The Pros and Cons of Biologics for Ulcerative Colitis

Over the past 15 years, treatment options for ulcerative colitis (UC) have expanded quite a bit. Among the newer options is a class of drugs called biologics.

Biologics are derived from natural sources, such as human or animal genes or microorganisms, and are designed to act on the immune system, specifically the parts that play key roles in fueling inflammation.

“As inflammation is thought to be a cornerstone of the process involved in the manifestation of inflammatory bowel diseases, like Crohn’s disease and ulcerative colitis, they have proved to be very effective as treatment for certain patients,” says Donald Tsynman, MD, a gastroenterologist at NewYork-Presbyterian Hospital in New York City.

The fact that biologics target the activity of the patient’s own immune system is what sets them apart from some other medications for ulcerative colitis, Dr. Tsynman says.

How Biologics Work

“The biologics that have been approved for Crohn’s and ulcerative colitis involve antibodies that are developed in the lab to target proteins related to inflammation,” says Joel Pekow, MD, a gastroenterologist and an associate professor of medicine at the University of Chicago.

The biologics that are now approved by the U.S. Food and Drug Administration (FDA) for treating ulcerative colitis include:

• Humira (adalimumab)
• Simponi (golimumab)
• Remicade (infliximab)
• Entyvio (vedolizumab)
• Stelara (ustekinumab)

Many biologics, including Humira, Simponi, and Remicade, work by targeting a protein called tumor necrosis factor alpha (TNF-alpha), which contributes to inflammation.

Another way that biologics target inflammation is by addressing the problem of too many white blood cells in the GI tract. Entyvio works this way — it blocks these inflammatory cells from getting to the site of inflammation.

A review published in October 2019 in the United European Gastroenterology Journal examined the safety and efficacy of Humira, Simponi, Remicade and Entyvio, and found that all four biologics were effective at treating moderate to severe ulcerative colitis, and all were comparatively safe.

Stelara is the new biologic on the block. While the drug has been on the market since 2009 for the treatment of Crohn’s disease, psoriatic arthritis, and psoriasis, it was only approved in 2019 for the treatment of ulcerative colitis.

The new approved use for Stelara was based on results of a clinical trial published in September 2019 in the New England Journal of Medicine that found Stelara could safely and effectively induce and maintain remission in adults with moderately to severely active ulcerative colitis.

Stelara works by blocking interleukin-12 and interleukin-23, immune proteins known to be involved in immune responses in inflammatory bowel disease and other immune-mediated conditions.

RELATED: 10 Things to Know About Biologics for Ulcerative Colitis

The Advantages of Biologics for Ulcerative Colitis

Biologics can improve gut symptoms, bringing about and maintaining remission (preventing flares) in people with moderate to severe ulcerative colitis. They can also reduce the need for hospitalization and surgery, says the British organization Crohn’s & Colitis UK.

One key advantage of biologic therapies over other types of treatment for ulcerative colitis is that their mechanisms of action are more precisely targeted to the factors responsible for the condition, notes the Crohns & Colitis Foundation.

Unlike corticosteroids, for example, which affect the whole body and may produce major side effects, biologic agents act more selectively. These therapies are targeted to particular proteins that have already been proven to be involved in ulcerative colitis.

“Patients are often nervous about biologics,” says Laura Raffals, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota. “But they’re not as scared about taking a corticosteroid, and that’s an important conversation to have because the data shows that patients on biologics are much safer and stay in remission longer. The serious side effects we see are from steroids or narcotics, not biologics. ”

The Potential Downsides of Biologics

While biologics may be a promising option for treating your ulcerative colitis, not every drug is suited to every patient.

“We will work with patients for a while to tailor a treatment plan that is right for them,” says Dr. Raffals. “That may mean trying different biologics and small-molecule drugs, and, of course, taking into account what the patient’s insurance will cover.”

A person’s lifestyle, demographic factors, and the severity of the disease are all considerations in the choice of whether or not to use biologics, and which of them is the best option.

