Best drugs to treat inflammatory bowel disease

Inflammatory bowel disease is a chronic condition that can cause diarrhea, pain, bleeding, anemia, intestinal blockage, and other serious problems. The two most common types of IBD are Crohn’s disease and ulcerative colitis, and may be treated with steroids and other medications. But if those don’t work or the side effects prove too bothersome, injectable medications called biologics are often used. Biologics don’t cure IBD, but they can alleviate symptoms and may reduce the chance of developing complications. 

Yet, the biologics can cause serious side effects such as fungal and bacterial infections, including tuberculosis, pneumonia, or staph, which rarely could be life-threatening. Minor side effects, such as pain and skin reactions where the drugs are injected, can also happen but usually do not require stopping or changing drugs.

Also, some of them are relatively new, so not much is known about their long-term safety.

There are six biologics approved by the Food and Drug Administration to treat IBD. Four—adalimumab (Humira), golimumab (Simponi), infliximab (Remicade), and vedolizumab (Entyvio)—are approved to treat ulcerative colitis, and five—Humira, certolizumab (Cimzia), Remicade, natalizumab (Tysabri), and Entyvio—are approved to treat Crohn’s disease. None of the drugs are available as a generic version, so they are all very expensive, ranging from $2,099 per month to more than $5,000 per month. Your out-of-pocket cost will probably be less if you have insurance. Due to the high price tag of biologics, your decision may come down to which biologic is covered by your drug plan.

Taking cost into account as well as effectiveness and safety, we have chosen the following as a Best Buy for people with Crohn’s disease or ulcerative colitis who have decided with their doctor that a biologic is appropriate:

• Adalimumab (Humira)

Humira is FDA-approved for treating both conditions. Studies show that Humira can help relieve symptoms by two weeks and can keep you in remission for one year. Humira has been in use for 12 years, so it has a longer track record compared to some of the newer biologics. It might also have a lower risk of side effects than some biologics, such as Remicade or Cimzia.

Some people don’t have good results with the first biologic they try. So if Humira doesn’t work for you, ask your doctor about your options. Your doctor might decide to try higher doses, administer the medication more often, or switch you to a different biologic.

About 1.4 million people in the U.S. have inflammatory bowel disease. The two most common types of IBD are Crohn’s disease and ulcerative colitis. Both cause inflammation in the lining of the intestines. Ulcerative colitis often causes bloody diarrhea and abdominal pain. Crohn’s disease and ulcerative colitis can cause weight loss, anemia, fever, malnutrition, joint pain, skin or eye problems, or mouth sores.

These conditions develop when the immune system turns against the body and attacks the intestines, causing inflammation, scarring, bleeding, and pain. Doctors don’t yet know what the immune system is attacking. One possibility is that the attack is misdirected at bacteria that live in the bowels and that are usually harmless in people who don’t have IBD.

Inflammatory bowel disease is often confused with irritable bowel syndrome, but these are two different conditions. IBS symptoms include abdominal pain, cramping, bloating, constipation, and diarrhea. While IBS can interfere with people's lives and cause them significant discomfort and distress, it does not cause the visible inflammation or permanent damage to the intestines that is associated with Crohn's disease and ulcerative colitis.

People may first develop IBD between the ages of 15 and 30 years old, but it can start at any time. Those with IBD have a normal life expectancy but they may suffer from symptoms for many years.

It’s not known what causes IBD, but modern-day living might play a role. IBD was rare before the 20th century. Today, in the U.S. and in Europe, Crohn’s disease and ulcerative colitis are more common in Northern regions. That pattern strongly indicates that environmental causes likely play a major role in the disorders. Other possible causes include smoking (Crohn’s disease only), low vitamin D levels, and oral contraceptive use. Intestinal infections and antibiotics may also play a role, possibly because they can change the type and number of bacteria that live in the body.

