Entyvio vs Stelara for Crohn's Disease: How They Compare

If your gastroenterologist has put Entyvio vs Stelara on the table, the honest starting point is that no head-to-head randomized trial has ever compared them in Crohn's disease (4). Everything we know comes from separate trials, indirect comparisons and matched cohorts. That sounds like bad news, but it makes the decision clearer: once you accept there is no single winner, the question becomes which of the two fits your treatment history, your other symptoms and your life.

Key Takeaways

• No head-to-head randomized trial comparing vedolizumab (Entyvio) and ustekinumab (Stelara) in Crohn's has ever been run, so every comparison is indirect (4)
• In 10 propensity score matched cohort studies covering 4,398 patients, steroid-free remission did not differ significantly at 12, 24 or 52 weeks (2)
• In anti-TNF-refractory patients across 16 studies and 6,584 people, ustekinumab was favoured for remission at 14 to 16 weeks (OR 1.41, 95% CI 1.01 to 1.98) (4)
• The December 2025 AGA living guideline rates both in the higher efficacy tier for advanced-therapy-naive patients, but drops vedolizumab to the lower tier and ustekinumab to the intermediate tier once you have failed one (1)
• The gut-selective drug did not win on safety: in matched cohorts ustekinumab had fewer serious infections (OR 0.61, 95% CI 0.47 to 0.80, p less than 0.001) (2)
• Neither drug carries an FDA boxed warning, which sets both apart from JAK inhibitors and anti-TNF agents (5, 6)

Entyvio vs Stelara: The Short Answer

There is no randomized head-to-head trial of Entyvio vs Stelara in Crohn's, so no one can tell you which is objectively better (4). Both are approved for moderately to severely active Crohn's, and neither carries an FDA boxed warning (5, 6). The headline difference is where they act: Entyvio works only in the gut, Stelara on a signalling pathway throughout the body. That one difference drives most of the trade-offs below.

The detail most comparisons leave out is treatment history. In the current AGA living guideline both sit in the top efficacy tier if you have never had an advanced therapy, but they separate once you have failed one (1). So when someone asks us which is better, the accurate answer is a question back: better for whom, and at what point?

How Each Drug Actually Works

Both drugs calm Crohn's inflammation, but at completely different points. Entyvio stops inflammatory immune cells entering the gut wall in the first place. Stelara switches off an inflammatory signal those cells respond to, wherever in the body it is sent. One is a doorman, the other a dimmer switch.

Entyvio: blocking the door into the gut

Vedolizumab binds the alpha-4-beta-7 integrin on certain white blood cells and blocks its interaction with MAdCAM-1, a molecule on blood vessels in the gut. Integrins are the docking clips a cell uses to cross out of the bloodstream, and MAdCAM-1 is the gut's docking port. Blocking that handshake stops inflammatory T-lymphocytes migrating into inflamed gastrointestinal tissue (5).

This is what gut-selective means: Entyvio acts at the gut lining rather than damping immunity body-wide. Many of us assume that must be safer, and we come back to whether the data supports it. Our guide to vedolizumab (Entyvio) covers the drug alone.

Stelara: switching off an inflammatory signal

Ustekinumab is a human IgG1-kappa monoclonal antibody, a lab-made antibody built to recognise one target: the p40 protein subunit shared by two inflammatory messengers, interleukin-12 and interleukin-23. By binding p40, Stelara disrupts that signalling pathway (6). Our Stelara (ustekinumab) patient guide goes deeper.

Because the IL-12 and IL-23 pathway is active throughout the body, Stelara is not gut-selective. That cuts both ways. It is a broader intervention, but it also means Stelara is approved for psoriasis and psoriatic arthritis, so for some people it treats skin and joint disease alongside the gut. Entyvio will not. If you live with extraintestinal manifestations, that is often the most practical difference.

Dosing, Infusions and Injections: What the Routine Looks Like

The schedules differ in ways that matter as much as efficacy. Stelara is one infusion then a self-injection every 8 weeks, roughly six injections a year. Entyvio is either an infusion every 8 weeks indefinitely or, after the first two infusions, a self-injection every 2 weeks, about 26 injections a year.

Entyvio schedule

Entyvio for Crohn's is 300 mg by intravenous infusion over roughly 30 minutes at week 0, week 2 and week 6, then every 8 weeks. After the first two IV doses, treatment can be switched at week 6 to 108 mg subcutaneously every 2 weeks, using either a prefilled syringe or the Entyvio Pen (5).

