The Latest and greatest treatments for IBD: What to believe
Dr. Stan Cohen is one of our founders and our CEO as well as the Chairman of our Medical Advisory Board. Dr.
What's the best IBD medicine for me? Confusion on television and in your inbox
By Dr. Stan Cohen
Reviewed by Dr. Jeffrey Hyams
Every time you turn on the TV, there's another (or maybe the same) commercial for a new medication, most for an auto-immune disease. Some of those are for Crohn's disease or ulcerative colitis or both. You may even wonder whether the ones being released for psoriasis or arthritis will be available for inflammatory bowel disease (IBD) soon. That's not unreasonable since some of the biologic medicines like infliximab, being used for IBD, started out treating another auto-immune disease until research showed it also was effective for one bowel disorder, and later research showed it could be used almost as effectively for the other.
What's amazing is that this explosion in medications just began about 30 years ago—while Crohn's disease itself was first described in 1932—almost a hundred years ago, with less effective medicines used for over half a century. Some are still in use today, for milder cases, or in combination with the newer medicines.
How these new medicines work in IBD
Inflammatory Bowel Disease (IBD) is a term that refers to two main conditions: Crohn's disease and ulcerative colitis. Both of these diseases are the result of chronic inflammation in the digestive tract. You can think of how a cut turns red and swollen as your immune system works to fight the possibility of an infection. That's inflammation. The difference is that acute inflammation is protective, goes away, then heals.
In IBD, the immune system mistakenly attacks the lining of the digestive tract, creating chronic inflammation and leading to symptoms like abdominal pain, diarrhea, fatigue, and weight loss.
The new treatments target specific molecules and the processes that produce the inflammation, by
- blocking certain proteins from becoming active
- stopping inflammatory cells from working
- interrupting the ways in the immune system over-reacts
they reduce inflammation, which
- helps the tissues heal
- maintains healthy tissues (remission)
- decreases symptoms and disease activity
- promotes a normal lifestyle
- lessens hospitalizations, surgeries, and cost
The medicines
The medicines described here have all been carefully tested for their safety and effectiveness, over years, in controlled clinical trials in adults before being released for use by the FDA in the United States and the similar agencies in Canada, Europe as well as countries around the globe. have been become an important option for many patients. They fall into two main categories:
- Biologics
- Small Molecules
What Are Biologic Medicines?
Biologic medicines, or biologics, are made from proteins, sugars, or cells using modern technology. Unlike traditional medications, which are often made from chemicals, or plants, biologics are more complex, and most often use DNA sources to create them. They were the first of the new medicines to be understood and tested, beginning in the 1980s, released almost 30 years ago and still in use today, because of their continued effectiveness and overall safety. Because biologics are complex in their structure and require careful administration, they are given through injections or infusions.
In the same way that generic medicines contain the same active ingredient as brand-name medicines though they may contain different (non-active) ingredients, several of the brand-name biologics have what are known as bio-similar drugs. These bio-similars are designed to be as safe, effective, and to have the same use as the original medicines, often called the originator or reference drug. But because both are made from living organisms, such as bacteria, yeast, or animal cells, the bio-similars aren't identical to the reference drug, and may be made in different ways and contain slightly different substances. They too have to be tested to be released by the FDA, though that testing is quite different. To date, only two medicines have expired patents, which is what allows their bio-similars to be marketed.
Types of Biologic Medicines for IBD
Anti-TNF Agents
Tumor Necrosis Factor (TNF) is a protein in the body that plays a role in inflammation. These medications work by binding to TNF, preventing it from attaching to its receptors on immune cells. This helps stop the inflammatory process that causes the symptoms of IBD. The ones used in the US:
- Infliximab (Remicade is the originator drug) helps both Crohn's disease and ulcerative colitis. It is given through an IV, every 4-8 weeks in a maintenance program after the first 3 "induction" infusions to get it established, with blood tests and each person's response guiding the dose and the frequency it is given.
