An Overview of Biologics for Crohn’s Treatment

Biologic medical therapies, or biologics, are an important type of treatment for Crohn’s disease and inflammatory bowel disease. Biologics are a wide-ranging class of drugs, and there are many different types.

Most biologics for Crohn's disease are monoclonal antibody treatments that help tune down the immune system’s overreaction to treat symptoms and help prevent flare-ups.

These treatments have led to unprecedented improvements in the treatment of Crohn’s disease over the past two decades. But they don’t work for everyone and come with their own risks.

This article will explain what biologics are, how they can be used to treat Crohn’s disease, and the benefits and risks of using biologics for Crohn’s.

Crohn's disease is an autoimmune disease, which means the immune system starts attacking parts of the body, leading to inflammation. The inflammation in Crohn’s disease happens along the digestive tract, which runs from the mouth to the anus. It is a form of inflammatory bowel disease (IBD). 

Symptoms of Crohn’s disease include gastrointestinal distress, such as diarrhea, cramping, abdominal pain, and weight loss. Crohn’s disease is chronic, incurable, tends to return even after treatment, and can worsen over time. Treatments aim to ease symptoms.

What Are Biologics?

Biologics are a large class of treatments that take a variety of forms. Their common features are that they are large molecules created by living things.

They’re usually made up of complex molecules that our bodies use—sugars, nucleic acids, and proteins. Some biologics are even whole cells. As medical treatments, these drugs are created in the lab—cells grown in a dish, animals, or even isolated from human blood.

Traditional drugs are classified as “small molecules” because they are small in size. These drugs can often be taken orally, and they are manufactured using chemical reactions. 

In contrast, biologics are usually much larger than small molecules. They often are made to resemble proteins that naturally occur in our bodies but may have some slight modifications.

Because of their size and complexity, biologics usually need to be injected directly into a vein or under the skin to work. They aren’t the kinds of drugs you can take as a pill. 

There are many different kinds of biologics. One of the largest categories for the treatment of Crohn’s disease is the monoclonal antibody. Antibodies are large proteins that are made naturally in our bodies by our immune systems. Monoclonal means that the antibodies bind only to one substance.

Antibodies have special customizable arms that work like puzzle pieces to help them find and attach to very specific pieces of proteins. These proteins might be on viruses, bacteria, or other germs that can make us sick. The antibody attaches to the germ and acts like a flag, waving down the body’s defenses to come and destroy it.

How Biologics Can Be Used to Treat Crohn’s Disease

In autoimmune diseases like Crohn’s disease, the immune system gets confused and makes antibodies customized to the body’s own normal proteins. These are called autoantibodies and are the core cause of symptoms of autoimmune diseases like Crohn’s. 

Because Crohn’s disease is a dysfunction of the immune system, antibodies themselves have played a big role in developing new treatment approaches.

These antibody treatments are usually customized to recognize parts of the immune system that end up going out of whack when you have an autoimmune disorder. They can then be used to turn down these autoimmune overreactions.

Biologics have been used to treat Crohn's disease for about two decades now, and they've become the first line of defense against moderate to severe disease. They help people reduce symptoms, avoid complications and side effects of other drugs, and help put people into remission—lowering their risk of flare-ups.

The Benefits and Risks of Biologics for Crohn’s

Traditional therapy for Crohn’s disease includes anti-inflammatory medications (including immunosuppressive drugs, nonsteroidal anti-inflammatory drugs, or NSAIDs, and corticosteroids), anti-diarrheal medications, surgery, and a procedure known as bowel rest in which you stop eating food for a prolonged period to let your bowel heal. 

Your doctors might suggest trying a biologic if your Crohn’s is not well controlled with these medications. They can help Crohn’s patients achieve remission and remain symptom-free and flare-up-free with fewer side effects. The benefits of these treatments typically outweigh the risk for most Crohn’s patients.

Biologics like monoclonal antibodies are directly targeted to one pathway in the immune system. This means other parts of the immune system are left alone when you’re taking this treatment—leading to fewer unwanted medication side effects. 

The risks of taking biologics are relatively low. Side effects include:

• Headache
• Fever and chills
• Joint pain
• Sore throat and coughing
• Depression
• Fatigue

You may also have a reaction where you get the shot or IV. This may include pain, redness, swelling, itch, bruise, or rash. You may have an allergic reaction to the injection or infusion. 

These drugs make you more susceptible to infections, including upper respiratory infections like colds, urinary tract infections, and serious infections like tuberculosis or sepsis.

Tumor necrosis factor inhibitors, also called TNF-alpha inhibitors, are specific biologics that may increase your risk very slightly of developing lymphoma, a cancer of the white blood cells.  However, this association is still unclear.

Biologics may impact your liver function, so watch for any signs of jaundice, including yellow skin or eyes. 

There’s also a possibility these drugs might not work for you. You may need to take them for weeks before you see effects. You may need to try multiple biologics or change your dose levels or timing multiple times before finding the right ones for you. 

If you’re pregnant, your doctor may recommend stopping your treatment during your second and third trimesters. There is no known negative impact on the baby in the short term, but monoclonal antibodies can pass into the fetus's blood and reach high levels.

Types of Biologics for Crohn’s Disease

Several biologics have been approved for use against Crohn's disease. They are all monoclonal antibody therapies, but they work in a few different ways. 

Some of these therapies have “generic” versions called biosimilars. These drugs have been demonstrated to be “biosimilar to or interchangeable with an FDA-approved biological product.” They work through the same pathways but are made by different companies and may be manufactured differently but held to the same rigorous standards as other drugs approved by the Food and Drug Administration (FDA).

