Anti-integrin therapy is a specialized class of biologic medication used to manage certain autoimmune conditions. These drugs offer a targeted approach to treatment, differing from broader immunosuppressants. They work by interfering with how specific immune cells move throughout the body, aiming to reduce inflammation in affected tissues. This strategy is used to control the underlying mechanisms of chronic inflammatory disorders like inflammatory bowel disease (IBD) and multiple sclerosis (MS).
The Role of Integrins in Inflammation
Integrins are proteins found on the surface of white blood cells that function much like a docking system. These proteins allow the cells to attach to the walls of blood vessels and then migrate from the bloodstream into surrounding tissues. This process is a normal part of the body’s immune response, enabling inflammatory cells to reach sites of injury or infection.
In certain autoimmune and inflammatory diseases, this system becomes dysregulated. An excessive number of white blood cells are directed to specific areas, such as the gastrointestinal tract or the central nervous system. This constant traffic of immune cells leads to chronic inflammation and damage, such as inflammation of the intestinal lining in IBD or damage to nerve fibers in MS.
Mechanism of Action
Anti-integrin therapies work by directly interfering with the ability of white blood cells to move into sensitive tissues. These medications are monoclonal antibodies, laboratory-produced molecules engineered to attach to integrin proteins on the surface of immune cells. By binding to these proteins, the medication blocks them from attaching to blood vessel walls, which prevents them from migrating into surrounding tissues to cause inflammation.
This is a selective process, as these therapies are designed to inhibit only specific integrin types, leaving other parts of the immune system to function normally. For instance, some anti-integrin drugs primarily block cell movement into the gut, while others have a more systemic effect.
This targeted action allows anti-integrin therapy to reduce inflammation in specific locations without the widespread immune suppression of other treatments. The therapy essentially keeps inflammatory cells circulating in the bloodstream, unable to exit and cause harm in the targeted organs.
Conditions Treated with Anti-Integrin Therapy
Anti-integrin therapy is primarily used for inflammatory bowel disease (IBD) and multiple sclerosis (MS). In IBD, which includes Crohn’s disease and ulcerative colitis, the therapy is effective because it can prevent immune cells from entering the lining of the gastrointestinal tract.
Some anti-integrin medications are “gut-selective,” meaning they specifically target the integrins that guide white blood cells to the intestines. This makes them an effective treatment for moderate-to-severe Crohn’s disease and ulcerative colitis. By limiting inflammation specifically in the gut, these drugs can reduce symptoms while minimizing systemic side effects.
For multiple sclerosis, anti-integrin therapy works by preventing inflammatory cells from crossing the blood-brain barrier. This action reduces the inflammation that damages the myelin sheath covering nerve cells, which is the hallmark of MS.
Types of Anti-Integrin Medications
Several anti-integrin medications are available, each targeting specific integrin proteins.
- Natalizumab (Tysabri) targets the α4-integrin subunit. It is approved for both MS and Crohn’s disease, preventing leukocytes from crossing the blood-brain barrier and entering intestinal tissue.
- Vedolizumab (Entyvio) is a humanized monoclonal antibody that specifically targets the α4β7 integrin. This makes it a gut-selective therapy for ulcerative colitis and Crohn’s disease with fewer systemic effects.
- Etrolizumab is an investigational drug that targets the β7-integrin subunit, which affects both leukocyte trafficking and cell adhesion.
- Abrilumab is another therapy that also targets the α4β7 integrin, similar to vedolizumab.
These different medications provide options that can be tailored to the specific inflammatory pathways driving a patient’s condition.
Administration and Safety Profile
Anti-integrin medications are administered either as an intravenous (IV) infusion in a clinical setting or as a subcutaneous injection that can be self-administered at home. For example, vedolizumab is started with IV infusions at weeks zero, two, and six, followed by maintenance doses every eight weeks.
A primary concern, particularly with natalizumab, is the risk of developing progressive multifocal leukoencephalopathy (PML). PML is a rare but serious viral infection of the brain caused by the John Cunningham (JC) virus. Due to this risk, access to natalizumab is restricted through special safety programs that involve careful patient monitoring.
Gut-selective therapies like vedolizumab are considered to have a more favorable safety profile because their action is localized to the gastrointestinal tract. However, all biologic therapies carry some risk of side effects, and patients are monitored for potential reactions or infections. The choice of medication involves balancing its effectiveness for the specific condition against its potential risks.