Stelara (Ustekinumab) for Crohn's Disease: A Patient Guide

Quick answer: Stelara (ustekinumab) is a biologic medicine approved for moderately to severely active Crohn's disease. It works by blocking two inflammatory proteins, interleukin-12 (IL-12) and interleukin-23 (IL-23), that drive gut inflammation. Treatment starts with a single weight-based intravenous (IV) infusion, followed by a 90 mg injection under the skin every 8 weeks. In the pivotal UNITI trials, ustekinumab produced significantly higher response and remission rates than placebo, with a generally favorable safety profile [1].

Key Takeaways

• Stelara (ustekinumab) targets the shared p40 subunit of IL-12 and IL-23, two signaling proteins involved in Crohn's inflammation [1].
• In the UNITI-1 induction trial (patients who had failed anti-TNF drugs), about 34% responded at week 6 on ustekinumab versus 21.5% on placebo. In UNITI-2 (conventional-therapy failures), 55.5% of the weight-based dose group responded versus 28.7% on placebo [1].
• In the IM-UNITI maintenance trial, 53.1% of patients on 90 mg every 8 weeks were in remission at week 44, compared with 35.9% on placebo [1].
• Standard dosing is one weight-based IV induction dose, then 90 mg subcutaneous (under the skin) every 8 weeks [2].
• A 5-year extension reported no new safety signals, and serious infection rates were low [3].
• Several FDA-approved ustekinumab biosimilars are now available, which may lower cost [4].

How Stelara Works

Crohn's disease is driven in part by an overactive immune response in the lining of the gut. Two messenger proteins called interleukin-12 (IL-12) and interleukin-23 (IL-23) help switch on and sustain this inflammation. Both proteins share a common building block known as the p40 subunit.

Stelara (ustekinumab) is a monoclonal antibody that binds to that shared p40 subunit. By attaching to p40, it blocks both IL-12 and IL-23 from connecting to immune cells, which dials down the inflammatory signaling that fuels Crohn's flares [1]. This is a different mechanism from anti-TNF biologics like infliximab and adalimumab, which is one reason ustekinumab can work for people who did not respond to those drugs.

If you are weighing this medicine against a newer, more selective IL-23 blocker, our comparison of Skyrizi versus Stelara for Crohn's walks through the differences.

What the Trials Showed

Ustekinumab's approval in Crohn's disease was built on a coordinated program of three Phase 3 trials, published together in the New England Journal of Medicine in 2016 [1]. Two trials tested induction (getting the disease under control) and one tested maintenance (keeping it under control).

UNITI-1 (anti-TNF failures)

UNITI-1 enrolled 741 patients who had not responded to, or could not tolerate, TNF-antagonist therapy. This is a harder-to-treat group. The primary endpoint was clinical response at week 6. Response rates were 34.3% (130 mg IV) and 33.7% (weight-based dose, about 6 mg/kg) versus 21.5% for placebo, with P less than or equal to 0.003 for both comparisons [1].

UNITI-2 (conventional-therapy failures)

UNITI-2 enrolled 628 patients in whom conventional therapy (such as steroids or immunomodulators) had failed. Response rates at week 6 were 51.7% (130 mg IV) and 55.5% (weight-based dose) versus 28.7% for placebo, with P less than 0.001 for both doses [1].

IM-UNITI (maintenance)

Patients who responded to induction were re-randomized in the IM-UNITI maintenance trial. The primary endpoint was remission (a Crohn's Disease Activity Index score below 150) at week 44. Remission rates were 53.1% for 90 mg every 8 weeks and 48.8% for 90 mg every 12 weeks, compared with 35.9% for placebo (P=0.005 and P=0.04, respectively) [1].

A long-term extension followed patients out to 5 years (week 252). Using a conservative intent-to-treat analysis of all randomized patients, 34.4% of the every-8-weeks group and 28.7% of the every-12-weeks group were still in remission at 5 years. The authors reported no new safety signals over the extension period [3].

What Is the Dosing Schedule for Stelara in Crohn's Disease?

Stelara for Crohn's begins with a single IV infusion dosed by body weight, followed by maintenance injections you can eventually give yourself at home. The first subcutaneous (under the skin) dose is given 8 weeks after the IV infusion, then continued every 8 weeks [2].

| Phase | Route | Dose | Timing | | --- | --- | --- | --- | | Induction (weight 55 kg or less) | IV infusion | 260 mg | Single dose | | Induction (weight over 55 kg up to 85 kg) | IV infusion | 390 mg | Single dose | | Induction (weight over 85 kg) | IV infusion | 520 mg | Single dose | | Maintenance | Subcutaneous injection | 90 mg | Every 8 weeks |

Source: FDA prescribing information for Stelara [2]. Always follow the exact schedule your own gastroenterology team gives you.