The label also sets a clear decision point: it directs discontinuation in patients with no evidence of therapeutic benefit by week 14 (5). Knowing that date in advance is useful, because it tells you when to expect a real conversation rather than an open-ended wait.

Stelara schedule

Stelara for adult Crohn's starts with a single weight-based IV induction dose: 260 mg at 55 kg or less, 390 mg above 55 kg up to 85 kg, and 520 mg above 85 kg. Eight weeks later you move to 90 mg subcutaneously, then 90 mg every 8 weeks (6).

So the infusion burden is front-loaded and then over. For people who work shifts or live far from an infusion centre, that can outweigh a lot of statistics. For people who find self-injection hard, an 8-weekly chair where a nurse does the work is relief, not burden.

What the Evidence Says When You Compare Them Indirectly

With no head-to-head trial, researchers use two workarounds: matching real-world patients so the groups look statistically similar, and network meta-analysis, which links separate trials through shared comparators. Both point the same way: the drugs look broadly comparable in unselected patients, and ustekinumab tends to edge ahead after anti-TNF failure.

Matched real-world cohorts

A 2024 meta-analysis of 10 propensity score matched cohort studies covering 4,398 patients found no statistically significant difference in steroid-free remission at any time point: 12 weeks (OR 1.31, 95% CI 0.88 to 1.94, p = 0.180), 24 weeks (OR 1.18, 95% CI 0.79 to 1.75, p = 0.420) and 52 weeks (OR 1.35, 95% CI 0.91 to 2.01, p = 0.140) (2).

Those odds ratios all sit above 1, which leans numerically towards ustekinumab, but the confidence intervals cross 1 and the p values are not significant. The analysis could not demonstrate a difference, which is not the same as proving they are identical.

After anti-TNF failure

The picture shifts once you have failed a TNF blocker. A 2025 meta-analysis of 16 studies and 6,584 anti-TNF-refractory patients favoured ustekinumab for clinical remission at 14 to 16 weeks (OR 1.41, 95% CI 1.01 to 1.98) and for steroid-free maintenance remission (OR 1.56, 95% CI 1.16 to 2.08). By 52 weeks there was no significant difference (OR 1.24, 95% CI 0.85 to 1.81) (4).

A 2025 Bayesian network meta-analysis of 31 randomized trials pointed the same way. Among six biologics, ustekinumab ranked highest for inducing clinical response in TNF-experienced patients (SUCRA 86.19), while vedolizumab did not show superiority in that group (3). SUCRA is a ranking statistic: the closer to 100, the more often that drug came out on top across the modelled comparisons.

The limits matter, because these numbers get quoted with more confidence than they deserve. Propensity matching and indirect comparison cannot replace a randomized head-to-head trial, and cohorts differ in how sick the patients were and why each drug was chosen (2, 4).

Safety: Where the Two Really Differ

Neither Entyvio nor Stelara carries an FDA boxed warning, a meaningful distinction from JAK inhibitors and anti-TNF agents (5, 6). Both labels still require infection screening before you start and ask your team to watch for specific neurological signs. The differences are in the detail.

The Entyvio label advises against starting during a clinically important active infection and directs tuberculosis screening beforehand. It states that a risk of progressive multifocal leukoencephalopathy, a rare brain infection, cannot be ruled out, and directs monitoring for new or worsening neurological signs (5). The most common adverse reactions in IV-treated patients were nasopharyngitis 13 percent, headache 12 percent, arthralgia 12 percent, nausea 9 percent and pyrexia 9 percent (5).

The Stelara label warns about serious bacterial, mycobacterial, fungal and viral infections, requires tuberculosis evaluation before treatment, flags a possible increased malignancy risk with monitoring for non-melanoma skin cancer, and notes reported cases of posterior reversible encephalopathy syndrome (6). We cover the long-term data in our article on whether Stelara is safe long term.

The counterintuitive part: in the matched-cohort meta-analysis, ustekinumab was associated with fewer adverse events (OR 0.54, 95% CI 0.35 to 0.83, p = 0.005), fewer serious infections (OR 0.61, 95% CI 0.47 to 0.80, p less than 0.001) and lower one-year hospitalization (OR 0.68, 95% CI 0.58 to 0.80, p less than 0.0001), even though Entyvio is the gut-selective drug (2). These are observational comparisons, not a trial, but the signal is strong enough that assuming Entyvio is the gentler choice is not supported.

