Outdated Crohn’s Disease Medications: What’s Changed from Older to Newer Treatments?

Crohn’s disease is a chronic autoimmune condition that affects the gastrointestinal (GI) tract. Symptoms can come and go, with periods that are worse (flare-ups) and times when symptoms improve or go away (remission). Treatment typically includes medications to manage symptoms during flares and to help maintain remission once it’s achieved.

There are several types of medications for Crohn’s disease. Some reduce inflammation broadly, while others, such as biologics, work in more targeted ways. Over time, newer treatments have replaced some older ones because they work better or cause fewer side effects. But cost and insurance coverage are also important considerations.

Crohn’s disease treatment isn’t one-size-fits all, and your treatment plan may change over time. But knowing the difference between older and newer options can help you make informed decisions with your healthcare team.

Early medication classes

Some of the medications once central to managing Crohn’s disease are now used less often — or only in specific situations. That doesn’t mean they no longer have a place in managing Crohn’s disease. But some older therapies have been replaced by newer options that work in a more targeted way and carry fewer long-term risks.

Corticosteroids

Corticosteroids like prednisone, methylprednisolone (Medrol), and budesonide (Entocort EC) were once the mainstay of Crohn’s disease treatment. Today, they’re still commonly used during flare-ups because they work quickly to reduce inflammation and improve symptoms.

Corticosteroids, though, are no longer recommended for long-term use because of side effects such as:

• Bone loss

• High blood pressure

• Type 2 diabetes

• Weight gain

EXPERT PICKS: WHAT TO READ NEXT

• Biologic options: Compare biologic medications for Crohn’s disease, including how they work and where they typically fit into a treatment plan.

• Oral medications for Crohn’s disease: Pharmacists discuss Crohn’s disease medications you can take by mouth, from aminosalicylates and corticosteroids to immunomodulators.

• Tired of infusions? If you’re receiving Remicade (infliximab) but you’re looking for a more convenient option, ask your prescriber about Zymfentra (infliximab-dyyb), an under-the-skin injection.

Once symptoms improve after a flare-up, corticosteroids are usually tapered off and replaced with other medications to maintain remission.

Aminosalicylates

Aminosalicylates, such as sulfasalazine (Azulfidine) and mesalamine (Lialda, Pentasa), were once commonly used for Crohn’s disease — even though they’re not FDA approved to treat it. These medications primarily work in the colon, making them effective options for ulcerative colitis. But this limits their usefulness for Crohn’s disease, which can affect any part of the GI tract.

Research has shown that aminosalicylates don’t help most people with Crohn’s disease achieve or maintain remission, especially if the condition extends beyond the colon. So, they’re no longer recommended for routine treatment. But sulfasalazine may still be an option for Crohn’s disease limited to the colon.

Immunomodulators

Immunomodulators, such as azathioprine (Imuran), 6-mercaptopurine (Purinethol), and methotrexate (Trexall), have been used to treat Crohn’s disease for decades. They help calm the immune system, reduce inflammation, and support healing. They’re considered steroid-sparing medications, meaning that they can help reduce the need for long-term corticosteroid use.

While they’re still used, immunomodulators are now less common as standalone treatments. This is because they’re slower to work and generally not as effective as biologics. They also require regular blood tests to monitor for side effects such as liver damage or low blood counts.

As a result, many healthcare professionals now prefer newer, more targeted therapies. But immunomodulators can still play an important role, especially when combined with other treatments. Situations where they may be used include:

• Maintaining remission in people with mild-to-moderate Crohn’s disease or who can’t tolerate biologics

• Supporting biologic treatment to help prevent the body from making anti-drug antibodies (proteins that block or weaken the effects of biologics)

• Managing complications such as fistulas, especially when other options haven’t been effective

Older biologics

Biologics are complex medications made using living systems, such as yeast or animal cells. They come as injections and/or infusions. Unlike medications that have broader effects in the body, they work by targeting specific parts of the immune system involved in Crohn’s disease inflammation.

