Paediatric patients with moderately to severely active ulcerative colitis (UC) show a favourable response to ustekinumab administered once every 4 weeks (Q4W), according to 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 observed that the steady state ustekinumab concentrations increased from 0.38 to 0.97 μg/mL, depending on whether 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 on whether 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 Q8 dosing at week 16, we observed 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 who had an inadequate response or were intolerant to prior treatment received a single open-label intravenous ustekinumab induction dose in the phase III, multicentre, interventional UNIFI Jr study.
At week 8, 109 patients were randomized 1:1 to blinded maintenance subcutaneous ustekinumab Q8W or Q12W for 44 weeks. De Greef and her team evaluated 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) transitioned to Q4W dosing in EOS. Four of 109 patients (3.7 percent) were induction nonresponders by week 16, and 17 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 previously failed biologic therapy, 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 of 13 patients (84.6 percent) achieved clinical response, and nine 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 initiation of Q4W dosing. After Q4 dosing, the 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).
Most patients (81 percent) reported experiencing adverse events (AEs), with infections being the most common (57.1 percent). A few 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 baseline in this EOS. It had higher serum ustekinumab concentrations in participants who had a loss of response after week 16 and in those 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. There were no new safety issues identified, no deaths, no cancers, and the rate of discontinuation was very low,” she added.
In the UNIFI programme, 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]