Who Tends to Get Which, and What Guidelines Say

The AGA living clinical practice guideline published in Gastroenterology in December 2025 sorts Crohn's drugs into efficacy tiers, and treats these two differently depending on what you have already tried. For patients naive to advanced therapy, both vedolizumab and ustekinumab sit in the higher efficacy tier, alongside infliximab, adalimumab, risankizumab, mirikizumab and guselkumab (1).

For patients previously exposed to one or more advanced therapies, the same guideline moves ustekinumab to the intermediate efficacy tier and vedolizumab to the lower tier (1). That is the most decision-relevant fact here, and the piece most side-by-side articles skip. On certainty of evidence, the guideline rates ustekinumab high for induction and moderate for maintenance, and vedolizumab moderate for both (1). Risankizumab outranks ustekinumab for previously exposed patients in that framework, which is why our Skyrizi vs Stelara comparison is often the more relevant read if you have already failed a biologic.

In practice the choice turns on four things: where you are in your treatment history, how much extraintestinal disease you have, how you feel about infusions versus injections, and what your insurer or health system will cover. That last point varies enormously by country, and in some systems the formulary decides before your gastroenterologist.

Questions to bring to your gastroenterologist

• Have I already failed an advanced therapy, and does that change which of these you would pick for me?
• Do I have joint, skin or eye involvement that one of these might also help?
• If I start Entyvio, will I stay on infusions or move to the every-2-week subcutaneous pen?
• What is the plan if there is no response by week 14 on Entyvio, or by the second maintenance dose of Stelara?
• Given my insurance or health system, which of these can I start soonest?

Entyvio vs Stelara is not a contest with a winner. It is a matching exercise, and the strongest input is your own history. If you have never had an advanced therapy, the guidelines treat both as top-tier and the practical factors take the lead. If you have failed one, the evidence and the tiers lean towards ustekinumab. Either way, the decision belongs with your IBD team.

Frequently Asked Questions

Is Entyvio or Stelara better for Crohn's disease?

No head-to-head randomized trial has ever compared them, so neither can be called better overall (4). In matched real-world cohorts, steroid-free remission rates did not differ significantly at 12, 24 or 52 weeks (2). In patients who have already failed an anti-TNF, indirect evidence leans towards ustekinumab for earlier remission (4).

Is Entyvio safer than Stelara because it only works in the gut?

Gut-selectivity does not automatically mean better safety outcomes. In the matched-cohort meta-analysis, ustekinumab was associated with fewer adverse events (OR 0.54, p = 0.005), fewer serious infections (OR 0.61, p less than 0.001) and lower one-year hospitalization (OR 0.68, p less than 0.0001) (2). Neither drug carries an FDA boxed warning (5, 6).

Can I switch from Entyvio to Stelara?

Switching biologics is routine when a drug is not controlling the disease, and because these two act on completely different targets, one can work after the other has failed. The Entyvio label directs discontinuation if there is no therapeutic benefit by week 14, often the natural point for that conversation (5).

Which one helps joint or skin symptoms too?

Stelara works on the IL-12 and IL-23 pathway body-wide and is also approved for psoriasis and psoriatic arthritis, so it may cover some extraintestinal manifestations (6). Entyvio acts at the gut lining and is not expected to help skin or joint disease (5). Raise this specifically with your team.

Does insurance cover Entyvio and Stelara for Crohn's?

Coverage varies widely by country and plan, and in many systems the formulary, not the clinician, decides which biologic you can start first. Both are widely funded for moderately to severely active Crohn's where approval criteria are met, and ustekinumab biosimilars have begun to change the cost picture in several markets. Ask your clinic's specialist nurse what your route looks like.

References

1. Ananthakrishnan AN, et al. AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn's Disease. Gastroenterology, 2025. Read guideline
2. Ahmed Z, et al. Comparison of the Safety and Efficacy of Ustekinumab and Vedolizumab in Patients with Crohn's Disease: A Systematic Review and Meta-Analysis of Propensity Score Matched Cohort Studies. 2024. Read study
3. Systematic review and Bayesian network meta-analysis: comparative efficacy and safety of six commonly used biologic therapies for moderate-to-severe Crohn's disease. 2025. Read study
4. Ustekinumab versus vedolizumab in patients with Crohn's disease refractory to anti-tumour necrosis factor: A systematic review and meta-analysis. 2025. Read study
5. Takeda Pharmaceuticals. ENTYVIO (vedolizumab) and ENTYVIO PEN prescribing information. DailyMed, 2025. Read label
6. Janssen Biotech. STELARA (ustekinumab) injection, solution prescribing information. DailyMed, 2025. Read label