Anti-integrin Therapy

Anti-integrin therapy targets the “homing” signals that bring white blood cells into the gut. The lead medicine is vedolizumab, a gut‑selective biologic with a strong safety record in adults with moderate to severe ulcerative colitis and Crohn’s disease. It is often chosen when infection risk is a concern, and it now has both intravenous and subcutaneous options in the United States. (pubmed.ncbi.nlm.nih.gov)

Key takeaways

• Vedolizumab blocks α4β7 integrin, which guides immune cells into gut tissue, and has limited activity outside the intestine. (takeda.com)

• It is effective for induction and maintenance in ulcerative colitis and Crohn’s disease, though response can take up to about 14 weeks. (pubmed.ncbi.nlm.nih.gov)

• U.S. dosing: IV at weeks 0 and 2, then either IV every 8 weeks or switch to 108 mg subcutaneous every 2 weeks; stop by week 14 if there is no benefit. (drugs.com)

• Serious infection risk is low overall, with observational data suggesting equal or lower risk than anti‑TNF drugs in ulcerative colitis. (pubmed.ncbi.nlm.nih.gov)

• In pregnancy, registry data show no increase in adverse maternal or infant outcomes with vedolizumab. (pubmed.ncbi.nlm.nih.gov)

What anti‑integrins are

Anti‑integrins are monoclonal antibodies that block cell‑surface proteins called integrins. Vedolizumab targets α4β7 integrin, preventing it from binding mucosal addressin cell adhesion molecule‑1 (MAdCAM‑1). This limits lymphocyte entry into the gut lining, which dampens intestinal inflammation while largely sparing the rest of the body. This gut selectivity explains the favorable infection profile. (takeda.com)

A related drug, natalizumab, blocks α4 integrins system‑wide and can carry a risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection. Because of that risk, it is rarely used for IBD today. (fda.gov)

Vedolizumab at a glance

• Indications: adults with moderately to severely active ulcerative colitis or Crohn’s disease. In the European Union it is also approved for chronic pouchitis; in the United States it is not. (ema.europa.eu)

• Route: intravenous (IV) or subcutaneous (SC). SC is approved in the U.S. for maintenance after IV induction (UC since September 27, 2023, CD since April 18, 2024). (takeda.com)

• Who it suits: people prioritizing a strong safety profile, older adults, and those with infection concerns. It may be less helpful for symptoms outside the gut because its action is gut‑selective. (pubmed.ncbi.nlm.nih.gov)

How well does it work

Pivotal trials established efficacy. In ulcerative colitis (GEMINI 1), clinical response at week 6 was 47% with vedolizumab versus 26% with placebo, and 42% to 45% achieved remission at week 52 with ongoing treatment versus 16% on placebo. (pubmed.ncbi.nlm.nih.gov)

In Crohn’s disease (GEMINI 2), remission at week 52 occurred in 36% to 39% on vedolizumab versus 22% on placebo among induction responders. Early remission at week 6 was modest, which reflects a slower onset in Crohn’s. (pubmed.ncbi.nlm.nih.gov)

Guidelines now position vedolizumab among higher‑efficacy choices for treatment‑naïve moderate to severe ulcerative colitis. After prior biologic exposure, especially after anti‑TNF failure, other agents may outperform it. Treatment selection should consider disease history and safety needs. (gastro.org)

Time to response varies. Some respond by week 6, but improvement often continues through weeks 10 to 14. Lack of benefit by week 14 should prompt a switch. (wjgnet.com)

Dosing and how it is given

• Induction: 300 mg IV at weeks 0 and 2.

• At week 6: continue IV 300 mg every 8 weeks, or switch to SC 108 mg every 2 weeks starting at week 6.

• Dose‑intensification to IV every 4 weeks is sometimes used if response fades.

• Stop if there is no evidence of benefit by week 14. (drugs.com)

Practical tips
- Infusions take about 30 minutes. Most patients do not need premedication.
- The SC pen allows home maintenance injections after training. (drugs.com)

Safety and monitoring

Overall infection and malignancy rates are low, and no PML signal has been seen with vedolizumab to date, although clinicians remain alert because of the class history with natalizumab. Serious infusion reactions are uncommon. Standard pre‑biologic screening for infections and baseline labs still apply. (drugs.com)

Comparative safety
Large observational studies show similar or lower risks of serious infections with vedolizumab compared with anti‑TNF agents, with the clearest advantage in ulcerative colitis and in some older adult cohorts. Effectiveness may be lower than anti‑TNF drugs for older adults with Crohn’s disease, which is a trade‑off to discuss. (pubmed.ncbi.nlm.nih.gov)

Vaccination
Ideally, complete needed vaccines before starting therapy. Inactivated vaccines are safe during treatment. Most guidelines advise avoiding live vaccines while on immunosuppressive therapy. (cdc.gov)

Pregnancy and breastfeeding
Prospective registry data (PIANO) show no increase in adverse pregnancy or infant outcomes with vedolizumab exposure compared with no biologic or anti‑TNF therapy. Continuing effective therapy through pregnancy is recommended to prevent flares. (pubmed.ncbi.nlm.nih.gov)

Combination therapy and drug levels
Immunogenicity is low with vedolizumab, so routine combination with thiopurines is not clearly beneficial and guidelines make no firm recommendation. Drug‑level testing may help in select cases, but target thresholds are still evolving. (guidelinecentral.com)

How it compares within the class

(takeda.com)

Investigational and other gut‑selective agents (for example, etrolizumab [β7] and ontamalimab [anti‑MAdCAM‑1]) have reported mixed or discontinued programs and are not approved in the U.S. (roche.com)

FAQs

Who is a good candidate for vedolizumab

Adults with moderate to severe ulcerative colitis or Crohn’s disease who value a strong safety profile, including older adults or those with infection concerns, are often considered. Prior biologic history and disease location still guide the choice. (gastro.org)

How fast does it work

Some feel better by week 6, but full benefit can take 10 to 14 weeks. If there is no improvement by week 14, clinicians usually switch therapy. (wjgnet.com)

Can vedolizumab help joint or skin symptoms

Because its action is gut‑selective, it may be less helpful for extraintestinal symptoms such as certain joint or skin conditions. Another class may be preferred when those symptoms dominate. (takeda.com)

Is pouchitis treated with vedolizumab

In the European Union, vedolizumab is approved for chronic pouchitis. In the United States, its labeled indications are ulcerative colitis and Crohn’s disease only. (ema.europa.eu)

What vaccines are recommended

Inactivated vaccines, including influenza, pneumococcal, hepatitis A and B, HPV, COVID‑19, and the recombinant shingles vaccine, are recommended. Live vaccines are generally avoided during biologic therapy. (cdc.gov)