If you have symptoms of IBD, your doctor may conduct tests on your stools to check for infection. He or she might also draw blood to test for anemia, inflammation, and nutritional deficiencies, and take X-rays or other scans, including a CT or MRI. The doctor will probably perform a colonoscopy so that she can look at and take samples from the lining of the colon. But sometimes doctors might not be able to determine which condition a person has.

If you do have IBD, the type of medication your doctor prescribes will depend on the severity of your symptoms, how long you’ve had symptoms, and other medical problems you have.

People with “mild” IBD are usually treated with other medications before a biologic (See Table 1) such as corticosteroids, aminosalicylates, and antibiotics that will often induce remission. Other types of drugs called immunomodulators, such as azathioprine, mercaptopurine, and methotrexate might help maintain remission.

People with moderate to severe IBD—those who experience fever, weight loss, anemia, severe abdominal pain and tenderness, vomiting, or complications such as a perianal fistula or abscess— are often treated with intravenous steroids in a hospital, followed by an oral steroid such as prednisone.

But steroids don’t work in some people. Even when they do, they cannot be used for long periods of time to maintain remission because they can cause many serious complications, such as cataracts, high blood pressure, osteoporosis, thinning of the skin, type 2 diabetes, or weight gain. Another disadvantage of steroids is that they must be slowly decreased over time. Many people have flare-ups as they taper off, so the steroid dose then has to be increased again.

If steroids don’t work or a person is unable to taper off of the steroid, then a biologic is often used. Studies show that biologics can be effective for many people who haven’t responded to other medications, who have become dependent on steroids, or who have had or are at high risk of complications from steroids. We discuss biologics in more detail in the next section.

Table 1. Drugs for inflammatory bowel disease

Biologics work by suppressing the human body's immune system. This helps stop or reduce inflammation in the intestines and can help reduce other symptoms.

Because they interfere with the body’s protection against infection, biologics can be risky. But many other drugs used to treat IBD also interfere with the immune system and have serious risks. For some people, the main reason to switch to a biologic is to avoid the complications of corticosteroids, such as prednisone, which also suppress the immune system.

The six FDA-approved biologics we evaluated are:

All of the biologics are given by infusion or injection. As Table 2 shows, three of them—infliximab (Remicade), natalizumab (Tysabri), and vedolizumab (Entyvio)—are given through a vein in your arm (intravenously), while the others are injected under the skin (subcutaneously). Discuss with your doctor whether you feel comfortable injecting yourself or whether you prefer an intravenous infusion at your doctor’s office, hospital, or other outpatient center.

How often you have to take a biologic will depend on which drug you take. Humira, for example, is given every other week, while others are given once a month or every two months.

Table 2. Biologic drug dosing and delivery method

* Many of the biologics require several shots initially, followed by a maintenance period. The frequency listed in this table is the maintenance schedule.

Your doctor should not prescribe a biologic if you have an active infection. He or she might also decide not to prescribe a biologic if:

• You have had tuberculosis in the past that has not been treated.
• You have had other infections that were not treated.
• You have cancer.
• You have or had heart failure.
• You have certain neurologic disorders.

Some doctors recommend biologics before trying prednisone because of the risk of becoming “steroid dependent”—unable to stop prednisone without a flare-up in symptoms. But other doctors point out that not enough is known about the long-term benefits and side effects of starting out with a biologic.

It is the case that most studies of biologics have involved people who didn’t find relief with other medication, so we don’t know very much about the pros and cons of starting on a biologic before other medications. Biologics and prednisone provide quick relief, but biologics can be used for longer periods of time, whereas prednisone should only be used for short periods.

One strategy that doctors sometimes use is to have a patient begin using a biologic or prednisone for immediate relief and start azathioprine or mercaptopurine (both of which can take several months to work) at the same time to prevent recurrent symptoms. In studies, the combination of the biologic infliximab and azathioprine provided better clinical symptoms relief than either medication alone, although patients reported that their quality of life was similar with combination or single medication use.

