Anti-integrin Therapy

Anti-integrin therapies are biologic medicines that calm inflammatory bowel disease by blocking certain white blood cells from entering the gut lining. The main drug in this class is vedolizumab, a gut-selective biologic with a reassuring safety profile. It is used for moderate to severe Crohn’s disease and ulcerative colitis when standard treatments are not enough, and it can be given by infusion or injection. (entyviohcp.com)

Key Takeaways

• Anti-integrin therapy blocks α4β7 integrin, a “homing signal” that guides inflammatory immune cells into the gut, helping reduce bowel inflammation with limited effects on the rest of the body. (entyviohcp.com)

• Vedolizumab is currently the only gut-selective anti-integrin approved for adults with moderate to severe ulcerative colitis and Crohn’s disease in the United States. (entyvio.com)

• It is started as IV infusions at weeks 0, 2, and 6, then usually every 8 weeks, or switched to 108 mg injections every 2 weeks for maintenance after IV induction. (drugs.com)

• In large trials and real‑world studies, about 3–6 out of 10 patients achieve clinical remission by one year, with higher success rates in those who have never used another biologic. (pubmed.ncbi.nlm.nih.gov)

• Overall, vedolizumab has a favorable infection and cancer safety profile compared with older systemic biologics, although monitoring for infections and rare complications is still important. (pubmed.ncbi.nlm.nih.gov)

• Older anti‑integrin natalizumab works for Crohn’s but carries a clear risk of a rare brain infection (PML), so it is used rarely; newer gut‑selective integrin or MAdCAM‑1 blockers remain research drugs only. (fda.gov)

What is anti-integrin therapy?

Immune cells use “adhesion molecules” called integrins to leave the bloodstream and enter tissues.
The α4β7 integrin is a key homing signal that helps certain white blood cells find and enter the intestinal lining, where they can drive chronic inflammation in Crohn’s disease and ulcerative colitis. (entyviohcp.com)

Anti-integrin therapies are monoclonal antibodies that block these adhesion steps.
For IBD, the main target is α4β7:

• Vedolizumab binds directly to α4β7 and blocks its interaction with MAdCAM‑1, a molecule mainly found on blood vessels in the gut. (entyviohcp.com)

• This keeps many inflammatory lymphocytes from entering the intestinal wall, while leaving most of the rest of the immune system relatively intact. (pubmed.ncbi.nlm.nih.gov)

Natalizumab, an older anti‑integrin, blocks the broader α4 integrin family, which affects immune traffic into the brain as well as the gut.
That broader action explains its higher risk of progressive multifocal leukoencephalopathy (PML), a rare but often devastating brain infection. (pubmed.ncbi.nlm.nih.gov)

Vedolizumab: the main gut-selective option

Who is vedolizumab for?

In the United States, vedolizumab (brand name Entyvio) is approved for adults with:

• Moderately to severely active ulcerative colitis

• Moderately to severely active Crohn’s disease

who have:

• Not responded well to, lost response to, or not tolerated

• corticosteroids, or

• immunomodulators (thiopurines or methotrexate), or

• anti‑TNF biologics. (drugs.com)

Real‑world studies and expert guidelines support vedolizumab as a first biologic option for many patients, especially:

• Older or frail individuals

• People with a history of serious infections or certain cancers, where lower systemic immune suppression is a priority. (wjgnet.com)

At the same time, comparative studies in older adults suggest anti‑TNF agents may control Crohn’s disease more effectively than vedolizumab, with similar serious infection risks. (jamanetwork.com)
Treatment choice usually weighs speed and strength of response against safety concerns and individual risk factors.

How vedolizumab is given

Two formulations are available:

• Intravenous (IV) infusion

• 300 mg at weeks 0, 2, and 6

• then 300 mg every 8 weeks for maintenance

• Subcutaneous (under‑the‑skin) injection

• After at least 2 IV doses (typically weeks 0 and 2),

• 108 mg every 2 weeks starting at week 6, instead of the next IV infusion. (drugs.com)

If there is no clear benefit by about week 14, product labeling suggests reconsidering treatment. (drugs.com)

Many people stay on vedolizumab for years. Dose-interval shortening (for example, IV every 4 weeks) or switching IV to subcutaneous dosing is sometimes used if the initial response fades. (pubmed.ncbi.nlm.nih.gov)

How well does it work?

