Stelara vs Skyrizi for Crohn’s Disease: What the SEQUENCE Trial Means for Biologic Choice

Why this study matters

Choosing the right biologic treatment in Crohn’s disease is one of the most important decisions we make in clinic.

Most biologics are tested against placebo. True head to head studies between advanced therapies are rare, which is why the SEQUENCE trial attracted significant international attention.

For patients who have already failed anti TNF therapy such as infliximab or adalimumab, the next treatment choice can significantly affect long term disease control, steroid exposure, hospitalization risk and surgical risk.

What was studied?

The SEQUENCE trial directly compared two advanced biologic treatments for Crohn’s disease:

• Stelara also known as ustekinumab
• Skyrizi also known as risankizumab

The study followed Crohn’s disease patients over 48 weeks. These were patients who had already failed previous anti TNF therapy.

The trial looked not only at symptom improvement, but also at deeper inflammatory outcomes, including endoscopic remission.

Why endoscopic remission matters in Crohn’s disease

One of the biggest shifts in modern Crohn’s disease management is the move away from treating symptoms alone.

A patient may feel better while inflammation silently continues underneath.

Endoscopic remission means visible healing of the bowel lining during colonoscopy. This is increasingly considered one of the most important long term treatment targets in Crohn’s disease.

Endoscopic healing is important because it is associated with:

• Fewer Crohn’s disease flares
• Reduced steroid exposure
• Lower hospitalization risk
• Lower surgical risk
• Better long term disease control

What were the SEQUENCE trial results?

Both treatments were effective. However, Skyrizi showed higher rates of deep bowel healing in this study.

This difference in bowel healing rates is one of the most important findings from the trial.

For patients starting a new biologic after anti TNF failure, this result may influence how we think about biologic sequencing in Crohn’s disease.

Why might Skyrizi perform differently?

The way I think about this in clinic is through pathway precision.

Stelara blocks both IL 12 and IL 23 through the p40 pathway.

Skyrizi selectively blocks IL 23 through the p19 pathway.

Increasingly, research in Crohn’s disease suggests IL 23 may play a particularly important role in maintaining chronic intestinal inflammation.

This may partly explain why more selective IL 23 targeting is generating strong long term data in Crohn’s disease.

How I use this information in clinic

The mistake I often see is assuming every patient should switch treatments because of a new study.

That is not how Crohn’s disease care works.

If a patient is already doing well on Stelara, that treatment response is valuable biological information. Their immune system has already demonstrated that this pathway works for them.

This study is most useful at the decision point when choosing a new biologic after anti TNF failure.

For newer starts, the SEQUENCE trial suggests Skyrizi may offer a higher probability of deep bowel healing from the outset.

The bigger picture: Crohn’s biologic sequencing

Crohn’s disease management is increasingly moving toward precision medicine.

The future is unlikely to be simply asking, which biologic is strongest?

The better question is, which inflammatory pathway is driving this individual patient’s disease?

That shift toward pathway selection, biomarker prediction and biologic sequencing is where modern IBD care is heading.

Frequently Asked Questions

Is Skyrizi stronger than Stelara in Crohn’s disease?

The SEQUENCE trial showed higher endoscopic remission rates with Skyrizi compared with Stelara in Crohn’s disease patients who had previously failed anti TNF therapy.

Should I switch from Stelara to Skyrizi?

Not necessarily. If you are already stable and healing on Stelara, that response is important biological information. Treatment decisions should be individualized.

What is endoscopic remission?

Endoscopic remission means healing of the bowel lining seen during colonoscopy. It is an important treatment target in Crohn’s disease.

Why are head to head biologic trials important?

Head to head trials directly compare two active treatments. They are useful because many biologic trials compare a drug with placebo rather than another biologic.