Entyvio vs Skyrizi for Crohn's Disease: A Patient Comparison

If your gastroenterologist has put Entyvio vs Skyrizi in front of you, the honest starting point is that no head-to-head randomised trial has ever compared them in Crohn's disease. Every set of percentages stacked side by side online comes from separate trials, run in different decades, in different patients, against different endpoints. Many of us have had to make this choice anyway, so this comparison skips the false scoreboard and looks at where the two drugs really separate.

Key Takeaways

• Entyvio (vedolizumab) blocks alpha-4-beta-7 integrin in the gut lining; Skyrizi (risankizumab) blocks the IL-23 p19 subunit body-wide (7, 8)
• No head-to-head randomised trial of Entyvio vs Skyrizi exists in Crohn's, so every comparison between them is modelled rather than measured
• In ADVANCE, week 12 remission was 45 percent on risankizumab 600 mg versus 25 percent on placebo, endoscopic response 40 versus 12 percent (3)
• In GEMINI 2, week 52 remission was 39.0 percent among every-8-week vedolizumab responders versus 21.6 percent on placebo (5)
• The 2025 AGA guideline rates both higher efficacy for advanced-therapy-naive patients, but drops vedolizumab to lower efficacy once one has failed (1)
• Neither carries a boxed warning, and the calendars differ: about 6 injections a year on Skyrizi maintenance versus 6 to 7 infusions or 26 home injections on Entyvio (7, 8)

Entyvio and Skyrizi: Two Very Different Approaches

Entyvio and Skyrizi both calm Crohn's inflammation, but at completely different points. Entyvio works at the door of the gut, stopping inflammatory immune cells from entering the intestinal lining. Skyrizi works upstream, switching off one of the signals that recruits that inflammation in the first place. Neither target is automatically the better one.

How Entyvio (vedolizumab) works

Entyvio is an integrin receptor antagonist. It blocks alpha-4-beta-7 integrin, the docking signal inflammatory white blood cells use to cross out of the bloodstream and into the gut lining (7). Because that signal is largely gut-specific, Entyvio is described as gut-selective: it does comparatively little elsewhere in the body. Our full Entyvio patient guide covers the mechanism in more depth.

How Skyrizi (risankizumab) works

Skyrizi is an interleukin-23 antagonist. It binds the p19 subunit of IL-23, a signalling protein that drives the inflammatory cascade in Crohn's (8). IL-23 acts throughout the body, not only in the gut, which is why risankizumab is also approved for plaque psoriasis and psoriatic arthritis. Our overview of IL-23 inhibitors for Crohn's disease shows where it sits alongside mirikizumab and guselkumab.

The pattern runs fairly consistently through the evidence: a gut-selective target tends to mean a quieter systemic safety profile, a systemic pathway target a stronger effect on intestinal inflammation. That is a trade-off, not a ranking.

What the Trials Actually Showed

Both drugs beat placebo in the trials that won them approval. Skyrizi's programme is recent, large and reported endoscopic healing as a co-primary endpoint. Entyvio's pivotal Crohn's trial is from 2013 and used a week 6 endpoint we now understand was too early for this drug.

Skyrizi: ADVANCE, MOTIVATE and FORTIFY

In ADVANCE, CDAI clinical remission at week 12 was 45 percent on risankizumab 600 mg versus 25 percent on placebo. In MOTIVATE, which enrolled patients who had already failed biologic therapy, it was 42 percent versus 20 percent. Endoscopic response was 40 percent versus 12 percent in ADVANCE and 29 percent versus 11 percent in MOTIVATE (3).

FORTIFY, the maintenance trial, used a withdrawal design. At week 52 on 360 mg, CDAI remission was 52 percent versus 41 percent among those withdrawn to placebo, and endoscopic response 47 percent versus 22 percent (4). That endoscopic gap is the figure gastroenterologists focus on, because visible mucosal healing is harder to achieve than symptom relief.

Entyvio: GEMINI 2

GEMINI 2 reported clinical remission at week 6 of 14.5 percent on vedolizumab versus 6.8 percent on placebo, and the CDAI-100 response endpoint was not met. At week 52, 39.0 percent of responders continuing every-8-week dosing were in remission, versus 21.6 percent on placebo (5).

The week 6 result looks weak, and alone it is. But Entyvio is now understood to work slowly, and the current label says to consider discontinuation if there is no therapeutic benefit by week 14, not week 6 (7). In hindsight, that trial measured the wrong moment.

Why you cannot just compare the percentages

The trials above enrolled different populations, in different eras of IBD care, with different endpoints and different proportions of biologic-exposed patients. A 45 percent from 2022 and a 14.5 percent from 2013 are not readings off the same ruler.