Some potential downsides of taking biologics include:

• Lack of long-term data While studies and clinical information indicate that biologics are generally safe, they are relatively new drugs, so — with the exception of Remicade (infliximab) — long-term safety information is not available.
• Cost Because most of these drugs are available only as name brands, they can be very expensive. The introduction of biosimilars — medicines that are very similar to an original biologic therapy that has come off patent — has increased competition in the biologics market and is helping to bring down the cost of this type of therapy.
• Method of treatment Taking biologics isn’t as simple as swallowing a pill. Some biologics, such as Humira, can be self-administered via an at-home injection, while others, like Entyvio, require intravenous infusion. Your level of comfort or schedule may influence your choice between biologics, or whether to take them at all.
• Side effects As with all medications, biologics come with potential side effects. These include: soreness at the injection site, aches and pains, fever, and increased susceptibility to infection.

If you’re considering biologics for treatment, speak to your doctor to find out what’s best for you. As Tsynman says, “At the heart of the decision is the relationship between the patient and the physician and specifically exploring what works best for each individual. ”

Additional reporting by Jordan M. Davidson.

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Types, side effects, cost, and more

Doctors may prescribe biologics to treat ulcerative colitis. Biologics are medications that companies make from living cells. They attack certain cells and proteins in the immune system responsible for inflammatory conditions.

Ulcerative colitis (UC) is a condition that affects the digestive tract. A person with UC has an overactive immune system that causes inflammation in the intestines.

Biologic medications can be an effective alternative to help control the symptoms of UC, which can worsen sporadically in periods known as “flare-ups” or “flares.”

Scientists and drug manufacturers make these medications from specially engineered living cells or antibodies. After growing the cells in a laboratory, scientists extract special proteins and use these to make each drug. These proteins then operate by targeting a particular receptor found on immune cells.

Doctors use different biologics to treat a variety of conditions, including cancer and several autoimmune disorders.

The following is a summary of the potential advantages and disadvantages of using biologics to treat UC:

Pros

• directly attack cells and proteins responsible for UC inflammation
• alternative for 20–40% of people who do not respond to typical treatments such as 5-aminosalicylates or corticosteroids
• may reduce surgery risk

Cons

• can be expensive
• a person may need to inject them, which can be challenging or uncomfortable
• may stop working over time
• raise the risk of infection

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This article describes the types of biologics that may help treat UC. We also look into their side effects and costs.

In a person with UC, the immune system is overactive and mistakenly attacks cells in the body.

Biologics are medications that attack specific cells and proteins in the immune system that cause inflammatory disease processes. For this reason, doctors also refer to treatment with biologics as targeted therapy.

Usually, a doctor would prescribe biologics to treat adults who have moderate-to-severe UC. There are different types of biologics that may fit a person best on the basis of their symptoms. These include:

• anti-tumor necrosis factor (TNF) agents
• integrin receptor antagonists
• interleukin inhibitors
• Janus kinase (JAK) inhibitors

Anti-TNF agents can help treat UC in adults by reducing symptoms and helping to heal inflamed tissues.

These drugs target the protein tumor necrosis factor-alpha, which promotes inflammation and may be responsible for the development of UC.

People with UC usually see improvements in their symptoms within 8 weeks of starting treatment with an anti-TNF agent. Some people experience more immediate results.

Types of anti-TNF agents

Different types of anti-TNF agents may help treat UC. These include:

Generic name	Brand name	Dosage
adalimumab	Humira	Four injections, 160 milligrams (mg) each. 2 weeks later: Two injections, 80 mg each. From then on: One injection, 40 mg every 2 weeks.
adalimumab-atto	Amjevita	Four injections, 160 mg each. 2 weeks later: Two injections, 80 mg each. From then on: One injection, 40 mg every 2 weeks.
adalimumab-adbm	Cyltezo	Four injections, 160 mg each. 2 weeks later: Two injections, 80 mg each. From then on: One injection, 40 mg every 2 weeks.
golimumab	Simponi	Two starter doses. From then on: Every 4 weeks.
infliximab	Remicade	Intravenous infusion. First three doses at 0, 2, and 6 weeks. From then on: Every 8 weeks.
infliximab-abda	Renflexis	Intravenous infusion. First three doses at 0, 2, and 6 weeks. From then on: Every 8 weeks.
infliximab-dyyb	Inflectra	Intravenous infusion. First three doses at 0, 2, and 6 weeks. From then on: Every 8 weeks.
infliximab-qbtx	IXIFI	Intravenous infusion. First three doses at 0, 2, and 6 weeks. From then on: Every 8 weeks.

