate-to-severe UC and inadequate response/intolerance to prior treatment received one open-label intravenous ustekinumab induction dose in the phase 3, multicentre, interventional UNIFI Jr study.
At week 8, 109 patients were randomly allocated in a 1:1 ratio to blinded maintenance subcutaneous ustekinumab Q8W or Q12W for 44 weeks. De Greef and her team evaluated the participants at week 15 for clinical response (partial Mayo score) and clinical remission (PUCAI score).
Ninety-seven of the 109 patients responded to treatment, and 21 (19.3 percent) went to Q4W dosing in EOS. Four out of 109 patients (3.7 percent) were induction nonresponders by week 16, and 17 out of 97 participants (17.5 percent) had loss of response and low ustekinumab levels during the maintenance period. [ESPGHAN 2026, abstract OP019]
Q4W dosing
Of the 21 patients who received Q4W dosing, 12 (57.1 percent) had failed biologic therapy in the past, and all (100 percent) had extensive colitis. Twelve (57.1 percent) and 16 (76.2 percent) participants also had elevated C-reactive protein and faecal calprotectin, respectively.
Furthermore, 16 (76.2 percent) patients completed the 16-week EOS, 11 out of 13 patients (84.6 percent) achieved clinical response, and nine out of 16 (56.3 percent) achieved clinical remission.
“Average PUCAI scores and partial Mayo scores from initiation of EOS decreased over time,” wrote De Greef and colleagues.
The mean serum ustekinumab concentration in paediatric patients was 0.38 µg/mL prior to the administration of the Q4W dosing. Such concentration rose to within the range observed in adults with UC receiving 90 mg Q8W (serum trough concentrations ranged from 0.87‒7.18 µg/mL at substudy week 12 in UNIFI Jr) after the Q4W dosing.
Most of the patients (81.0 percent) reported experiencing adverse events (AEs), with infections being the most common (57.1 percent). A few of them had serious AEs. The safety profile of subcutaneous ustekinumab Q4W dosing was consistent with the main study.
“[T]his data shows us quite nicely that ustekinumab Q4W dosing led to an increase in clinical response and remission from the baseline in this EOS. It had higher serum ustekinumab concentrations for the participants who had a loss of response after week 16 and the participants who had a nonresponse at week 16 with low trough levels,” De Greef said.
“We see that we could increase the ustekinumab concentration and that it was associated with an improved PUCAI score. And there were no new safety issues identified, no deaths, no cancers, and the rate of discontinuation was very low,” she added.
In the UNIFI program, treatment with ustekinumab induced and maintained response and remission in adult patients with moderate-to-severe UC. [N Engl J Med 2019;381:1201-1214]
“Data from the UNIFI study demonstrated that [the] minimum 8-week steady-state serum trough concentrations of ustekinumab ≥1.3 μg/mL were associated with clinical remission,” De Greef said. [Clin Gastroenterol Hepatol 2020;18:2244-2255]