Older biologics like infliximab (Remicade) and adalimumab (Humira) were major breakthroughs in Crohn’s disease treatment. They work by targeting tumor necrosis factor (TNF), a key driver of inflammation. They’re still widely used today, often as first-choice biologic options for moderate-to-severe Crohn’s disease.

But not all anti-TNF biologics are used equally. Certolizumab pegol (Cimzia) tends to be used less often because it may not be as effective as other options. It’s typically reserved for people who haven’t responded to or can’t tolerate other biologics.

Natalizumab (Tysabri) is another older biologic for Crohn’s disease. It works by blocking integrin, a protein found on immune cells. But it’s now rarely used because it has a risk of a serious brain infection called progressive multifocal leukoencephalopathy.

Shift to modern therapies

Treatment for Crohn’s disease has shifted toward more targeted medications that improve long-term outcomes with fewer side effects. Newer options include biologics beyond anti-TNF drugs, biosimilars, and targeted small molecule (chemical-based) medications.

Newer biologics

Older biologics like infliximab and adalimumab are often used first for Crohn’s treatment. They’ve been around for a long time and work well for many people. But they can lose their effect over time or cause side effects that some people can’t tolerate.

When this happens, there are newer biologics available that work in different ways, including:

• Vedolizumab (Entyvio)

• Ustekinumab (Stelara)

• Risankizumab (Skyrizi)

• Guselkumab (Tremfya)

• Mirikizumab (Omvoh)

These newer medications target specific parts of the immune system, such as integrins or interleukins, to reduce inflammation more precisely. This gives people more options if older treatments stop working or cause issues.

Biosimilars

Compared to other Crohn’s disease medications, biologics can have higher costs. This can make it difficult for some people to access them. But today, lower-cost alternatives called biosimilars are now available.

Biosimilars are highly similar versions of existing biologic medications. They’re designed to provide the same effectiveness and safety at a lower cost. Biosimilars aim to help drive down prices, making biologic therapy more affordable and accessible. Examples include:

• Humira biosimilars, such as Amjevita (adalimumab-atto) and Cyltezo (adalimumab-adbm)

• Remicade biosimilars, such as Avsola (infliximab-axxq) and Inflectra (infliximab-dyyb)

• Stelara biosimilars, such as Wezlana (ustekinumab-auub) and Selarsdi (ustekinumab-aken)

Over the last decade, the FDA has approved many biosimilars for Crohn’s disease. But most of them haven’t been available in the U.S. until more recently — and there’s more on the way.

Small molecule inhibitors

Upadacitinib (Rinvoq) is a Janus kinase (JAK) inhibitor and the first oral small molecule drug approved specifically for moderate-to-severe Crohn’s disease. Unlike older non-biologic treatments, Rinvoq targets a specific immune signaling pathway to reduce inflammation more precisely.

Rinvoq is taken by mouth, offering a convenient alternative for people who don’t want injections. It may be an option for people who haven’t responded to biologics. But it does require regular monitoring for side effects, such as infections or lab work changes.

How to decide which options are best for you

Your care team will help create a treatment plan that works best for you. This can look different from person to person. Factors they may consider include:

• Disease severity and location: Some medications are better suited for mild-to-moderate Crohn’s disease, while others may be preferred for more severe cases. The parts of the GI tract that are affected can also influence which treatment(s) are chosen.

• Previous treatments: If older medications worked well for you in the past, your prescriber may continue them. But if they caused side effects or didn’t help enough, a new option may be a better fit.

• Side effects: All medications carry some risk of side effects. Your prescriber will weigh the benefits and risks based on your health history, current symptoms, and any side effects you’ve experienced before.

• Cost and accessibility: Older medications are generally less expensive and may be more widely covered by insurance. Biologics can cost more. But if a biosimilar is available, it can offer cost savings with similar benefits.

• Injections vs. pills: Some treatments are given by injection or infusion, while others come as pills that you take by mouth. Talk to your prescriber about what works best for your comfort and lifestyle.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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