Adalimumab

A doctor may prescribe adalimumab (Humira) if a person did not respond well to other immune suppressors, such as corticosteroids, azathioprine (Imuran), or 6-mercaptopurine (Purinethol).

In a clinical study, more than 17% of participants with UC who took adalimumab experienced remission after 52 weeks of the treatment.

A person can self-administer the injections at home after receiving instructions from a healthcare professional.

Golimumab

A doctor may prescribe golimumab (Simponi) for people who need continuous steroid treatment or for people who have not found other UC medications effective.

In a clinical trial, after 6 weeks, more people from the group that took golimumab than those from the group who did not experience:

• a response to the treatment
• a remission of UC symptoms
• improvements in the appearance of the intestines on endoscopy imaging

If the body responds to this treatment, a person can keep taking it to maintain remission.

Another trial showed that participants had maintained remission after the 30th and 54th weeks of treatment.

A person can self-administer these injections at home after receiving instructions from a healthcare professional.

Infliximab

A doctor may prescribe infliximab (Remicade) if a person with UC did not benefit from other treatments.

Infliximab is the only anti-TNF agent that a doctor can prescribe to children with UC, starting from the age of 6 years.

In clinical studies, adult and pediatric participants experienced remission and healing of the intestinal wall with this treatment.

A doctor may prescribe the integrin receptor antagonist vedolizumab (Entyvio) for adults with moderate to severe UC.

This drug can be suitable for people with an intolerance to anti-TNF agents or people who did not find these drugs to be effective. It may also benefit people with a dependence on corticosteroids.

Vedolizumab may start to have noticeable benefits after 6 weeks.

In clinical studies, more people in the treatment group achieved remission after 52 weeks than those in the control group. In the treatment group, the researchers also found improvements in the appearance of the intestines.

Dosage

The typical dose per infusion is 300 mg. A person will have their next infusions at 2 and 6 weeks. From then on, they will get a transfusion every 8 weeks.

Ustekinumab (Stelara) is an antibody that blocks two proteins and signaling molecules that doctors call interleukin-12 and interleukin-23.

Both play an important role in the inflammatory and immune responses and contribute to chronic inflammation that is associated with UC.

Ustekinumab is suitable for adults with the condition. It may lead to remission after 8 weeks, and in clinical studies, researchers found that this treatment led to improvements in the appearance of the intestines.

Dosage

For the first dose, a person has 6 mg for each kilogram that they weigh. The doctor will decide on the best approach after that.

In 2019, tofacitinib (Xeljanz) was the first biologic medication to gain Federal Drug Administration (FDA) approval to treat UC. It targets JAK proteins and blocks their activity. A second JAK inhibitor, upadacitinib (Rinvoq), gained approval for treating UC in March 2022.

JAK proteins send signals that promote the activity of the immune system. Blocking these proteins stops or slows certain immune functions.

Doctors may prescribe tofacitinib to people with moderate to severe UC that has not responded well to other treatments. People with an intolerance to anti-TNF agents may benefit from this approach.

In one study, 60% of participants who took tofacitinib had improvements in their UC symptoms after 8 weeks. They also experienced less bleeding from their rectums after 2 weeks.

In 7% of participants in the treatment group, researchers observed improvements in the appearance of the intestines, compared with 3% of the placebo group.

Dosage

This drug is available as a pill. A doctor may prescribe 10 mg twice a day for 8 weeks. If the treatment appears to be effective, they may lower the dosage to 5 mg twice a day going forward.

Like all drugs, biologics can cause side effects.