Who Is Stelara For?

Stelara is approved for adults with moderately to severely active Crohn's disease [2]. In practice, gastroenterologists often consider it for:

• People who have not responded well to, or could not tolerate, anti-TNF biologics. UNITI-1 was designed specifically around this group [1].
• People who failed conventional therapies such as corticosteroids or immunomodulators, as studied in UNITI-2 [1].
• People who prefer a less frequent maintenance schedule (every 8 weeks) and a favorable safety record.

Your doctor will review your medical history, prior treatments, infection risk, and screening tests before starting any biologic.

Is Stelara Safe? What Are the Side Effects?

Across the UNITI program and its long-term follow-up, ustekinumab had a generally favorable safety profile. In the 5-year IM-UNITI extension, the authors reported no new safety signals, and serious infection rates remained low [3].

Because Stelara suppresses parts of the immune system, the most important consideration is infection risk. Before starting, your team will typically screen for tuberculosis and check for other infections. The FDA label advises caution in people with active infections and notes the importance of completing appropriate vaccinations beforehand [2]. Other reported side effects include reactions at the injection site, headache, and nasopharyngitis (cold-like symptoms). Tell your doctor promptly about any fever, persistent cough, or signs of infection.

This article is general education. Your individual risks depend on your health history, so discuss them directly with your prescriber.

Are There Stelara Biosimilars?

Yes. Several FDA-approved ustekinumab biosimilars are now on the market in the United States. The first, Wezlana (ustekinumab-auub), was approved with an interchangeability designation, and it has since been joined by others including Selarsdi, Pyzchiva, Otulfi, Imuldosa, Yesintek, and Steqeyma [4].

Biosimilars are highly similar to the original biologic, with no clinically meaningful differences in safety or effectiveness, and they are typically less expensive. For a fuller explanation of how these work and what to expect, see our patient guide to biosimilars for Crohn's disease.

What Should I Expect When Starting Treatment?

The first dose is an IV infusion given at a clinic or infusion center, which usually takes about an hour. After that, maintenance is a single injection under the skin every 8 weeks, which many patients learn to do at home with a prefilled syringe or pen [2].

Some people notice improvement within the first few weeks, while for others it builds more gradually. Keep all follow-up appointments so your team can track how you are responding, adjust if needed, and monitor for side effects. If you do not respond to induction, your doctor may consider an additional dose or a different therapy.

Frequently Asked Questions

How is Stelara given for Crohn's disease?

The first dose is a single weight-based IV infusion. After that, maintenance is a 90 mg injection under the skin, starting 8 weeks after the infusion and then every 8 weeks [2].

How well does Stelara work?

In the UNITI-2 trial, 55.5% of patients on the weight-based induction dose responded by week 6 versus 28.7% on placebo. In maintenance, 53.1% of patients on the every-8-weeks dose were in remission at week 44 versus 35.9% on placebo [1].

Can Stelara be used after anti-TNF biologics stop working?

Yes. The UNITI-1 trial enrolled only patients who had failed or could not tolerate anti-TNF drugs, and ustekinumab still outperformed placebo at week 6 [1].

Is Stelara safe long term?

A 5-year extension of IM-UNITI reported no new safety signals, with low rates of serious infection [3]. Because it affects the immune system, infection screening and monitoring are important [2].

Are there cheaper versions of Stelara?

Yes. Multiple FDA-approved ustekinumab biosimilars are now available and are generally less costly than the original [4].

Can I give Stelara to myself at home?

The maintenance injections are designed for self-administration under the skin, and many patients do them at home after training. The initial IV dose is given in a medical setting [2].

How is Stelara different from Skyrizi?

Stelara blocks both IL-12 and IL-23, while Skyrizi (risankizumab) selectively blocks IL-23. See our Skyrizi versus Stelara comparison for details.

This article is for general educational purposes only and is not medical advice. It does not replace a conversation with your own gastroenterologist or healthcare provider. Always discuss treatment decisions, dosing, and side effects with a qualified clinician before making any changes.

References

1. Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. New England Journal of Medicine. 2016;375(20):1946-1960. https://www.nejm.org/doi/10.1056/NEJMoa1602773
2. U.S. Food and Drug Administration. STELARA (ustekinumab) Highlights of Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761044s010lbl.pdf
3. Sandborn WJ, Rebuck R, Wang Y, et al. Five-Year Efficacy and Safety of Ustekinumab Treatment in Crohn's Disease: The IM-UNITI Trial. Clinical Gastroenterology and Hepatology. 2022;20(3):578-590.e4. https://pmc.ncbi.nlm.nih.gov/articles/PMC8374005/
4. U.S. Food and Drug Administration. Biosimilar Product Information. https://www.fda.gov/drugs/biosimilars/biosimilar-product-information