Among patients with Crohn disease (CD), approximately one-third of patients who receive ustekinumab require dose intensification during the first year of treatment, according to study results published in Digestive and Liver Disease.
This retrospective, observational study was conducted using data from the National Health Services (NHS) in Lothian, Scotland. Patients (N=163) with CD who received ustekinumab between 2015 and 2020 were evaluated for rates and risk factors for needing a dose intensification of ustekinumab treatment.
The study cohort comprised patients who had a median age of 23.0 (IQR, 22.4-29.3) years at diagnosis; 43.6% were men; median BMI was 24.9 (IQR, 22.4-29.3) kg/m2; they had had CD for 9.5 (IQR, 4.8-17.1) years prior to starting ustekinumab; 49.7% had nonstricturing, nonpenetrating disease; 47.9% had ileocolonic localized disease; 42.3% had undergone inflammatory bowel disease-related surgery; and 25.8% had previously received anti-tumor necrosis factor (TNF) and vedolizumab therapies.
At ustekinumab start, 79.1% received 8-weekly intervals and 20.9% 12-weekly intervals, 23.3% received concomitant steroids, and 12.3% concomitant immunosuppressants.
Stratified by requiring dose intensification to 4- or 6-weekly intervals (33.7%), more of the cohort who needed dose intensification started ustekinumab later in their disease course (P <.001), started at 8-weekly intervals (P =.002), and used concomitant steroids (P =.042) compared with those not requiring dose intensification.
The median time to dose intensification was 6.1 months and the indications for dose intensification were absence of steroid-free clinical remission (85.6%), biochemical disease activity of fecal calprotectin greater than 250 mg/g (65.5%) or C-reactive protein greater than 5 mg/l (61.8%), active disease at magnetic resonance imaging (49.1%), and/or active disease at endoscopy (14.5%).
Risk for dose intensification was assoicated with prior exposure to anti-TNF and vedolizumab (HR, 9.5; 95% CI, 1.3-70.9) and concomitant steroid use (HR, 1.8; 95% CI, 1.0-3.1).
After dose intensification, 14.5% achieved corticosteroid-free remission at week 16 compared with 27.0% for those who did not require intensification (P =.008). At year one, 51.1% of those without corticosteroid-free remission at intensification achieved remission.
Among the whole cohort, a total of 36.8% discontinued ustekinumab due to secondary loss of response (17.8%), primary nonresponse (15.3%), adverse events (2.5%), and due to rheumatological disease (1.2%).
The adverse event rate at baseline dosing was 8.3 per 100 person-year follow-up, including skin reactions, infections, arthralgia, headache, and cardiac failure events. The rate for dose-intensified ustekinumab dosing was 6.0 per 100 person-year follow-up and included infection and headache events.
The major limitation of this study was the proportion of missing data.
This study found that nearly one-third of patients with CD who received ustekinumab required dose intensification within the first year of treatment. Patients who had a history of multiple biologic treatment failures were more likely to require dose intensification.
“UST [ustekinumab] dose intensification appears to be effective, although firm conclusive data are still lacking,” the study authors noted.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Derikx LAAP, Plevris N, Su S, et al. Rates, predictive factors and effectiveness of ustekinumab intensification to 4- or 6-weekly intervals in Crohn’s disease. Dig Liver Dis. Published online October 22, 2022. doi:10.1016/j.dld.2022.10.002