Immunomodulators for Moderate-Severe Ulcerative Colitis in Adults

If you live with ulcerative colitis (UC), common symptoms like belly pain, cramping, diarrhea, and blood in your stool can affect not only your day-to-day life, but your mental health, too. Having more than six bloody bowel movements a day is what doctors call moderate-to-severe UC. There’s no cure. But different treatments, like immunomodulators, can help you stay in remission.  

What Are Immunomodulators for UC?

Conventional, or nonbiologic, immunomodulators (IMs) are a type of disease-modifying antirheumatic drug (DMARD). IMs have been around since the 1960s. They’re a group of prescription drugs for certain autoimmune conditions, where an overactive immune system causes inflammation, pain, and other UC symptoms. Because they’re not biologics, they’re sometimes known as traditional DMARDs. 

These drugs can “turn down” your immune system. This is helpful since UC is caused, in large part, by an overactive immune system.  They can be helpful for some people with UC. But they can take up to 6 months to work and can cause side effects. Your doctor may have you try other treatments before trying immunomodulators. Or they may have you take an immunomodulator and a different type of medicine at the same time.

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Which Immunomodulators Are Prescribed to Treat UC?

Doctors have several different immunomodulator drugs they can prescribe to treat your UC symptoms:

How Do Immunomodulators Work?

Your immune system’s job is to defend you from foreign invaders, like viruses and bacteria, that could make you sick. But sometimes, this important defense system switches on and doesn’t turn off. Experts believe that’s what happens with UC. Your body keeps sending white blood cells into your colon and rectum to fight against an imagined enemy. The result is ongoing inflammation that causes sores in the lining of your large colon. 

Some IMs help by tamping down your immune system response. 

S1P receptor modulators seek out and attach themselves to a protein receptor called sphingosine 1-phosphate (S1P) on the surfaces of immune T and B cells. This stops the immune cells from being released in the blood.

When Are Immunomodulators Prescribed for UC?

IMs are treatments for moderate to severe UC. This means that your doctor will try other drugs before prescribing them. If your UC is mild to moderate, your doctor will likely first try to get your UC to remission with anti-inflammatory medications like:

5-aminosalicylates (5-ASAs). These drugs act specifically to reduce inflammation in your gut so it has a chance to heal. 

Corticosteroids. Because they can rapidly turn down your immune system response, these drugs are often prescribed when 5-ASAs don’t work well. But you don’t usually take them for a long period of time. A long course of steroids can raise your risk of health issues like glaucoma, cataracts, osteoporosis (thinning bones), increased infections, and high blood sugar.

If your UC is moderate to severe, your doctor may use biologics as your first-line treatment. Your doctor could prescribe an IM as the next step, either alone or along with a biologic.

Depending on the type they prescribe, you may get a course of steroids at the same time. The steroids can help you start to feel better right away, though you’ll need to take the IM for a few weeks or months before you see a difference.

You can also get IMs along with other treatments to help them work better. 

Your doctor could prescribe a biologic or an S1P receptor modulator if: 

  • Your symptoms don’t get better on a traditional DMARD
  • Traditional DMARDS cause serious side effects
  • You have moderate-to-severe UC

How Do You Take Immunomodulators for UC?

Each of these drugs comes with different guidelines:

Azathioprine (Azasan, Imuran)

This drug comes as a tablet that you take once or twice every 24 hours. You’ll need to swallow it at the same time each day. You can take azathioprine on an empty stomach or with food. 

Sometimes azathioprine can upset your stomach. If this happens, talk to your doctor. They may suggest that you take your dose right before bed or after a meal.

If you miss a dose of azathioprine, take it as soon as you remember. If it’s close to the next scheduled dose, call your pharmacist or doctor for advice.

6-mercaptopurine (Purinethol, Purixan)

Mercaptopurine comes in 50-milligram tablets that you take once a day or as a solution that you mix with a liquid and then drink. Like azathioprine, you should try to take it at the same time every day. You can take it on an empty stomach or with food, but you should always take it exactly the same way – with or without food – as you took your first dose. If you forget to take your dose, don’t take it once you remember. Skip that dose and take your next tablet at the scheduled time.

Cyclosporine A (Sandimmune, Neoral)

You could get this medication as capsules or a solution. You’ll probably take it twice a day at the same time. Your doctor will likely start you on a low dose, then adjust it to a larger dose over time.

Avoid grapefruit or grapefruit juice while you’re taking this drug. They can interfere with how your body absorbs tacrolimus. 

Tacrolimus (Prograf)

You could get this drug as a capsule that you take by mouth. 

If you take it by mouth, your doctor may advise you to take a dose every 12 hours so enough medication stays in your system. You’ll also need to take tacrolimus the same way each time. For instance, if you take it with food the first time, try to always take it with food. 

Grapefruit or grapefruit juice can interfere with how your body absorbs tacrolimus, so stay away from them while you’re taking it. 

S1P receptor modulators 

Etrasimod (Velsipity). You take this medication as a 2-milligram pill once a day, with or without food. Take the pill whole; don’t cut or crush it. Try to take it at the same time each day. If you miss a dose, don’t double up. Take your next dose at the scheduled time.

Ozanimod (Zeposia). For your first four days of treatment, take a 0.23-milligram capsule once per day. On days five to seven, take a 0.46-milligram capsule once per day. Starting on day eight, you’ll take a 0.92-milligram capsule once a day. When you get your prescription for this drug, you’ll get a starter pack with instructions for how to take it for the first week. 

