What Are Biologics and Small Molecules for Ulcerative Colitis?

When you have ulcerative colitis, your immune system starts to trigger inflammation in your colon. Over time, if it isn’t treated, it can cause problems in your digestive tract and increase your risk for colon cancer and other complications.

Fortunately, biologics and small molecules can treat moderate to severe ulcerative colitis by tamping down inflammation. They do this by targeting specific parts of your immune system responsible for the disease.

Gastroenterologist Suresh Pola, MD, shares how biologics work and why you may want to consider them as a possible treatment.

How do biologic and small molecule medications treat ulcerative colitis?

Biologics are medications made from living cells or antibodies. They’re used to treat a variety of diseases, from cancer and blood disorders to other autoimmune conditions.

Biologics for ulcerative colitis target specific proteins inside your body’s immune system and disrupt their ability to inflame your colon. You get them through injections or IV infusions. They’re administered at regular intervals, anywhere from two to eight weeks apart, depending on the type you’re taking and how far along you are in your treatment plan.

Small molecules are a newer type of pill. You take them by mouth to treat ulcerative colitis. They work inside your cells to reduce colon inflammation.

“The task for the biologics and small molecules is to try to reduce the inflammation so you feel better,” says Dr. Pola. “Your immune system is a good thing because it fights off infection, so you don’t want to get rid of it entirely. But biologics and small molecules can reduce flare-ups by blocking just small parts.”

Benefits of advanced therapies for ulcerative colitis

Advanced therapies like biologics and small molecules can be a powerful option for managing ulcerative colitis. They offer benefits that go beyond short-term symptom relief. By targeting the underlying inflammation in your gut, these medications can help reduce the severity of flare-ups and their frequency, making day-to-day symptoms more manageable. For some people, they can also ease issues outside the digestive tract — like joint pain — helping you feel better overall.

Over time, biologics and small molecules may help you achieve and maintain long-term remission, giving your body a chance to heal and your routine a sense of normalcy again. Advanced therapies may even help lower your colon cancer risk by keeping ulcerative colitis inflammation well-managed.

Maybe most importantly, many people find that with better symptom management comes a meaningful improvement in quality of life — more energy, fewer disruptions and the ability to focus on the things that matter most to them.

“It’s possible to be on an advanced therapy and not have a flare-up for many years,” notes Dr. Pola.

Advanced therapies offer a safer, long-term solution to treating ulcerative colitis when other treatments aren’t working as expected. Biologics and small molecules are also more targeted and controlled than other immunosuppressants that calm your entire immune system.

“Not everyone responds well to anti-inflammatory medications like mesalamine or corticosteroids like prednisone,” he continues. “Corticosteroids, in particular, are only meant for short-term use because they raise your risk for serious side effects the longer you take them.”

Side effects of advanced therapies

Side effects vary depending on the type of medication you’re taking. As they target your immune system, there’s always an increased risk for infections.

Other short-term side effects include:

• Fever
• Rash
• Nausea
• Headaches
• Joint pain

Although rare, you may also be at higher risk for certain kinds of cancer.

“Whenever we consider side effects of a medication, we should also consider the side effect of not taking the medication,” says Dr. Pola. “It’s always important to understand that usually the positives can outweigh the negatives.”

Types of biologics used to treat ulcerative colitis

Over the years, scientists have been able to create different kinds of biologics that treat ulcerative colitis. They all do roughly the same thing, but they target different parts of your immune system in different ways. Here are some of the most common types of biologics for ulcerative colitis.

Anti-TNF inhibitors

Biologics, like infliximab (Remicade®) and adalimumab (Humira®), target a specific protein responsible for chronic inflammation. People taking anti-TNF agents tend to improve within six to eight weeks.

“Anti-TNFs work at a somewhat broader level of the immune system than newer biologics, so these can have more side effects,” reports Dr. Pola. “However, they remain an important treatment for many people living with ulcerative colitis.”

Integrin receptor antagonists

Vedolizumab (Entyvio®) and others block specific white blood cells from binding to your gut, where they could cause inflammation.

“These are more selective in their targets,” says Dr. Pola.

Interleukin inhibitors

Biologics like ustekinumab (Stelara®), guselkumab (Tremfya®) and risankizumab (Skyrizi®) block signaling proteins (called cytokines) to disrupt the inflammatory response that could be causing ulcerative colitis.

“These newer medications require minimal monitoring and are very well tolerated,” says Dr. Pola.

Small molecules

Medications like upadacitinib (Rinvoq®) and etrasimod (Velsipity®) are examples of new treatments for ulcerative colitis. These small molecules are made in a lab, not synthesized from living cells.

Upadacitinib blocks specific enzymes, while etrasimod traps the cells that would cause inflammation in lymph nodes.

“Upadacitinib has the added benefit of working quickly,” explains Dr. Pola. “Some people note improvements in symptoms after the first day or two of use.”

Even though small molecules are more convenient, they still have the potential for side effects.

“Each generation of these medicines has gotten better because they’ve become more targeted with more convenient dosing,” he adds. “It’s always good to have more options because there’s no guarantee that any one is going to work. So, if one doesn’t work, we can switch to a different one.”

Should you try biologics or small molecules?

“If ulcerative colitis is mild to moderate, we start with non-biologic medications like mesalamine (Delzicol®), which can be oral or topical,” says Dr. Pola. “If those aren’t tolerated or don’t work, or if you have moderate-to-severe ulcerative colitis, you may want to try an advanced therapy.”

Biologics and small molecules are long-term medications. That means you’ll take them for as long as they’re working. In some cases, you might find success taking more than one advanced therapy if one is not enough to get you into remission.

“It’s important to take medications as prescribed and not miss doses,” emphasizes Dr. Pola. “Missed doses can allow our bodies to form antibodies against the medication and make it ineffective.”

Continue to follow up with your healthcare provider regularly. Notify them of any changes in your symptoms. They can answer any other questions you may have, too.