Your choice of a biologic should take a number of factors into account, including the length of time the treatment is effective, risks of side effects, and your preferences regarding how the biologic is given, and how often. It’s good to know that how people respond to the drug can be different: some people experience a vast improvement in their symptoms and function, some see moderate changes, and others see little or no improvement at all.  

Cost is another important consideration. These drugs are very expensive, ranging in price from $2,099 per month to more than $5,000. For many people, insurance may not cover the full cost. Check with your insurance to figure out what your coverage will be, including the any charges related to administering the medication if you must go to a hospital or medical center to get it.

Which drug you begin with is important. If the first biologic you take works well and has minimal or tolerable side effects, it is generally not advisable to switch to another one because interrupting the scheduled treatments while the new biologic is taking effect increases the risk of a relapse.  

But if you do not do well on the first biologic you’re prescribed, your doctor might try a higher doses, give you the medication more often, or switch you to a different biologic. Higher and more frequent doses have not been adequately studied, though, and may not be approved by the Food and Drug Administration.

Those who have little or no improvement should try a different biologic or may need to consider other treatment options, such as surgery.

Table 3. Important considerations for selecting a biologic

There’s no clear indication that one biologic is more effective than the others. It’s also not known how biologics compare to each other in terms of effectiveness because no clinical studies have directly compared them. Instead, we must rely on studies that have compared each biologic to a placebo or to a combination of the biologic and another medication, but those results don’t allow us to reliably determine how the drugs might compare with each other.

It’s also impossible to predict how a particular person will respond. Some people experience a major improvement in their symptoms while others see no benefit.

Balancing the benefit and harm is particularly challenging because there’s a lack of long-term data on the safety of biologics from controlled trials. All biologics are currently being studied in large registries of patients that are intended to address long-term safety.

But serious problems can take years to show up. The two oldest biologics—infliximab (Remicade) and adalimumab (Humira)—have the most extensive evidence because they have in use the longest. Even for these, there is a lack of evidence for long-term safety at the higher doses and increased dosage frequency that are often used today. There are also fewer data for ulcerative colitis than for Crohn’s disease.

That said, here is what the available evidence shows about the biologics evaluated.

Ulcerative Colitis

Four biologics—adalimumab, golimumab, infliximab, and vedolizumab—are approved for treating moderate to severe ulcerative colitis. In clinical trials, about 35 percent of people with ulcerative colitis treated with infliximab achieved remission, compared with 15 percent to 30 percent of those who took a placebo. For adalimumab and golimumab, 16 to 19 percent achieved remission, versus about 10 percent of patients who took a placebo.

Beyond clinical trials, some patients achieve remission with more frequent dosing of infliximab than was used in the trials, so the rates of remission in practice might be better than has been seen in the studies.

The rates of people who remained in remission a year after they started a biologic ranged from 17 percent to 30 percent. People who took a biologic and achieved remission were about twice as likely to maintain the remission as those taking placebo. 

Several meta-analyses that looked at whether any of the four biologics for ulcerative colitis are more effective than the others have had conflicting results. Some indicated that infliximab may be more likely to induce a remission than adalimumab, but others found that all four are about equally effective.

The bottom line is that until a head-to-head trial is performed directly comparing biologics to each other, the choice of a biologic for ulcerative colitis should depend on the serious side effects it can cause, the chance of discontinuing the drug due to side effects, cost, and your preference regarding the route and frequency of treatment.

Crohn’s Disease

Biologics have been shown to help relieve Crohn’s disease symptoms and induce remission. In clinical trials, 26 percent to 57 percent of people who were treated with a biologic achieved remission, compared with 12 percent to 30 percent of those who received a placebo.

Five biologics are approved for Crohn’s disease—adalimumab, certolizumab, infliximab, natalizumab, and vedolizumab. Table 4 presents a summary of the evidence regarding how quickly the biologics work and whether a remission will last.

At two weeks after the first dose of a biologic, up to 47 percent of people were in remission compared with up to 30 percent of those who received placebo. According to network meta-analyses, among injectable biologics, adalimumab may be superior to certolizumab for inducing remission right away.

