CCFA.org: Biologics

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Biologic Therapies

The newest class of drugs to be used in IBD, these include Adalimumab (Humira®), Certolizumab pegol (Cimzia®), Infliximab (Remicade®), and Natalizumab (Tysabri®). Biologics are genetically engineered medications made from living organisms and their products, such as proteins, genes, and antibodies. Biologics interfere with the body's inflammatory response in IBD by targeting specific molecular players in the process such as cytokines—specialized proteins that play a role in increasing or decreasing inflammation. Promising targets include tumor necrosis factor (TNF)-alpha, interleukins, adhesion molecules, colony-stimulating factors, and others. Learning how these factors work has enabled researchers to design special treatment approaches that interrupt inflammation at various stages.

Biologic therapies offer a distinct advantage in IBD treatment. Their mechanism of action is targeted. Unlike corticosteroids, which tend to suppress the entire immune system and thereby produce major side effects, biologic agents act selectively. Therapies are targeted to particular enzymes and proteins that have already been proven defective, deficient, or excessive in people with IBD and in animal models of colitis.

Anti-TNF

Within the last decade, a class of biologics known as anti-TNF was introduced for use in Crohn's disease. More recently, anti-TNF has been used in ulcerative colitis. These therapies suppress part of the immune system by binding to and inactivating tumor necrosis factor alpha (TNF-alpha). TNF-alpha is a cytokine, a specialized protein that promotes inflammation in the intestine in other organs and tissues.

Infliximab (Remicade®) is the first FDA-approved biologic therapy for Crohn's disease and fistulizing Crohn's disease in adults, as well as for ulcerative colitis in adults. It is given as a drip via intravenous infusion. The medication is a chimeric monoclonal antibody. In other words, it's a hybrid consisting of 75 percent human, 25 percent mouse protein sequence. It is used for adults with moderately-to-severely active disease who have not responded well to other therapies. In Sept 2011, the FDA approved infliximab to treat ulcerative colitis in children six years and older.

Adalimumab (Humira®) was approved for use in Crohn's disease. It also binds to and inactivates tumor necrosis factor alpha, but it is a fully human monoclonal antibody. It is given by injection. It is used for adults with moderately to severely active disease who have not responded well to other therapies, and who have lost response or are unable to tolerate infliximab.

Certolizumab pegol (Cimzia®) was recently approved for use in Crohn's disease. It the first and only PEGylated anti-TNF-alpha. The antibody portion combines with a special chemical called polyethelyene glycol (PEG), which delays its excretion from the body. It is given by injection. It is used to reduce the signs and symptoms of moderately to severely active Crohn's disease in adult patients who have not been helped enough by usual treatments.

Integrin Receptor Antagonist

A recent development in biologic therapy is the development of integrin receptor antagonists. Their mechanism of action is different from the anti-TNF agents. Integrin receptor antagonists work by binding to particular cells in the bloodstream that are key players in inflammation.

Natalizumab (Tysabri®) was recently approved for use in Crohn's disease. It is a recombinant humanized monoclonal antibody thought to inhibit certain types of white blood cells that are involved in the inflammatory process. It is given by IV infusion for moderate to severely active Crohn's adult patients who have had an inadequate response to, or are unable to tolerate, conventional and anti-TNF disease therapies.

In the Pipeline

In addition, there is a "pipeline" of drugs that are in the very early stages of development. These include many more biologics with different modes of action. They are structured to interrupt the out-of-control signalling within different pathways in an immune system that simply won't shut off. By uncovering additional mechanisms, investigators expect to generate increased options for the treatment of chronic inflammatory diseases. Additional biologic therapies under investigation for IBD include alicaforsen for ulcerative colitis; thalidomide; the interleukins IL-6, IL-10, IL-11, and IL-12; interferon gamma, and GM-CSF.

Side Effects

The most common side effects with the anti-TNF agents include infusion or injection site reactions (redness, swelling, itching, bruising, rash), upper respiratory infections, headaches, rash, and nausea. Check with your doctor about other possible side effects.

Drug Interactions

People taking several different medicines, whether prescription or over-the-counter, should always be on the lookout for interactions between drugs. Drug interactions may decrease a medication's effectiveness, intensify the action of a drug, or cause unexpected side effects. Before taking any medication, read the label carefully. Be sure to tell your doctor about all the drugs you're taking—even over-the-counter medications or complementary therapies—and any medical conditions you may have.

Special Considerations

There have been some reports of serious infections associated with anti-TNF agent use, including tuberculosis (TB) and sepsis, a life-threatening blood infection. You should always have a TB skin test before you use infliximab, adalimumab, or certolizumab because these therapies can increase the risk of active TB for those who have been exposed. It's not that you will "catch" TB when taking infliximab, adalimumab, or certolizumab but if you have latent (inactive) TB, the drug can reactivate the infection. In this case, your doctor should begin TB treatment before you start these medications. The same precaution should be taken before beginning treatment with corticosteroids.
Biologics may reduce the body's ability to fight other infections as well. If you are prone to infections
or develop any signs of infection while taking these medications, such as fever, fatigue, cough,or the
flu, inform your doctor immediately.
It may be inadvisable for people with heart failure to take any of these medications, so tell your doctor if you have any heart condition before starting this medication. Inform your doctor at once if you develop new or worsening symptoms of heart failure—namely shortness of breath or swelling of the ankles or feet.
On rare occasions, blood disorders have been noted with anti-TNF agents. Inform your doctor if you develop possible signs such as persistent fever, bruising, bleeding, or paleness while taking infliximab, adalimumab, or certolizumab . Nervous system disorders also have been reported occasionally. Let your doctor know if you have or have had a disease that affects the nervous system, or if you experience any numbness, weakness, tingling, or visual disturbances while taking these medications.
Although reports of lymphoma (a cancer of the lymphatic system) in patients taking anti-TNF agents are rare, they do occur more often than in the general population.
Progressive multifocal leukoencephalopathy (PML), a rare brain infection, has been reported with
natalizumab use. Natalizumab may also cause liver damage and allergic reactions.
Patients with a medical condition that can weaken their immune system such as HIV infection or AIDS, leukemia or lymphoma, or an organ transplant should not take Natalizumab.
Your physician will monitor you closely while you are on biologic therapy. It is not advisable to stop and then try to restart anti-TNF agents. To achieve and maintain remission, it is advisable to stay on the medication.

Updated 10/3/11