Among patients with moderate to severe Crohn disease (CD), who are biologic-naïve, both ustekinumab and adalimumab monotherapy were highly efficacious, according to study results published in The Lancet.
Researchers conducted a randomized, double-blind, parallel-group, active-comparator, phase 3b trial, called SEAVUE (ClinicalTrials.gov Identifier: NCT03464136), at 121 hospitals in 18 countries. Patients (N=386) who had moderate to severe CD and were biologic-naïve were randomly assigned 1:1 to receive 6 mg/kg intravenous ustekinumab on day 0 and week 2, followed by 90 mg subcutaneous ustekinumab every 8 weeks (n=191) or 160 mg subcutaneous adalimumab on day 0, 80 mg subcutaneous adalimumab at week 2, and 40 mg subcutaneous adalimumab every 2 weeks (n=195). The trial lasted for 56 weeks, and both groups received appropriate placebo injections to blind patients and clinicians to the study group.
The primary endpoint was the proportion of patients achieving clinical remission at week 52, defined as Crohn’s Disease Activity Index (CDAI) lower than 150.
The ustekinumab and adalimumab cohorts were 53% and 51% women; had a mean age of 37.0±13.23 and 37.4±12.99 years; 86% and 93% were White; the median duration of disease was 2.6 (IQR, 0.7-5.8 and 2.6 IQR, 0.9-8.6) years; 54% and 53% had disease activity in the ileum and colon; and median CDAI score was 287.0 (IQR, 253-348) and 291.0 (IQR, 257-330), respectively.
At week 52, the primary outcome was reached by 65% of the ustekinumab and 61% of the adalimumab recipients (between group difference, 4%; 95% CI, -6% to 14%; P =.42).
The ustekinumab and adalimumab cohorts associated with similar corticosteroid-free clinical remission (61% vs 57%), clinical response (72% vs 66%), and Patient Reported Outcome-2 (PRO-2) symptom remission (57% vs 55%) rates at week 52 and clinical remission at week 16 (57% vs 60%), respectively.
Ustekinumab associated with significantly greater improvement in the sum of the number of stools and abdominal pain scores during the previous 7 days compared with baseline (mean change, -29.6 vs -25.1; P =.013) and maintenance of response obtained during induction (between group difference, 11%; 95% CI, 2%-19%; P =.016).
Treatment was discontinued early by 15% of the ustekinumab and 24% of the adalimumab cohorts. The most common motivations for discontinuation included adverse events (6% vs 11%), withdrawal of consent (6% vs 5%), and lack of improvement (2% vs 5%), respectively. Ustekinumab was associated with significantly greater treatment retention (P =.047).
Adverse events occurred among 80% of the ustekinumab and 78% of the adalimumab cohorts. The most frequent treatment-emergent events included CD event (12% vs 16%), nasopharyngitis (7% vs 10%), abdominal pain (13% vs 8%), and headache (12% vs 7%), respectively.
The findings of this study may not be generalizable for patients with previous exposure to biologic therapy or those with longer duration of disease.
This study found evidence that both ustekinumab and adalimumab monotherapies associated with high rates of clinical remission among patients with CD who were biologic-naïve. Although ustekinumab outperformed adalimumab for some outcomes, it did not meet the criteria for superiority.
“The results of this study support the use of safe and effective biologic agents for patients with moderately to severely active Crohn’s disease early in the disease course and reinforce the need for direct active-comparator studies for inflammatory bowel disease treatment, rather than indirect comparisons,” 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.
Sands BE, Irving PM, Hoops T, et al. Ustekinumab versus adalimumab for induction and maintenance therapy in biologic-naive patients with moderately to severely active Crohn’s disease: a multicentre, randomised, double-blind, parallel-group, phase 3b trial. Lancet. 2022;399(10342):2200-2211. doi:10.1016/S0140-6736(22)00688-2