For people in remission, continuing a biologic helped maintain remission compared with those who took a placebo. With infliximab, adalimumab, certolizumab, and natalizumab, remission rates were 30 percent to 60 percent after 1 year of treatment compared with 12 percent to 44 percent among people who took a placebo.

It’s less clear if the remission is maintained at a year or more because many studies failed to report those results. Based on the limited data available, perhaps one in three people, or about 33 percent are still in remission at 1 year.

Table 4. Effectiveness of biologics for Crohn’s disease.

Age, race, and gender differences

People older than 65 and members of various ethnic groups have been underrepresented in most studies of biologics. Still, the existing evidence doesn’t indicate that any biologic evaluated in this report is more or less effective than the other biologics in older patients, people of any particular race or sex, or in patients who have other diseases. But some studies suggest that there are more complications in older people so your doctor may be less likely to prescribe a biologic in combination with another immunosuppressive medication if you are older.

A note about two other drugs: Tysabri and Entyvio

Tysabri has been associated with a serious brain infection called progressive multifocal leukoencephalopathy in about 1 per 1000 patients. This can cause severe disability or death. Because of this risk, Tysabri is available only through a special program called TOUCH. Only prescribers, infusion centers, and pharmacies registered with the program are allowed to prescribe, distribute, and infuse Tysabri.

In May 2014, the FDA approved a new biologic, Entyvio, for treating ulcerative colitis and Crohn’s disease. A recent meta-analysis indicates that Entyvio is as effective as other biologics for ulcerative colitis. But it might have a safety advantage because it works directly on the cells in the intestine. Other biologics suppress the immune system throughout the whole body, which is why they are associated with serious infections. But Entyvio works in a similar way as Tysabri, so the FDA was concerned whether Entyvio might also cause PML. So far, no patients taking Entyvio have developed PML.

The risk of experiencing side effects is an important factor to consider when choosing to take a biologic drug.

The mild side effects associated with these medications can include:

• Headache
• Skin reaction where the drug is injected
• Respiratory infection
• Urinary tract infection

Serious side effects can include:

• Allergic reactions
• Liver damage
• Cancer
• Serious infections: tuberculosis, pneumonia, staph, and certain fungal infections

Skin reactions where you are given the drug

For biologics that are injected under the skin (subcutaneously)—adalimumab, certolizumab (Cimzia), (Humira), and golimumab (Simponi)—people occasionally experience skin rashes, itching, and pain where the drug is injected. 

Infusion reactions

People also sometimes experience reactions to biologic drugs injected into a vein (infusion), such as infliximab (Remicade), natalizumab (Tysabri), and vedolizumab (Entyvio). These infusion reactions can include dizziness, chills, skin rashes, itching, headache, and fever. In less than 1 percent of people, these infusion reactions can be severe.

Infliximab has a higher risk of people discontinuing treatment due to side effects compared with adalimumab and golimumab. Infusion or allergic reactions contributed to the increased risk of discontinuation.

Infections

All of the biologics carry warnings on their labeling about serious infections. About three percent to four percent of people who take a biologic drug have an infection of some kind over the course of a year. Most of these are skin or lung infections including bronchitis or pneumonia. The additional risk of a serious infection from taking a biologic for up to two years is about 1 in 100. The risk of most serious infections is about the same or less than the risk from prednisone.

There are differences in the biologic drugs in the risk of certain infections they pose. For example, a British study found the relative risk of tuberculosis was three to four times higher for people who took adalimumab (Humira) and infliximab (Remicade) compared with another biologic etanercept (Enbrel). However, the rate of risk is a fairly low number—about one out of every 10,000 to 20,000 people who take a biologic.

If you have signs of an infection while taking a biologic, call or see your doctor right away. These include having the chills, a cough, diarrhea, feeling tired, a fever, muscle aches, and weight loss.

