Is long-term ustekinumab safe and effective in children with Crohn’s disease?

Use of ustekinumab for up to 4 years in paediatric patients with Crohn’s disease (CD) shows similar efficacy, safety, pharmacokinetics (PK), and immunogenicity to that seen in adult patients, according to the results of the UniStar study long-term extension.

Finding of UniStar, a phase I, multicentre, double-blind study in paediatric patients (2‒18 years; body weight ≥10 kg) with moderate-to-severe active CD, was presented at the recent DDW 2023 in Chicago, Illinois, US.

The investigators stratified 45 patients by body weight (<40 or ≥40 kg) and randomized them to low- (<40 kg: 3 mg/kg; ≥40 kg: 130 mg) or high-dose (<40 kg: 9 mg/kg; ≥40 kg: 390 mg) intravenous ustekinumab. Patients then received one subcutaneous maintenance dose (<40 kg: 2 mg/kg; ≥40 kg: 90 mg) at week 8.

Children with CD who responded to treatment at week 14 were included in the long-term extension and continued ustekinumab maintenance dosing every 8 weeks up to week 268. The investigators assessed the efficacy, safety, PK, and immunogenicity at weeks 16, 24, 48, 224, and through 240 weeks as applicable. Week 48 was the primary visit, representing outcomes after nearly 1 year of treatment.

Of the patients, 34 (77 percent; median age 13.0 years, 62 percent female, 47 percent weighed <40 kg, 18 percent <30 kg) responded to treatment and entered the extension phase of the study. Nearly all (94 percent) previously failed antitumour necrosis factor therapy. [DDW 2023, abstract 2009]

The number of children who received ustekinumab at weeks 48, 104, 152, and 208 was 26 (77 percent), 16 (47 percent), 12 (35 percent), and eight (24 percent), respectively. At week 48, 14 children (41 percent) achieved clinical remission and 20 (59 percent) achieved clinical response.

Twenty-four patients (71 percent) presented with abnormal C-reactive protein (CRP) levels at baseline, but 16 of 27 (59 percent) achieved normalization of CRP (<3 mg/L) at week 48.

The visit at week 240 saw 91 percent of patients reporting at least one adverse event (AE) and 15 percent ceasing treatment due to AEs, with CD worsening as the most common cause. Serious AEs occurred in 32 percent of children and infections in 74 percent. Most serious AEs were gastrointestinal disorders. No injection-site reactions, serious infections, malignancies, or deaths occurred.

“Median serum ustekinumab concentrations tended to be lower in patients weighing <40 kg compared with [those] weighing ≥40 kg but were generally consistent from weeks 16 to 268 and remained detectable through week 200,” the investigators said. “Incidence of ustekinumab antibodies was low (one out of 34; 3 percent).”

A separate study presented at DDW 2023 reported the association of higher maintenance ustekinumab trough levels (UTL) with sonographic transmural healing (TH) in children with inflammatory bowel disease (IBD). TH assessed by intestinal ultrasound is associated with improved IBD outcomes. [DDW 2023, abstract 1996]

Ustekinumab is a biologic therapy approved for the treatment of adults with CD. A recent study demonstrated high rates of efficacy, low rates of immunogenicity, and safety of ustekinumab in paediatric patients similar to that observed in adults through 16 weeks. [J Crohns Colitis 2021;15:1931]