When a patient with Crohn’s disease or ulcerative colitis makes plans, there’s always an “if factor.” I’ll come to the party if my stomach doesn't hurt too much. We’ll be at the big game if I'm not fatigued or tethered to the bathroom.
Effective therapeutic antibody drugs for these two main forms of inflammatory bowel disease (IBD) have been available since the late 1990s. But they remained few in number, limiting patients’ options, both when making an initial treatment choice and when needing to move to another therapy.
Today, three new classes of medication offer targeted inflammation control. Interleukin-23 (IL-23) selective inhibitors, sphingosine 1-phosphate (S1P) modulators, and Janus kinase inhibitors (JAKi) interfere with the function of specific inflammation-inducing proteins in patients with Crohn’s disease and ulcerative colitis.
UT Southwestern led two research reviews, published in 2025 in Current Gastroenterology Reports and Clinical Gastroenterology and Hepatology, that summarize the safety and effectiveness of these new drugs. Data showed that each drug can be safe and effective for IBD, either as a first-line treatment or, in most cases, after a past medication has failed.
The key is to choose the right medication based on a patient’s individual health needs, risk factors, and preferences. Our goal is to get you back to the quality of life you previously enjoyed – feeling so well that routine monitoring with your doctor becomes just another visit, not a dreaded appointment.
These three new medication classes can help more people with IBD break free from the “if factor” and achieve sustainable remission.
What is IBD?
Inflammatory bowel disease is a chronic inflammatory condition of the gut. Two of the most common types are Crohn's disease, which can affect any part of the gastrointestinal tract, and ulcerative colitis, which affects only the colon.
A combination of genetic and environmental factors contributes to IBD, which can cause persistent abdominal pain, diarrhea, fatigue, and unintended weight loss. Patients with IBD can be at an increased risk of colorectal cancer due to chronic inflammation.
There is not yet a cure for Crohn's disease, though IBD surgery can remove the inflammation in some cases of ulcerative colitis. Medication is typically the most effective treatment to control the life-disrupting symptoms of either disease.
Patients used to start treatment with an anti-tumor necrosis factor (TNF) agent, which targets the TNF protein. TNF helps grow new cells and eliminate old ones, but it can cause inflammation when found in excess. Today, the first line of care is shifting toward three new medication classes.
How targeted IBD medications work
All therapeutic antibody medications (biologics) and advanced small molecules reduce inflammation. The new classes target specific inflammation drivers to control IBD symptoms. Each type can help patients achieve clinical remission (significant reduction or resolution of symptoms), endoscopic remission (no visible inflammation in the gastrointestinal tract), or both depending on their condition and health history.
Interleukin-23 selective inhibitors
IL-23 selective inhibitors, such as risankizumab, guselkumab, and mirikizumab, block the action of the pro-inflammatory cytokine interleukin-23. Cytokines are proteins that help activate or suppress the immune system’s inflammation response. Targeting just IL-23 means normal, healthy inflammation can continue, resulting in fewer side effects.
Head-to-head data and clinical trial outcomes show the effectiveness of IL-23 selective agents on moderate to severe IBD:
- Risankizumab put twice as many patients with Crohn’s disease into endoscopic remission within 48 weeks compared to ustekinumab (32% versus 16%). These patients had previously tried anti-TNF therapy.
- Risankizumab brought more than three times as many patients with ulcerative colitis into remission within 12 weeks compared with a placebo (21% versus 6%), regardless of past anti-TNF drug exposure.
- Mirikizumab offers similar outcomes to ustekinumab for Crohn’s disease, regardless of prior biologic drug response.
- For ulcerative colitis, mirikizumab put over half of patients in the LUCENT-1 and LUCENT-2 clinical trials into clinical remission within 52 weeks compared with a placebo.