Take the capsules whole, with or without food. 

It’s important not to miss a dose when you first start this medicine: If you miss a dose, you may need to restart the dosing series. After you’ve been taking this medicine for at least 2 weeks, if you miss a dose, skip the missed dose and take your next dose at the scheduled time.

How Effective Are Immunomodulators for UC?

Studies have shown that cyclosporine and tacrolimus work best when they’re used to get people currently having UC symptoms to remission. Azathioprine and 6-mercaptopurine are more effective at keeping people in remission and preventing relapse. 

Sphingosine 1-phosphate (S1P) receptor modulators

Etrasimod (Velsipity)

32% taking 2-milligram etrasimod achieved clinical remission by 52 weeks compared to 7% in placebo group

Ozanimod (Zeposia)

37% taking 1-milligram ozanimod achieved clinical remission by 52 weeks compared to 18.5% of placebo group

Are Immunomodulators Safe?

Like all drugs, IMs can cause side effects. 

Make sure to share any other medications, natural supplements, or recreational drugs you take and if you are pregnant, planning to have a baby or get someone else pregnant, or nursing. This information can help your doctor decide which IM is safest for you to take.

What Are the Common Side Effects of Immunomodulators for UC?

Every medication carries with it the chance of side effects. The ones you could have with immunomodulators for UC are:

Using azathioprine for a long time could also raise your risk for some types of cancers. Taking it is not advised if you’re pregnant or nursing.

Mercaptopurine can cause serious harm to a fetus. If you’re a woman or were assigned female at birth, it’s very important not to get pregnant while you’re taking mercaptopurine and for six months after you stop taking it. Use an effective form of birth control during this time. If you’re a man or were assigned male at birth, use an effective method of birth control while taking this drug and for three months after you stop. 

Taking this drug also raises your risk for more serious health issues such as diabetes, liver and kidney issues, and some types of cancer.

Some over-the-counter medications, vitamins, and herbal supplements, including ibuprofen and St. John’s wort, can interact with cyclosporine. Make sure your doctor knows what you take before you start this drug, and check with them first before trying anything new.

Because cyclosporine contains small amounts of alcohol, it may not be right for people who are pregnant, breastfeeding, or have conditions such as liver cirrhosis. Ask your doctor or pharmacist whether it’s safe for you to drink alcohol, drive a car, or operate machinery while you take this medication. 

Let your doctor know if you’re thinking about getting pregnant or nursing. Taking tacrolimus while pregnant could have harmful effects on your fetus.

No matter which IM you take, your doctor will want to keep a close eye on your health. They’ll regularly do tests to confirm that your organs are working well. 

Because IMs reduce the strength of your immune system, it will be important for you to let your doctor know if you start to feel sick. And while vaccines help keep you healthy, your doctor will need to advise you on the best timing and types to get.

How Much Do Immunomodulators Cost?

Depending on the medication you take, IMs for UC can be expensive. How much you’ll pay for your treatment depends on many different things, including what medication you’re taking, whether or not you have health insurance, the type of plan you have, and any other discounts you qualify for.

A couple of IMs are also included in drugmaker copay cards and coupons: 

VelsipityForMe. This copay savings program may help you get Velsipity at no cost if you have commercial insurance. 

Zeposia Support and Savings. If you have commercial insurance, this copay savings program can help you get your Zeposia prescription at no charge.

Clinical Trials for Immunomodulators

Clinical trials are a way to try new treatments before they’re available to the general public. These studies help to find new treatments and make sure they’re safe and effective. They may also show how existing treatments could work better. 

Ask your doctor if they know a clinical trial that might be a good fit for you. You can also search for “ulcerative colitis” at clinicaltrials.gov.

Are IMs Right for Me?

Treating UC isn’t a “one size fits all” approach. Your doctor and you will decide if you should try IMs based on a few factors.

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Cost. IMs have been shown to work well if you have moderate-to-severe ulcerative colitis. But it can be confusing to understand their cost. Contact your health plan to find out how much you’ll pay for a prescription. If you aren’t covered, contact a nonprofit like the Crohns and Colitis Foundation to see if you qualify for a patient assistance program. 

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Other medications you’ve tried. Before IMs, your doctor will probably first try to manage your mild to moderate symptoms with quick-acting medications that have fewer side effects, like steroids and 5-ASAs. For more severe UC, you’ll try biologics before immunomodulators. 

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Your health history. Your doctor will need to take into account any other health issues you live with, or may be at risk for. Because IMs reduce how well your immune system works, make sure you also understand the steps you’ll need to take to stay healthy. For instance, you’ll have to stay up to date on your vaccines, see your doctor more often, and have regular blood tests. Steer clear of exposure to germs as much as you can. Steer clear of exposure to germs as much as you can: Wash your hands regularly, stay away from people who are sick, and practice food safety when cooking and eating. 

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Potential side effects. Which side effects are you prepared to deal with to try to put your UC into remission? As with any new medication, make sure you’re aware of the possible risks. This is especially important if you’re thinking about starting a family. Some types of IMs can harm a developing fetus.

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Your lifestyle. Drugs, alcohol, and even over-the-counter supplements can interfere with how well IMs work for you and could cause more severe side effects. When talking about different treatment options with your doctor, be honest about any products you regularly use.

Show Sources

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