New Biologics and Other Medications on the Horizon for IBD

People with Crohn’s disease and ulcerative colitis often have difficulty finding the right medication for their needs. With so many new meds coming on the market, our options will expand.

Advances in medical therapy over the years have revolutionized the treatment of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis (UC). Biologics, which are medications made from living organisms rather than synthetic substances, have arguably made the biggest difference.

Prior to 1998, when Remicade (infliximab) was approved for Crohn’s disease, no biologics were available for IBD. A few other types of medications for IBD were available with variable efficacy prior to this, including steroids and some other oral medications, such as sulfasalazine, mesalamine, azathioprine, and 6-mercaptopurine. These medications did not work for everyone, and many people really suffered from their disease, often requiring multiple surgeries to manage it.

Now, with so many biologics available, many people with IBD are achieving full remission — they feel well, have few to no IBD symptoms, and do not show any evidence of inflammation when endoscopy is performed. Biologics have also helped people with IBD avoid invasive, often life-altering surgeries.

Now, excitement is building as even more biologics are on the horizon for IBD treatment. This will open more options to many people with IBD who are not achieving remission with the currently available biologics.

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Medications that block inflammatory molecules

White blood cells make a protein that can drive chronic intestinal inflammation. This protein is called interleukin 23, or IL-23 for short. Many medications already on the market target IL-23 to block this inflammatory reaction. One of these is the well-known Stelara (ustekinumab), which is FDA-approved for both Crohn’s disease and UC. (However, in addition to blocking IL-23, it also blocks interleukin-12, another inflammatory molecule.)

Skyrizi (risankizumab) is a newer biologic, built on the success of Stelara, that also targets IL-23. Skyrizi was initially approved for psoriasis and psoriatic arthritis, but it was FDA-approved for moderate to severe Crohn’s disease in June 2022. It’s now undergoing clinical trials for ulcerative colitis.

This medication is given initially as a series of three IV infusions, followed by at-home injections for maintenance. The most common side effects noted so far have been upper respiratory infections, headache, joint pain, injection site reactions, abdominal pain, anemia, fever, back pain, and urinary tract infections.

Most commercial insurance companies pay for this medication, though coverage varies by plan. AbbVie, the manufacturer of Skyrizi, has a payment assistance program that brings the cost of injections down to $5 per dose for people with commercial insurance. Those with Medicaid might pay as little as $20 or less per dose. But for people on Medicare with Part D alone (without supplemental insurance), this medication could cost over $900 per dose.

Other biologics on the horizon also target IL-23. One, called mirikizumab, has been shown to be effective for moderate to severe UC in clinical trials, and will likely be FDA-approved this year for UC. In fact, a recent phase 3 study showed that 50% of people who achieved remission after 12 weeks of taking “miri,” as it’s sometimes called, were still in clinical remission without the use of steroids after a year.

This promising med is also being investigated in clinical trials now for use in Crohn’s disease. The most common side effects seen in clinical trials for UC include upper respiratory infections, headache, anemia, cough, and nausea. Some trial participants also experienced worsening of UC, but this should not be alarming; it likely means it’s not the right medication for those people.

Another drug, known as guselkumab, is currently being studied in clinical trials for use in Crohn’s and UC. Studies are expected to be completed in October 2024 and July 2025, respectively. Common adverse effects include anemia, headache, upper respiratory tract infections, abdominal pain, and joint pain.

Medications that block white blood cells migrating to the GI tract

To cause inflammation in IBD, white blood cells must migrate to the gastrointestinal (GI) tract. There, they must fit, like a key into a lock, with a specific type of receptor, known as sphingosine-1-phosphate (or S1P) receptors. But if the receptor is blocked, it prevents some of these white blood cells from entering the GI tract and causing inflammation.

These medications, known as S1P receptor modulators, are not biologics, as they are not made from any living organism, and they are once-daily pills, in contrast to biologics, which are typically infusions or subcutaneous injections.