Biologics Targeting TNF-alpha

Tumor necrosis factor-alpha (TNF-alpha) is a protein involved in the inflammatory response that your body sets off when your immune system detects an invader. In the case of Crohn’s disease, autoimmune antibodies are set off. TNF-alpha is active in the intestine as well as other areas of the body.

By turning down this inflammation pathway, these medications can reduce Crohn’s symptoms and let the intestines start healing. The following prescription biologics target these TNF-alpha proteins as their pathways.

Humira (adalimumab):

• Approved in 2007 for Crohn's disease
• Approved for use in children ages 6 and up
• Also approved for rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis
• Two biosimilars are available: Cyltezo (Adalimumab-adbm) and Amjevita (Adalimumab-atto)
• Given as a shot under the skin using an auto-injector pen
• First injection is four times the normal dose, the second dose is two times a normal dose, then one injection is needed every two weeks
• Cost is about $2,900 per pen

Cimzia (certolizumab):

• Approved in 2007 for Crohn's disease
• Also approved for rheumatoid arthritis, plaque psoriasis, and ankylosing spondylitis
• First three doses are given every two weeks, then dosed every four weeks
• This drug is given as a shot under the skin using a syringe, either by the patient or a healthcare professional.
• Cost is about $4,693 for two syringes

Remicade (infliximab):

• Approved in 1998 for Crohn's disease
• Also approved for ulcerative colitis
• Approved for use in children ages 6 and up
• Three biosimilars are available: Renflexis (Infliximab-abda), Inflectra (Infliximab-dyyb), and IXIFI (Infliximab-qbtx)
• This drug is given through a line into your blood vessel (an IV) attached to a tube. You’ll need to visit an infusion clinic, doctor’s office, or treatment center for this drug. The infusion may take between two and four hours.
• You’ll get a first dose, a second dose two weeks later, then a third four weeks after that (so six weeks after the first dose). From there, you’ll need a dose every eight weeks.
• Remicade costs about $1,130 per vial. The costs associated with the infusion will be additional.

Biologics Targeting Integrins

Integrins are proteins involved in the movement of inflammatory immune cells from the blood vessels into the body’s tissues. The following biosimilar targets integrins.

Entyvio (Vedolizumab):

• Approved in 2014 for Crohn's disease
• Also approved for ulcerative colitis
• May help patients stop using steroids
• Might work for patients for whom anti-TNF biologics and other drugs haven’t worked
• This drug is dosed through an IV. The infusion takes about 30 minutes.
• The first dose is given, then two weeks later you’ll need another dose. The third dose is given six weeks after the first infusion (four weeks after the second). After three doses, you’ll get a dose every eight weeks.

Biologics Targeting Interleukin 12 and 23

Interleukins are proteins that are important in the body’s inflammatory response. There is only one biologic that targets interleukin 12 and 23 to help manage Crohn’s disease.

Stelara (Ustekinumab):

• Approved in 2016 for Crohn's disease
• Also approved for psoriasis and psoriatic arthritis
• First dose is given through an IV infusion. Every eight weeks thereafter, continuing doses can be given as shots under the skin either by a healthcare provider or self-injected by the patient.
• Stelara costs $23,347 per syringe.

Skyrizi (risankizumab-rzaa):

• Approved in 2022 to treat moderate to severe Crohn's disease.
• Also approved for psoriatic arthritis and moderate to severe plaque psoriasis.
• Three starting doses are given by infusion (IV) at four-week intervals, followed by injections at home every other month.
• Skyrizi costs $18,273 per dose.
  

Summary

Biologics are newer types of treatments for Crohn’s disease. These treatments use monoclonal antibodies to tune down the overacting parts of the immune system that cause the symptoms of Crohn’s disease.

There may be side effects, but the benefits usually outweigh the risks. Humira, Cimzia, Remicade, Entyvio, and Stelara are approved for the condition.

A Word From Verywell

Living with Crohn's disease can be debilitating, but getting treatment shouldn’t be. When there are so many treatment options available to choose from, it can be hard to know if you’re on the right treatment course. 

If you’re newly diagnosed with Crohn’s, talk to your doctor about your options as soon as you get diagnosed. If you’ve been responding well to the biologics you’re on, you may be able to reduce your dose. Talk to your doctor about de-escalating your treatment.

If you’re not responding well to biologics for your Crohn’s disease, or your symptoms have returned, talk to your doctor about potentially changing your dose amounts, regimen, or the type of biologic you’re on.

Frequently Asked Questions

How are biologics for Crohn’s administered? 

There are two ways most monoclonal antibodies are administered. One way biologics are administered is infusion through a line that goes directly into your bloodstream. This will need to be done at an infusion clinic and may take a few hours. 

Some biologics or biosimilars have the option of having you inject them yourself under your skin. This can be done with an auto-injector pen, or with a syringe and needle. A doctor or nurse can also inject you. 

How much do biologics for Crohn’s cost?

Biologics for Crohn’s disease are expensive. These types of drugs are difficult to develop and create, so that drives up the price. These medications should be covered by insurance, but even if you have it, you may end up paying thousands. Without insurance, the cost is even higher.

For Crohn's disease patients, a 2019 survey found that the average annual cost of treatment is almost $25,000, with about $2,300 of that coming out of the patient’s pocket. Generally speaking, biologics can cost about $20,000 a year. Your insurance might cover 75% of that cost.