Entyvio vs Skyrizi: What Indirect Comparisons Suggest

With no head-to-head trial, researchers use network meta-analysis, which connects drugs through their shared comparison with placebo. Two recent analyses agree on something decision-relevant: in biologic-naive patients these drugs look comparable, and once a biologic has failed they separate.

Biologic-naive patients

The 2025 AGA evidence synthesis placed both vedolizumab and risankizumab among the options supported by moderate-to-high certainty evidence for inducing remission in biologic-naive patients (2). If this is your first advanced therapy, the evidence does not pick a winner for you.

Patients who have already tried a biologic

Here the picture changes. In patients with prior biologic exposure, the 2025 AGA synthesis found moderate certainty evidence supporting risankizumab and guselkumab over vedolizumab and ustekinumab for inducing remission, and rated the evidence for vedolizumab in that group only low certainty (2).

The 2026 Cochrane network meta-analysis adds nuance. For induction it rated vedolizumab moderate certainty with a trivial effect size (RR 1.57, NNTB 10), and risankizumab low certainty with a moderate effect size (RR 2.26) (6). Read plainly: Entyvio has the smaller but more certain effect, Skyrizi the larger but less certain one. Cochrane also found low certainty evidence that risankizumab may lead to fewer withdrawals due to adverse events (RR 0.36) (6).

Skyrizi has been compared head-to-head with Stelara in the SEQUENCE trial, so our Skyrizi vs Stelara comparison covers that evidence. One caveat holds throughout: indirect comparisons are modelled, not measured.

Safety: What to Watch For With Each

Neither Entyvio nor Skyrizi carries a boxed warning, a meaningful difference from JAK inhibitors such as upadacitinib (Rinvoq) (7, 8). Both sit at the safer end of the advanced therapy spectrum, but what each label asks doctors to watch for differs.

Entyvio safety

The Entyvio label lists infusion-related and hypersensitivity reactions including anaphylaxis, infections, and progressive multifocal leukoencephalopathy (PML) under warnings and precautions. On PML it says a risk cannot be ruled out, notes one postmarketing case in a patient with multiple contributory factors, and asks clinicians to monitor for new or worsening neurological symptoms (7). That is not a statement that Entyvio causes PML, but it is why such symptoms are worth reporting rather than waiting out.

Skyrizi safety

The Skyrizi label lists hypersensitivity reactions including anaphylaxis, infections, tuberculosis evaluation before starting, and hepatotoxicity, and notes that drug-induced liver injury during IBD induction has been reported (8). So the label instructs clinicians to obtain liver enzymes and bilirubin before starting and to keep monitoring during induction for at least 12 weeks (8). If your gastroenterologist orders repeat blood tests through your infusion phase, this is why.

What both share

Both labels ask for tuberculosis consideration or evaluation before starting, and for immunisations to be up to date beforehand (7, 8). In our community, the people who find this easiest sorted their vaccinations before the first dose rather than during it.

Dosing Burden: Infusion Chairs, Pens and Calendars

Trial percentages get the attention, but the dosing calendar is the part you live with, and these two ask different things of your year.

What a year on Entyvio looks like

Entyvio by infusion is 300 mg over roughly 30 minutes at weeks 0, 2 and 6, then every 8 weeks, settling into about 6 to 7 infusion visits a year (7). There is also a subcutaneous route: after the first two intravenous doses at weeks 0 and 2, you can switch to 108 mg by prefilled syringe or the Entyvio Pen every 2 weeks at home. That is roughly 26 injections a year, but no infusion centre (7).

What a year on Skyrizi looks like

Skyrizi front-loads the clinic time: 600 mg intravenously over at least one hour at weeks 0, 4 and 8. Maintenance is then 180 mg or 360 mg subcutaneously at week 12 and every 8 weeks after, about 6 injections a year (8).

So the honest comparison is this: Skyrizi front-loads the clinic time and then becomes the lighter long-term schedule, while Entyvio is either a steady every-8-week infusion rhythm or an every-2-week injection rhythm at home. If you are needle-averse, far from an infusion centre, or travelling for work, that is a real decision input, not a footnote.

Where Guidelines Put Each Drug, and When Doctors Reach for Each

Guidelines will not choose for you, but they show how the evidence is currently read. On these two drugs they say something specific and often skipped: the answer depends on whether you have already been through an advanced therapy.

What the 2025 AGA living guideline says

The AGA's 2025 living clinical practice guideline on moderate-to-severe Crohn's disease is the current reference, and it replaced the 2021 version. That matters here, because the 2021 guideline predated Skyrizi's Crohn's approval and could not include it.

For patients naive to advanced therapies, the 2025 guideline groups infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab and guselkumab together as higher efficacy options, and suggests using one of them rather than a lower efficacy medication (1). For patients already exposed to one or more advanced therapies, it lists adalimumab, risankizumab, guselkumab and upadacitinib as higher efficacy, and places vedolizumab in the lower efficacy group alongside certolizumab pegol (1). The guideline also suggests starting an advanced therapy up front rather than stepping through corticosteroids and immunomodulators first (1).