Zeposia (ozanimod) is the first S1P receptor modulator for IBD; it was FDA-approved for the treatment of moderate to severe ulcerative colitis in 2021. It’s currently being studied for the treatment of Crohn’s disease as well. However, this drug carries several safety considerations. Most notably, ozanimod is not safe for people with certain heart conditions, those with untreated sleep apnea, or those taking medications that are monoamine oxidase inhibitors.

With commercial insurance, ozanimod could cost you nothing. With Medicaid, ozanimod could cost $20 or less per month. However, with Medicare, coverage is variable.

Another S1P receptor modulator that is currently in clinical trials for the treatment of both Crohn’s and UC is called etrasimod. Side effects are similar to that of ozanimod. Etrasimod will likely be FDA-approved for the treatment of UC this year.

Medications that block white blood cells from adhering to the GI tract

In a complicated pathway, molecules called integrins enable cells to bind to each other and to other structural supports. In Crohn’s disease and UC, two particular integrins — α4β7 and α4β1 — are responsible for inflammatory white blood cells binding to tissues in the gut, causing inflammation.

By blocking these integrins, we can prevent inflammatory cells from increasing inflammation in the gut. Entyvio (vedolizumab) is one biologic that blocks the integrin α4β7 and is approved for both Crohn’s disease and ulcerative colitis. As of right now, vedolizumab is only available as an IV infusion for maintenance therapy. However, subcutaneous vedolizumab has been in the works for many years and may be FDA-approved this year.

Approval of a subcutaneous version would allow people to take injections at home rather than go to an infusion center for treatment.

A new medication, temporarily named AJM300 but set to be called Carogra (carotegrast methyl), was approved in Japan in March 2022 for people with moderately active UC who did not respond to other medications.

Carogra blocks both of the integrins involved in IBD. Carogra is a pill taken three times daily after meals. Major adverse effects could include upper respiratory infections, headache, and nausea. A clinical trial is expected to end by October 2023, and the FDA will likely review Carogra for approval in the United States. It’s also likely that the efficacy of Carogra with Crohn’s disease will be studied in the future.

Medications that block cell signaling pathways

Many cell signaling pathways in our bodies influence our immune system and the production of inflammatory molecules. One such pathway, known as the JAK-STAT pathway, is involved in the inflammatory processes of IBD. Xeljanz (tofacitinib) is one example of a JAK inhibitor, approved in pill form, to treat UC.

Rinvoq (upadacitinib) is a newer JAK inhibitor that was approved for the treatment of moderate to severe ulcerative colitis in March 2022. Rinvoq is currently undergoing clinical trials for use in Crohn’s disease.

Adverse effects of Rinvoq may include a higher risk of serious bacterial, fungal, or viral infections, shingles, higher risk of lymphoma or skin cancers, blood clots, and a higher risk of heart attacks or strokes — especially in those older than 50 who have pre-existing heart disease or risk factors like smoking, high cholesterol, and high blood pressure.

Updates to existing biologics

This year, we expect about eight new biosimilars for Humira (adalimumab) in the U.S. Biosimilars are biologic medications that are very similar to an existing medication, in this case Humira, but are produced by a different pharmaceutical company. Studies have shown biosimilars have the same efficacy and safety as the original medication, and biosimilars provide competition that drives down the cost of biologics.

Lastly, infliximab — the original biologic — is also undergoing FDA review for approval as a subcutaneous therapy (injection) in the U.S. Similar to vedolizumab, infliximab is currently available in the U.S. only as an IV infusion for maintenance therapy. However, during COVID, a subcutaneous biosimilar was used more frequently to reduce hospital visits. It turned out to be safe and equally effective to the original infliximab, and its use could become more widespread in the future.

The takeaway

In the end, more and more medications are being studied and becoming FDA-approved for use in Crohn’s disease and ulcerative colitis.

These medications offer promise, as people with difficult-to-control IBD often cycle through numerous medications before finding something that works. One of these medications could be the next step.