4-week ustekinumab dosing revs up response in Crohn’s disease

For Crohn’s disease (CD) patients with suboptimal response to ustekinumab, doubling the dosing frequency from every 8 weeks to every 4 weeks elicited meaningful improvements in objective and patient-reported outcomes, as shown in a small retrospective study.

Following dose escalation, 91 percent of patients achieved improvement in at least one disease parameter, reported Dr Vikash Sagar and colleagues from Frimley Health NHS Foundation Trust in the UK. [AIBD 2025, abstract 96]

Small bowel imaging results at 12 months showed disease improvement in 67 percent of patients; 24 percent of patients had stable disease, while 10 percent experienced worsening. Objective motility scores incorporated into MR enterography improved in 83 percent of patients (median GIQuant scores, 76–119).

Reductions in inflammatory markers such as C-reactive protein (CRP) and faecal calprotectin (FC) were seen in 70 percent and 80 percent of patients, respectively. Simple Endoscopic Score for CD (SES-CD) also improved.

In terms of patient-reported outcomes, 55 percent reported improvements, while 36 percent reported no change. The remaining 9 percent of patients were persistently asymptomatic.

No adverse events were documented during throughout the study.

The analysis included 23 CD patients (median age 47 years, 57 percent female) at Frimley Health NHS Foundation Trust who underwent ustekinumab dose escalation from every 8 weeks to every 4 weeks. The median time to escalation was 16 months.

According to Montreal classification, 35 percent had L1 disease, 9 percent had L2 disease, and 57 percent had L3 disease at baseline. A total of 22 percent of patients had perianal disease.

The data from this real-world cohort are in line with those reported in small prospective studies, according to Sagar and colleagues.

“With the advent of biosimilar ustekinumab, interval escalation should be considered a viable and cost-conscious alternative to biologic switching in selected CD patients,” they added.

Ustekinumab as good as anti-TNF drugs

In a separate study, the clinical and endoscopic effectiveness of ustekinumab in CD patients were comparable to that of anti-tumour necrosis factor (anti-TNF) agents, regardless of prior biologic exposure.

In a real-world cohort of patients with moderately-to-severely active CD initiating first- or second-line biologic therapy, clinical remission rates at week 52 were 77.6 percent with ustekinumab vs 72 percent with anti-TNF for biologic-naïve patients (p=0.57) and 55.6 percent vs 47.6 percent, respectively, for those with prior biologic failure (p=0.52). [AIBD 2025, abstract 112]

Steroid-free clinical remission rates were likewise similar between ustekinumab and anti-TNF: 63.1 percent vs 65.8 percent, respectively, in the biologic-naïve subcohort (p=0.42) and 57.1 percent vs 44.7 percent in the biologic-failure subcohort (p=0.36).

Endoscopic remission occurred in a similar number of ustekinumab-treated and anti-TNF–treated patients both in the biologic-naïve subcohort (70.7 percent vs 67.2 percent, respectively; p=0.36) and the biologic-failure subcohort (37.8 percent vs 40.8 percent, respectively; p=0.38). No significant between-group difference was observed in clinical response and biochemical remission at week 52.

Among patients with biologic-failure, ustekinumab was significantly associated with a significantly lower rate of secondary loss of response (13.8 percent vs 23.7 percent; p=0.006) and fewer serious adverse events (12.5 percent vs 28.3 percent; p<0.01) compared with anti-TNF.

Among those who were biologic-naïve, treatment persistence was significantly greater with ustekinumab vs anti-TNF (96.9 percent vs 80.8 percent; p=0.029), and this was accompanied by reduced relapse rates (3.1 percent vs 11.1 percent; p=0.01).

The analysis included 530 CD patients, of whom 226 initiated ustekinumab, 172 initiated infliximab, and 132 initiated adalimumab. Primary endpoints were clinical remission (HBI Harvey-Bradshaw Index ≤4), endoscopic remission (SES-CD ≤3 or Rutgeerts score i0 or i1), and steroid-free clinical remission at week 52.

Overall, the findings demonstrate the viability of ustekinumab as a first- or second-line biologic option in the management of CD, according to the authors.