Weighing the new approaches to treating Crohn's and ulcerative colitis

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a condition that involves inflammation of the digestive tract. In recent years, treatment options for IBD have rapidly expanded. The goal of these newer treatments is to improve control of inflammation in the gut, which can greatly improve patients' quality of life.

Medication options for IBD

5-aminosalicylates: This class of drugs contain 5-aminosalicylic acid, which works to reduce inflammation in the intestine. Sulfasalazine and mesalamine (available in oral and rectal forms) are often prescribed for patients with mild UC or CD of the colon, but are especially helpful in patients with inflammation limited to the rectum and sigmoid colon. Aminosalicylates are generally well tolerated, but it is important for blood tests (including those for kidney function) to be monitored closely every few months while taking the medication.

Biologics: These medications target specific proteins and pathways to reduce inflammation in IBD. Biologics, which historically were reserved for severe cases, are now often a first-line approach for patients with CD and UC. This class of medications is a rapidly developing area of research, with several ongoing clinical trials and newly-approved agents.

• Anti-TNF alpha therapies: These medications block a protein called tumor necrosis factor (TNF) to reduce inflammation, and are used in both CD and UC patients. Infliximab and adalimumab are some examples of anti-TNF drugs. With anti-TNF alpha therapies, you will require frequent blood tests to follow your response to treatment. Additionally, an approach called therapeutic drug monitoring, where drug concentrations in the blood are measured, can be used to tailor the dosage of medication to an individual patient's needs.
• Anti-IL-12/23: These therapies reduce intestinal inflammation by inhibiting specific pro-inflammatory proteins called interleukin-12 and interleukin-23. Ustekinumab is FDA-approved to treat both UC and CD. Risankizumab was FDA-approved in June 2022 to treat moderate to severe CD; clinical trials to assess its utility in UC are ongoing.
• Anti-Integrin: These medications block white blood cells that cause inflammation from entering the GI tract. Vedolizumab has been shown to be an effective treatment that is tolerated well in IBD patients. Natalizumab has been approved to treat moderate to severe CD, but is less commonly used due to its side effect profile.

Small molecules: This newer class of medications uses molecules that are small enough to easily enter cells in order to modify different inflammatory pathways in the body. One advantage to these treatments is that they are orally administered, and therefore may be more convenient for patients.

• JAK inhibitors: These therapies interfere with the activity of Janus kinases (JAK), which normally work to stimulate the body's inflammatory response. Tofacitinib has been approved for the treatment of moderate to severe UC, and is being investigated in CD. Upadacitinib was shown to have high clinical remission rate in UC, and was FDA-approved in March of 2022.
• S1P receptor modulators: This class of medication blocks the receptor of a signaling fat molecule called S1P, in order to reduce inflammation and the immune response. Ozanimod was approved in May of 2021 for the treatment of moderate to severe UC.

Corticosteroids: The use of oral corticosteroids such as prednisone was once a mainstay of IBD treatment, but now is typically reserved for short-term usage for patients with active flare symptoms. These medications are associated with increased risk of infection, blood clots, bone thinning, and hyperglycemia, among other unfavorable side effects. One specific type of oral corticosteroid called budesonide is primarily released in the gastrointestinal tract, and is associated with fewer adverse effects.

Immunomodulators: These medications reduce inflammation in the gastrointestinal tract by suppressing the immune system, and can be effective in treating both CD and UC. Azathioprine, methotrexate, 6-mercaptopurine, tacrolimus, and cyclosporin are some examples. However, their usage as a primary treatment is declining due to adverse side effects such as bone marrow suppression, increased risk for certain blood cancers, liver injury, and gastrointestinal intolerance.

Sometimes, these medications are used in lower doses in combination with biologic medications in order to optimize the effectiveness of treatment and prevent the development of antidrug antibodies to biologics. Patients on these medications require regular blood tests for monitoring.

Which treatment is right for me?

IBD treatment plans are complex, and are personalized for each patient. Your past medical history, disease severity and location, type of IBD, and response to past treatments are some of the many factors in deciding which medication is right for you.

To assess your treatment, your doctor will continue to use a combination of your symptoms, blood work, stool tests, imaging, and endoscopy (upper endoscopy and/or colonoscopy) to determine if your treatment is working or needs adjustments. Sometimes this means changing the dosage or frequency of your current medication, adding a second medication, or starting you on a different type of treatment. The goal is to find the right medications for you for the long term, and to achieve clinical remission.

What happens if I cannot afford my recommended treatment?

There are several options to reduce the cost of IBD treatments. Your doctor can work with you to see if the drug manufacturer offers patient financial assistance programs that provide medication at a discounted cost. Additionally, your doctor may work with your insurance company to prescribe more affordable biosimilars (medicines with similar structure, function, and clinical efficacy as standard biologic drugs).

In some cases, missing doses of medication may lead to the development of antidrug antibodies, which can make a patient vulnerable to serious allergic reactions when the medication is restarted. Additionally, medication gaps can make patients with IBD more susceptible to flares and complications, including surgery and hospitalization. For these reasons, it is important to work with your doctor, insurance company, and the manufacturer of any medication you are on to minimize gaps in medication dosing.

Crohn's and ulcerative colitis are lifelong, chronic conditions. However, when remission is achieved, most people have an excellent quality of life. Additionally, every patient's symptom course is unique. If you are concerned about medication costs or safety, or are considering stopping your medications, reach out to your doctor to discuss a personalized solution for you.