Two-thirds of patients with inflammatory bowel disease (IBD) treated at an IBD centre in Singapore required dose intensification (DI) while on ustekinumab, with 38.1 percent of them achieving disease remission at 1 year, as shown in a retrospective observational study.
“To our knowledge, this is the first study on the effectiveness of DI and persistence of ustekinumab in a Southeast Asian population,” said lead author Dr Chong-Teik Lim from the Department of Gastroenterology and Hepatology, Singapore General Hospital (SGH), Singapore.
Lim and colleagues identified adult patients who were started on ustekinumab for Crohn's disease (CD) or ulcerative colitis (UC) at the IBD Centre of SGH between September 2017 and October 2022. During the study period, 63 patients were initiated on ustekinumab, 42 (66.7 percent) of whom had DI from 90 mg every 8 weeks to 90 mg every 6 or 4 weeks. [J Gastroenterol Hepatol 2024;doi:10.1111/jgh.16562]
Disease aggressiveness predicts DI
In the overall cohort (median age 37 years, 58.7 percent male), the majority had CD (82.5 percent), while 76.2 percent had failed ≥1 biologic before, and 39.7 percent had a history of IBD-related surgery.
After a median of 7.2 months, 65.4 percent of patients with CD and 72.7 percent of those with UC had ustekinumab DI. The most common indication for DI was suboptimal clinical response to standard ustekinumab dosing (42.9 percent).
Crude Cox regression analysis showed that younger age at diagnosis (p=0.03) and number of prior biologics used (p=0.03) were significant predictors of DI. The presence of perianal disease (p=0.005) was an additional predictor of DI within the CD cohort, whereas the number of prior biologics used was not.
Among the patients who had DI, 38.1 percent achieved disease remission (CD cohort: 38.2 percent; UC cohort: 37.5 percent) by week 52, defined based on clinical, biochemical, endoscopic, and transmural criteria. The provision of ustekinumab re-induction was not associated with the achievement of disease remission (p=0.51 on univariate analysis).
Prudent to wait longer
A significant reduction in C-reactive protein (CRP) levels was observed among patients without DI as early as 3 months, but this was not the case among patients with DI (p=0.209 at 3 months). A statistically significant CRP response was only noted after 6 months following DI (p=0.018).
Lastly, undergoing DI did not materially modify the 1-year drug persistence rate (with DI, 73.5 percent vs without DI, 80.4 percent; log-rank p>0.05).
Ustekinumab received regulatory approval from the Health Sciences Authority in Singapore in February 2018 for the treatment of CD. [Intest Res 2022;20:291-296] For both the CD and UC indications, the labelled dosage consists of a single intravenous induction dose, followed by a 90-mg subcutaneous (SC) dose 8 weeks later, and a maintenance dose of 90 mg SC every 8 or 12 weeks (Q8W or Q12W).
In the IM-UNITI trial of ustekinumab maintenance in CD, a dose adjustment to 90 mg Q8W in patients who had lost clinical response on 90 mg Q12W resulted in 41.4 percent of patients achieving clinical remission, suggesting a benefit from DI. [N Engl J Med 2016;375:1946-1960] However, suboptimal or loss of response to the Q8W maintenance dose has been observed in practice, prompting consideration of DI to even shorter dosing intervals. [Aliment Pharmacol Ther 2020;52:135-142; Inflamm Bowel Dis 2024;doi:10.1093/ibd/izae058]
“Biochemical response in dose-intensified patient appeared to be delayed up till 6 months after DI and from this study, it may be prudent to wait longer for response prior to deciding on newer medications,” concluded Lim.