Read in one line: first-line, the guideline treats these two as peers; after a biologic has failed, it leans toward Skyrizi over Entyvio.

When a gastroenterologist may favour Entyvio

Your doctor may lean toward Entyvio if you are biologic-naive, if a history of recurrent or serious infection gives you reason to want a gut-selective drug, if you have no skin or joint disease needing treatment, or if you both value its long safety record highly.

When a gastroenterologist may favour Skyrizi

They may lean toward Skyrizi if an anti-TNF has already failed, if endoscopic healing is an explicit goal, if you also live with plaque psoriasis or psoriatic arthritis, or if you want the lighter maintenance schedule once induction is behind you.

Sometimes it comes down to none of that. Insurance step-therapy rules, infusion centre access, copay assistance and formulary placement shape what you can actually start, and they vary enormously by country. In some systems the plan decides before your gastroenterologist does.

Questions to bring to your appointment

• Am I biologic-naive or biologic-exposed in your eyes, and does that change which of these you would pick?
• Which endpoint matters most for my disease right now: symptoms, endoscopic healing, or staying off steroids?
• How will we know by week 14 or week 24 whether this is working?
• What is the plan if it is not?
• Given my insurance or health system, which of these can I start soonest?

Entyvio vs Skyrizi is not a contest with a winner. It is a matching exercise, and your treatment history is the strongest single input. For how both sit against the wider field, see our overview of the best biologic for Crohn's disease. This is a shared decision, and neither drug is the default answer.

Frequently Asked Questions

Is Entyvio or Skyrizi better for Crohn's disease?

No head-to-head randomised trial has compared them, so neither is better overall. For biologic-naive patients, the 2025 AGA evidence synthesis supported both with moderate-to-high certainty (2). Once a biologic has failed, moderate certainty evidence supported risankizumab over vedolizumab, and the vedolizumab evidence there was low certainty (2).

How long does each drug take to work?

Skyrizi's induction endpoint was week 12, with clinical remission in 45 percent of patients on 600 mg in ADVANCE (3). Entyvio works more slowly, and its label directs clinicians to consider discontinuation if there is no benefit by week 14 rather than judging earlier (7). Ask your team which week they will reassess you.

Is Skyrizi safe for the liver?

Drug-induced liver injury during IBD induction has been reported, so the label instructs clinicians to check liver enzymes and bilirubin before starting and to keep monitoring for at least 12 weeks of induction (8). That is standard monitoring, not a sign of trouble. Tell your team promptly about unusual fatigue, dark urine or yellowing of the skin or eyes.

Can I switch from Entyvio to Skyrizi?

Switching is routine when a drug is not controlling the disease, and because these two act on different targets, one can work after the other has not. The 2025 AGA guideline puts risankizumab in the higher efficacy group for advanced-therapy-exposed patients and vedolizumab in the lower group (1), which is part of why this direction is common.

Which one is easier to fit around normal life?

Skyrizi maintenance is about 6 subcutaneous doses a year after three initial infusions (8). Entyvio is either about 6 to 7 infusions a year or roughly 26 home injections after the first two intravenous doses (7). Which fits better depends on infusion centre access, your work pattern and how you feel about self-injecting.

Does either drug help joint or skin symptoms?

Skyrizi blocks IL-23 body-wide and is also approved for plaque psoriasis and psoriatic arthritis, so it may help some extraintestinal manifestations (8). Entyvio acts mainly at the gut lining and is not expected to help skin or joint disease (7). If you have significant joint or skin involvement, raise it, because it can shift the decision.

References

1. Ananthakrishnan AN, et al. AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn's Disease. Gastroenterology, 2025. View on PubMed
2. Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Crohn's Disease: 2025 AGA Evidence Synthesis. Gastroenterology, 2025. View on PubMed
3. D'Haens G, et al. Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials. The Lancet, 2022. View on PubMed
4. Ferrante M, et al. Risankizumab as maintenance therapy for Crohn's disease: the phase 3 FORTIFY withdrawal trial. The Lancet, 2022. View on PubMed
5. Sandborn WJ, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease (GEMINI 2). New England Journal of Medicine, 2013. View on PubMed
6. Biologic drugs for induction and maintenance of remission in Crohn's disease: a network meta-analysis. Cochrane Database of Systematic Reviews, 2026. View on PubMed
7. Takeda Pharmaceuticals. ENTYVIO (vedolizumab) prescribing information. DailyMed, revised 2/2026. Read label
8. AbbVie. SKYRIZI (risankizumab-rzaa) prescribing information. FDA, revised 6/2026. Read label