- Guselkumab is the first IL-23 inhibitor that offers an option for the first doses to be given as an injection under the skin rather than delivered intravenously during an infusion visit, prior to transitioning to longer-term subcutaneous dosing. That could benefit some patients. GALAXI clinical trial results showed guselkumab to be superior to ustekinumab in the number of patients achieving clinical remission as well as those who achieved clinical remission and endoscopic response after 48 weeks.
Sphingosine 1-phosphate modulators
S1P modulators, including ozanimod and etrasimod, target specific proteins linked to inflammation on immune cells and stop them from leaving the lymph nodes – a network of glands that filter out germs and immune system waste.
Clinical trial data for moderate to severe ulcerative colitis showed that:
- Ozanimod resulted in three times the remissions (18% versus 6%) and nearly double the clinical response (48% versus 26%) compared with a placebo within 10 weeks.
- Etrasimod delivered more than four times the clinical remission rate (32% versus 7%) and triple the endoscopic improvement (39% versus 13%) compared with the placebo within 52 weeks.
Janus kinase inhibitors
JAK inhibitors, such as tofacitinib and upadacitinib, stop several types of pro-inflammatory cytokines from forming.
[DF1] JAK inhibitors might be the most effective medicines for ulcerative colitis. Tofacitinib performs better than ustekinumab in patients who’ve tried anti-TNF [MT2] agents. Tofacitinib also produced better results than vedolizumab[MT3] , a drug that blocks the α4β7 integrin protein that shepherds immune cells throughout the body.
Upadacitinib was developed as a rheumatoid arthritis [MT4] medication and was subsequently found to be effective in both ulcerative colitis and Crohn’s. Research has shown that more than 80% [MT5] of participants with ulcerative colitis who have tried an anti-TNF drug got a clinical response or remission within eight weeks when using upadacitinib. In another study involving patients with Crohn’s disease who did not respond to anti-TNF drugs, vedolizumab, or ustekinumab, nearly 64[MT6] % got a clinical response with upadacitinib, and another 27% went into remission within three months.
JAKi are not as precise as the other two new drug classes. In specific populations, they can increase the risk of specific adverse side effects. For example, in patients 65 and older with rheumatoid arthritis and a history of smoking, JAK inhibitor use is associated with higher rates of cardiovascular events and cancer compared with anti-TNF agents. While we have not seen this trend in patients with IBD, JAK inhibitors should be considered in the context of all of a patient’s health conditions.
Related reading: Frequently asked questions about IBD
3 questions to ask a doctor about IBD medications
In general, the most effective IBD treatment will both reduce your symptoms and minimize the risk of adverse side effects. The best IBD drug for you will be based on your condition, symptoms, and overall health.
Ask your doctor these three questions when you’re discussing a new drug recommendation or medication changes.
How do I take the drug?
IBD drugs can come as oral pills, injections, IV infusions, or a combination of methods. You’ll want to be comfortable taking your medication as prescribed. Talk with a doctor about your options and ask for guidance in how and when to take the drug if you are unsure.
Why did you recommend this medication for me?
While the new, targeted drugs are shown to be safe and effective for IBD, each person should understand the benefits and possible side effects based on their own health history. Ask the doctor if there is any concern about adverse reactions and why their recommendation is the best choice for you.
Will this treatment affect my other health conditions?
It’s possible to have more than one autoimmune disease. Patients with IBD may also have psoriasis, rheumatoid arthritis, or ankylosing spondylitis. For many patients, it is easier to take one medication that will treat both conditions. If you have more than one autoimmune disease, work with your doctor to understand how a new treatment recommendation may affect your overall health and symptoms.
In the next five years, we expect to see expanded forms of the new IBD medications. Drugs that currently come only as infusions likely will become available as injections or pills, giving patients more choices to customize their care.
One goal is for all patients to escape the “if factor.” You deserve to live in the moment and keep the plans you make. Reclaiming that freedom starts with a customized IBD treatment plan. Let us help you find a safe, reliable solution for Crohn’s disease or ulcerative colitis.
To talk with an expert about IBD treatment options, make an appointment by calling 214-645-0595 or request an appointment online.