Across pivotal trials and real‑world cohorts:

• A meaningful symptom response often appears by week 6, and may deepen out to weeks 10–14, especially in Crohn’s disease. (wjgnet.com)

• In major phase 3 trials, about 3–4 out of 10 patients on vedolizumab were in clinical remission at 1 year, compared with fewer on placebo. (pubmed.ncbi.nlm.nih.gov)

• In people who had never received another biologic, remission rates at one year can be higher, around 6 in 10 in some real‑world series. (pubmed.ncbi.nlm.nih.gov)

Ulcerative colitis tends to respond faster and more reliably than Crohn’s disease, but many Crohn’s patients still achieve good long‑term control, especially when treatment is continued beyond the first few months. (pubmed.ncbi.nlm.nih.gov)

Safety and side effects

Common side effects

In studies and post‑marketing experience, the most frequently reported side effects include: (entyvio.com)

• Cold‑like symptoms (runny nose, sore throat, cough)

• Headache and fatigue

• Joint or back pain

• Nausea

• Mild fevers

• Rash or itching

• Infusion reactions (for IV) or injection‑site redness, itching, or soreness (for injections)

These are usually mild to moderate and often improve over time.

Infections

Because vedolizumab mainly targets immune cells going into the gut, it causes less widespread immune suppression than many older drugs.
Even so, serious infections can occur, including pneumonia, sepsis, and gut infections such as C. difficile. (entyviohcp.com)

Large database studies show:

• Overall rates of serious infection with vedolizumab are similar to anti‑TNF agents, and in ulcerative colitis may even be lower. (pubmed.ncbi.nlm.nih.gov)

• In Crohn’s disease, serious infection risk is comparable, but gut infections (for example, enteric infections) can be relatively more common, likely because the drug focuses immune effects in the intestine. (pubmed.ncbi.nlm.nih.gov)

Screening for tuberculosis and hepatitis B, updating vaccines, and monitoring for fevers or new symptoms remain standard practice.

Cancer risk

So far, long‑term extension studies and large observational cohorts have not shown higher overall cancer rates with vedolizumab compared with:

• Background IBD populations, or

• Patients on anti‑TNF therapy. (pubmed.ncbi.nlm.nih.gov)

This is reassuring but not definitive, since very long‑term data over many decades are still limited.

PML and comparison with natalizumab

Natalizumab, an older anti‑α4 integrin used mainly for multiple sclerosis and occasionally Crohn’s disease, clearly increases the risk of progressive multifocal leukoencephalopathy (PML).
Because of this, it carries a boxed warning and is available only through a restricted program. (fda.gov)

Vedolizumab was designed to avoid this problem by sparing α4β1 in the brain. To date:

• Long‑term trials and post‑marketing surveillance have not shown a PML signal similar to natalizumab. (pubmed.ncbi.nlm.nih.gov)

• The prescribing information reports one PML case in a vedolizumab‑treated patient with multiple other risk factors, and states the risk cannot be ruled out. (entyviohcp.com)

Clinicians remain alert for new neurologic symptoms, but overall PML risk with vedolizumab appears extremely low compared with natalizumab.

Pregnancy and breastfeeding

Pregnancy data for vedolizumab are expanding:

• A large prospective pregnancy registry and national database studies have not found increased rates of major birth defects, pregnancy loss, or serious infant infections compared with anti‑TNF‑exposed or disease‑matched controls. (pubmed.ncbi.nlm.nih.gov)

• Earlier small studies and one meta‑analysis suggested more preterm births, but these were likely confounded by high disease activity. (pubmed.ncbi.nlm.nih.gov)

• Drug levels in exposed infants usually fall to undetectable levels by about 3 months of age, after which routine live vaccines like rotavirus have been given safely. (pubmed.ncbi.nlm.nih.gov)

Current evidence is generally reassuring, but pregnancy decisions still weigh disease control against any potential risks on a case‑by‑case basis.