- Adalimumab (Humira is the originator drug) also helps both Crohn's disease and ulcerative colitis. It is an injection (a shot) into the tissues under the skin, usually given every other week. Blood tests and each person's response guides the frequency it is given. The shot's dose stays the same.
- Certolizumab (Cimzia) is used in Crohn's disease is given with a loading dose of 2 injections every 2 weeks for 3 injections, then every 4 weeks. It does not cross the placenta tissues and is recommended for many pregnancies
- Golimumab (Simponi) is used in ulcerative colitis as another injection (a shot) into the tissues under the skin, but it only needs to be given every 4 weeks. Dosing and frequency do not often change.
Possible anti-TNF Side effects
Like all medicines, anti-TNF agents may cause side effects. Side effects might include:
- Increased risk of infections: Because these medicines suppress the immune system, patients may be more likely to get sick.
- Injection site reactions: Patients may experience pain, swelling, or redness where the injection (shot) is given.
- Allergic reactions: can occur with both the IV and shots, but the reactions to the IV can be dramatic, and can usually be controlled with medication and stopping the infusion.
- Headaches
- Nausea
- Much rarer side effects, increased risk of cancer or neurological conditions
Integrin Inhibitors
Integrins are proteins that help white blood cells move into the gut. By binding to these proteins, integrin inhibitors prevent their movement and the inflammation that follows. The only one in use now for IBD is
- Vedolizumab (Entyvio) is given through an IV and targets the gut specifically, which may result in fewer side effects than other integrin inhibitors that have an effect in other areas.
Possible side effects of Integrin inhibitors
The main potential side effects of integrin inhibitors include:
- Headaches
- Nausea.
- Fatigue.
- Rarely, increased risk of infections, although generally lower than with anti-TNF agents.
Interleukin-23 (IL-23) Blockers
Interleukins are other proteins involved in the body's response to injury or infection. IL-23, and to a smaller extent IL-12, activate certain immune cells called T-helper 17 (Th17) cells, which produce more inflammatory substances.
When IL-23 is overactive, it can lead to excessive inflammation, contributing to the symptoms of Crohn's disease. Because of its role in the disease, researchers have focused on developing treatments that target IL-23 to help reduce inflammation and improve symptoms.
Types of IL-23 inhibitors
Several IL-23 inhibitors are currently used for Crohn's disease and / or ulcerative colitis. They are also used for other auto-immune conditions, but with different dosing. Of note, some interleukin inhibitors are approved for those other conditions, but are not used for IBD. The ones used in the US, with a flurry of commercials and advertisements are:
Ustekinumab (Stelara) has been available longest of this group and is used for the treatment of Crohn's disease. Ustekinumab binds to both IL-12 and IL-23, blocking their action on immune cells and inflammation. After an initial loading injection based on a person's weight, the shots are then given by injections that are at a standard maintenance dose, usually every 8 weeks.
Risankizumab (Skyrizi) blocks IL-23's effects in both Crohn's disease and ulcerative colitis. It is given with 3 loading doses by IV (with a higher dose for ulcerative colitis) and then shots every 8 weeks.
Guselkumab (Tremfiya) also blocks IL-23, and has been approved for ulcerative colitis. Three (3) IV loading doses are given. Then, depending on a person's response, the injections are given either every 4 or 8 weeks.
Mirikizumab (Omvoh) is an IL-23 inhibitor that is also approved for ulcerative colitis, and currently being studied for its effectiveness in treating Crohn's disease. The first 3 IV induction doses are followed by 2 injections every 4 weeks.
Possible side effects of IL-23 inhibitors
Because these are similar medications, all targeting the interleukins, their possible side effects are basically the same, including:
- Risk of infections, though less than the anti-TNF medicines
- Allergic reactions
- Headaches
- Fatigue
Types of small molecules to treat IBD
JAK Inhibitors
Janus kinase (JAK) enzymes are involved in the signaling pathways that lead to inflammation. By blocking these pathways, the medicine can reduce inflammation and alleviate symptoms. They are not considered firsts line drugs and their current indication is after an anti-TNF fails. Theymay be effective when another potent IBD medication doesn't work or can't be tolerated.
