SEAVUEMust knowCD · Head-to-head
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
Sands BE, et al.
Lancet 2022 · PMID 35691323 (PubMed, opens in a new tab) · doi 10.1016/S0140-6736(22)00688-2 (full paper, opens in a new tab)
| Outcome | Ustekinumab | Adalimumab | Estimate (confidence interval) | P |
|---|---|---|---|---|
| Clinical remission, Primary endpoint · CDAI below 150, week 52 (primary) | 124/191 (65%) | 119/195 (61%) | +4 (95% CI −6 to 14) | P=0.42 |
SEAVUE was a superiority trial: an interval that crosses zero means no difference was shown, not that the drugs are proven equivalent.
Source: Sands 2022, abstract (intention to treat).
Structured abstract
BackgroundUstekinumab and adalimumab were both first-line biologic options for Crohn's disease, but they had not been compared directly; choices relied on indirect comparisons of placebo-controlled trials.
MethodsPhase 3b, randomised, double-blind, parallel-group, active-comparator trial (121 sites, 18 countries). 386 patients. Primary endpoint: Clinical remission (CDAI below 150) at week 52.
ResultsPrimary result. 65% (124/191) with ustekinumab vs 61% (119/195) with adalimumab; difference 4% (95% CI −6 to 14); P=0.42.
Take-homeIn biologic-naive moderate-to-severe Crohn's disease, ustekinumab was not superior to adalimumab monotherapy at 1 year and both worked well, so choose by patient factors, safety and preference.
| Patients | 386 |
|---|---|
| Population | Biologic-naive adults with moderately to severely active Crohn's disease (CDAI 220–450) who had failed or were intolerant of conventional therapy (or were steroid-dependent), with at least one ulcer at baseline endoscopy. |
| Comparison | Ustekinumab vs adalimumab monotherapy at label doses |
| Drugs | ustekinumab, adalimumab |
| Classes | Anti-IL-12/23, Anti-TNF |
| Published | Sands BE, et al. Lancet 2022;399:2200–11. |
Key points
- Ustekinumab about 6 mg/kg IV, then 90 mg SC every 8 weeks; adalimumab 160 mg, 80 mg at week 2, then 40 mg SC every 2 weeks; through week 56.
- Discontinuation of study treatment before week 52: 15% (29/191) ustekinumab vs 24% (46/195) adalimumab.
- Serious infections: 2% (4/191) ustekinumab vs 3% (5/195) adalimumab; no deaths through week 52.
- No immunomodulator and no dose escalation were allowed in either arm, so this compares the drugs as monotherapy at label doses.
- Both drugs were highly effective in biologic-naive patients, with about 6 in 10 in clinical remission at week 52.
Limitations
- No dose optimisation and no concomitant immunomodulator, which is not how adalimumab is often used.
- Biologic-naive patients only.
- Not powered for endoscopic endpoints.
- Industry funded (Janssen Scientific Affairs).
Commentary
SEAVUE was the first head-to-head biologic trial in Crohn’s disease. It showed no meaningful efficacy difference between an anti-TNF and ustekinumab as first-line monotherapy. In practice the choice depends on factors such as perianal disease (more anti-TNF data), extraintestinal manifestations, infection or malignancy history, route and frequency of dosing, and drug-plan coverage.
The next question, which drug to use after anti-TNF failure, was addressed by SEQUENCE.
Journal club
Design
Phase 3b, randomised, double-blind, parallel-group, active-comparator trial (121 sites, 18 countries). 386 patients.
Primary result. 65% (124/191) with ustekinumab vs 61% (119/195) with adalimumab; difference 4% (95% CI −6 to 14); P=0.42.
Validity and applicability
- No dose optimisation and no concomitant immunomodulator, which is not how adalimumab is often used.
- Biologic-naive patients only.
- Not powered for endoscopic endpoints.
- Industry funded (Janssen Scientific Affairs).
Where it sits now
In biologic-naive moderate-to-severe Crohn's disease, ustekinumab was not superior to adalimumab monotherapy at 1 year and both worked well, so choose by patient factors, safety and preference.
- SEQUENCE (2024): After anti-TNF failure, risankizumab beats ustekinumab for endoscopic remission, so an IL-23 p19 inhibitor is the stronger second-line choice of the two.
Questions for discussion
- SEAVUE was designed to show superiority. Can you conclude that the two drugs are equivalent from a non-significant difference?
- Adalimumab could not be escalated and no immunomodulator was allowed. Which drug did those rules disadvantage more?
- How would you choose between ustekinumab and adalimumab for a biologic-naive patient with psoriasis, or with a strong preference about injection frequency?