People have to inject many of these medications, and at the site of the injection, a person may experience:

• redness
• itchiness
• bruising
• pain
• swelling

Other side effects of biologics include:

• headache
• fever
• chills
• hives
• rashes

Side effects of tofacitinib may differ from those of injectable biologics. A person may experience:

• diarrhea
• headache
• high or low blood pressure

Allergic reactions can also occur, and they may cause symptoms such as hives and difficulty breathing. In rare cases, a person may experience anaphylaxis.

If a side effect is bothersome or may indicate an allergic reaction, a person should contact a doctor. If any side effect is concerning or severe, they should dial 911 or otherwise contact emergency services.

Anaphylaxis is a severe allergic reaction that can be life threatening. The symptoms develop suddenly and include:

• hives
• swelling of the face or mouth
• wheezing
• fast, shallow breathing
• a fast heart rate
• clammy skin
• anxiety or confusion
• dizziness
• vomiting
• blue or white lips
• fainting or loss of consciousness

If someone has these symptoms:

1. Check whether they are carrying an epinephrine pen. If they are, follow the instructions on the side of the pen to use it.
2. Dial 911 or the number of the nearest emergency department.
3. Lay the person down from a standing position. If they have vomited, turn them onto their side.
4. Stay with them until the emergency services arrive.

Some people may need more than one epinephrine injection. If the symptoms do not improve in 5–15 minutes, or they come back, use a second pen if the person has one.

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Before prescribing a biologic, a healthcare professional should describe the risks in detail. Some include:

• Arthritis: Anti-TNF agents can help treat some causes of joint pain, but they can also cause new joint pain in some cases.
• Liver problems: In rare cases, biologics have links with liver problems. Anyone who notices yellowing of the eyes or skin while taking these medications should receive medical attention straight away.
• Lupus-like reactions: These reactions to anti-TNF treatment are rare. A person should stop the treatment and contact a doctor if a rash, joint pain, fever, or muscle aches develop.
• Cancer: While the risk is low, researchers have found some associations between anti-TNF agents and lymphoma.

Because biologics affect the immune system, a person taking this type of medication may have an increased risk of infections, some of which can be severe. For this reason, it is important for a person to take the necessary vaccinations, including those for:

• influenza
• pneumonia
• hepatitis

A person should contact a healthcare professional immediately if a new cough, a fever, or any other flu symptoms develop.

Interactions with other medications

Interactions between biologics and other medications can be significant, and each type of biologic drug can present different risks.

A doctor should be aware of all the over-the-counter or prescription medications, and all the supplements, herbal medications, and vitamins that a person takes before they prescribe a biologic.

Anyone using a biologic for UC should speak with a doctor before receiving a vaccine. For people who use certain biologic medications, including golimumab, infliximab, and adalimumab, having a live vaccine can be dangerous, and doctors recommend avoiding it.

Biologics can be expensive. According to research from 2018, this type of treatment costs $10,000–30,000 per year on average, and the more expensive types can cost more than $500,000 annually.

Although many medical insurance plans may cover biologics, depending on a person’s deductible, the cost can still be high.

A doctor may instead recommend a type of drug they call a “biosimilar.” There is very little clinical difference between these drugs and biologics. Biosimilars are less expensive but just as safe and effective.

The FDA approved the use of biosimilars in an effort to reduce costs. However, the FDA does not regulate whether insurance companies cover the costs of these drugs.

The following table provides an overview of biologics available to treat UC. The abbreviation “IV” stands for “intravenous.”

A range of biologic drugs can reduce UC symptoms in adults and help achieve remission. For children with moderate to severe UC, a doctor may prescribe infliximab.

Biologics are effective because they target the specific factors in the immune system that cause UC.

However, these drugs can cause side effects. It is important to discuss the risks and potential benefits of each option thoroughly with the doctor.

Below, we answer some questions that people often ask about biologics for ulcerative colitis.

How long do you take biologics for ulcerative colitis?

A person can feel better within 6–8 weeks of taking biologics, although some drugs can take more time to be effective. When considering whether to stop, a person should consult with their doctor on the basis of criteria such as the current symptom level, any medication side effects, existing comorbidities, and more.

Which biologic is safest for ulcerative colitis?

In a 2020 study, researchers found that taking vedolizumab comes with the lowest risk of infection, followed by ustekinumab.