Extraintestinal manifestations

Because vedolizumab is gut‑selective, its effect on joints, skin, and eyes is mixed:

• Around 40% of pre‑existing joint or skin extraintestinal manifestations improve or resolve, especially when gut disease is controlled. (pubmed.ncbi.nlm.nih.gov)

• New or worsened extraintestinal problems, especially joint pain or certain skin lesions, can also appear on treatment, sometimes leading to drug discontinuation. (mayoclinic.elsevierpure.com)

When extraintestinal disease (for example axial spondyloarthritis or uveitis) is a major concern, more systemic biologics such as anti‑TNF or IL‑23‑pathway drugs are often favored.

Other gut-selective biologics in this pathway

Several other molecules have tried to copy or refine the gut‑selective idea:

• Natalizumab (Tysabri) is an anti‑α4 integrin that works in Crohn’s disease but is limited by its PML risk and is rarely used for IBD today. (cochrane.org)

• Etrolizumab, a β7‑targeting antibody, and ontamalimab (SHP647/TAK‑647), an anti‑MAdCAM‑1 antibody, showed promising gut‑selective activity and good short‑term safety, but large phase 3 programs produced mixed or disappointing results. Their IBD development programs were subsequently stopped, so they are not available outside clinical trials. (en.wikipedia.org)

For now, vedolizumab remains the main approved gut‑selective biologic for Crohn’s disease and ulcerative colitis.

When might anti-integrin therapy be considered?

Care teams often consider vedolizumab when:

• Disease is moderate to severe and needs an advanced therapy

• There is concern about serious infections, blood clots, or certain cancers, where a gut‑focused drug is appealing

• The main goal is durable control of colon‑dominant disease, especially in ulcerative colitis

• Other biologics have failed or caused side effects, and a different mechanism is desired. (pubmed.ncbi.nlm.nih.gov)

When extraintestinal symptoms are dominant, when very rapid onset is critical, or in certain older Crohn’s disease populations, anti‑TNF or other advanced therapies may still be preferred. (wjgnet.com)

FAQs

How long does vedolizumab take to work?

Many patients notice some improvement within 2–6 weeks, especially in ulcerative colitis.
For Crohn’s disease or for those who have already tried other biologics, meaningful benefit may not be clear until 10–14 weeks, and remission rates can continue to improve over the first 6 months. (wjgnet.com)

Is vedolizumab “safer” than anti‑TNF drugs?

The answer depends on what “safer” means:

• Large studies show no higher overall risk of serious infections or cancer compared with anti‑TNF therapy, and a lower serious infection risk in ulcerative colitis in some analyses. (pubmed.ncbi.nlm.nih.gov)

• In older adults, vedolizumab may reduce infection‑related hospitalizations in some datasets, though other studies suggest more IBD‑related treatment failure than with anti‑TNF agents, especially in Crohn’s disease. (pubmed.ncbi.nlm.nih.gov)

Safety comparisons therefore depend on age, disease type, prior therapies, and personal risk factors.

Can vedolizumab be used with other IBD medications?

In practice, vedolizumab is often combined with:

• 5‑ASA (mesalamine) in ulcerative colitis

• Short‑term steroids during induction

• Sometimes thiopurines or methotrexate, although combination immunosuppression is less essential than with anti‑TNF agents, and many clinicians favor vedolizumab monotherapy to limit cumulative immune suppression. (pubmed.ncbi.nlm.nih.gov)

Specific combinations and tapering plans are individualized.

What happens if a vedolizumab dose is late or missed?

Product information for the subcutaneous form advises giving the missed dose as soon as possible and then resuming the every‑2‑week schedule. Similar principles are used for IV infusions, adjusting appointment timing to get back on track. (drugs.com)

Care teams generally track symptoms, blood markers, and stool tests if doses are significantly delayed, and may repeat induction‑style dosing or adjust intervals if control is lost.