Tofacitinib (Xeljanz) is a pill that is often effective for moderate to severe ulcerative colitis when an anti-TNF medicine did not work or couldn't be tolerated.
Upadacitanib (Rinvoq) is a pill indicated for those with moderate or severe Crohn's disease who did not respond to the anti-TNF medicines discussed above.
Possible Side Effects of JAK inhibitors
While JAK inhibitors can be effective, they may have possible side effects, including:
- Serious infections: Similar to other immunosuppressive medications.
- Elevated liver enzymes: This can indicate liver issues.
- Blood clots: There is a potential risk for clots, especially in people with other risk factors.
- Heart attack or stroke for older adults who also have other risk factors for heart disease
S1P Receptor Modulators
Sphingosine-1-phosphate (S1P) is a molecule helps regulate immune cell movement. By targeting S1P receptors, these medications can help to control how immune cells travel through the body. This can help prevent these cells from entering the intestine and causing inflammation.
Ozanimod (Zeposia) is a pill for ulcerative colitis that is gradually increased over the first seven days until it reaches its full dose. An EKG should be taken before starting, along with the usual blood tests.
Etrasimod (Velsipity), is once a day pill for ulcerative colitis that is maintained at the same dose from the start of treatment. An EKG should be taken before starting, along with the usual blood tests.
Possible Side Effects of S1P modulators
S1P receptor modulators can have side effects, including:
- Increased risk of infections: Similar to other immunosuppressive drugs.
- Liver function changes: Regular blood tests may be needed to monitor liver health.
- Bradycardia: This is a condition where the heart beats more slowly than normal, which can lead to dizziness or fainting.
Which is the right medicine for you?
Several factors determine which is the best medicine to try first. Notice I said "try." Some medicines work better for some people than others. I also said "first," which means that these new medicines offer great options, and that there are usually others if that first one isn't effective or causes side effects that are significant problems—but remember the benefits generally outweigh the risk. Remember too, the goal of treatment is to achieve a healed intestine and to maintain remission, allowing patients to lead normal, healthy lives.
Factors
- The severity of the disease: More severe cases may require stronger treatments.
- Your medical history: You may have had allergies or reactions to certain medicines, or a condition that disqualifies you from a medication.
- Your preference: You may prefer injections over infusions or pills.
- Insurance: Unfortunately, insurance companies and cost or availability may dictate what medicine you can take.
- Clinical trials: Scientists and doctors are always looking for new ways to improve treatments and find better medicines with fewer side effects. Sometimes, promising medicines that aren't available yet can be obtained so you can participate if other medicines aren't working for you
Conclusion
The new, targeted medicines are changing how IBD is treated. Since everyone's IBD is different, we're entering a time when your treatment can be personalized for you. All of them work on specific parts of the immune system, help reduce inflammation and improve quality of life for many patients. While they have potential side effects, the benefits often outweigh the risk, blood tests and other procedures will also help to monitor their benefit and for side effects.
Also know that medicines are only one part of the what you can do for yourself. Diet, exercise and attitude / good mental health are also important to help how you feel.
One last important point. Only Remicade and Humira, and their biosimilars, are approved by the FDA for people <18 years of age. But, because pediatric and adult IBD are thought to have similar mechanisms controlling inflammation, pediatric doctors use other medications "off-label". This does not mean unsafe. It just means that these doctors are trying to find the best medicines for their patients. It is also common that many insurance companies try to block this use, so doctors need to get pre-authorization, or an okay to use. This process can be long and complicated.
References
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This article, as well as all others, was reviewed and edited by a member of our Medical Advisory Board.
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