Cancer

All six of the biologics we evaluated have a warning on their drug label that they might increase the risk of certain cancers, including cancers of the breast and colon, lymphoma (a type of blood cancer), and certain types of skin cancers. In some cases, people have died from the cancer. 

But large, recent studies of people who took biologics for a variety of conditions have found no overall increased risk of developing cancers that can spread through the body (malignant), compared with people with the same diseases who did not take biologics.

Other side effects

People with serious congestive heart failure might worsen if they take a biologic. Some people develop a “lupus-like reaction” or signs of possible early multiple sclerosis. In almost all cases, these immune reactions disappear when the biologic is stopped.

Long-term risks of older biologics have not been identified. The first biologic—infliximab (Remicade)—has been on the market since 1998, and many experts think that long-term risks would have been detected by now. But for the newer drugs, serious problems can take 5 years or more to recognize, so there is not as much certainty about the long-term risks of those. The long-term risks of corticosteroids, in contrast, are quite serious and often affect multiple parts of the body.

Reducing risk

To reduce the risk of side effects, let your doctor know if you have:

• chronic obstructive pulmonary disease (COPD)
• congestive heart failure
• diabetes
• an infection or history of infections
• tuberculosis or a positive skin test for tuberculosis
• viral hepatitis
• multiple sclerosis

You must get a test for tuberculosis and hepatitis before you can start a biologic.

Also notify your doctor if you have been around a person with chicken pox, shingles, or tuberculosis, or if you are scheduled to receive a vaccine or have surgery.

The risk of biologics to unborn babies is unknown. Women of child-bearing age should use contraception while on biologics. Your doctor may ask you if you are thinking of becoming pregnant before you start a biologic. If you are planning to become pregnant, talk with your doctor about when to stop using contraception and biologics. The labeling of biologics advises these medications not be used by pregnant women unless necessary. If you do become pregnant while taking a biologic, your doctor may tell you to continue to take the biologic while monitoring you and your baby closely. Large international registries have not shown an increase in the risk of birth defects in women on biologic therapy.

Drug interactions

Biologics are often prescribed with additional drugs: azathioprine, mercaptopurine, or methotrexate. The chance of remission is higher with the combination than with a biologic alone. And the addition of one of those medications reduces the chance of developing antibodies to the biologic, and the chance of an infusion or injection-site reaction. But the long-term risks of combined therapy aren’t clear. There have been reports of people, particularly boys, who developed a rare, fatal cancer when using this combination of drugs, but little is known about how often this problem occurs or whether the duration of treatment affects the risk. The combination of a biologic with azathioprine or mercaptopurine was more common in cases of the fatal cancer, so methotrexate is often used in boys and men.

There is some evidence that when prednisone is taken with a biologic, the risk of fatal infection is higher than it is with taking just a biologic. So the goal is to taper off using prednisone as the biologic starts to work. Once you’ve stopped taking the prednisone, the risk of infection is lower.

You should not take two or more biologics in combination. Studies show that when more than one biologic is taken at the same time, there is a substantially higher rate of serious adverse events.

Because biologics affect your immune system, it’s recommended that you not be immunized with ‘live’ vaccines, such as the yellow fever vaccine or FluMist, while you are on biologic therapy. But in certain situations, a live vaccine may be necessary, for example, rubella immunization for women of childbearing age. Your doctor may recommend that you make sure to get all of your vaccines when you are treated for mild disease, before you take a biologic. Other vaccines, such as injected flu vaccines, are safe and can be administered with biologic medication. Discuss with your doctor any vaccines you plan to receive and read the package insert of the biologic you are taking—which can be found here.

We chose adalimumab (Humira) as a Best Buy for people who decide with their doctor that a biologic is appropriate for treating their Crohn’s disease or ulcerative colitis symptoms. This drug has been shown to start to relieve symptoms within two weeks and can keep you in remission for at least one year according to multiple trials.

Humira has been in use for 12 years so it has a longer track record than some of the newer biologics. Humira might have a lower risk of side effects compared to some biologics, such as Remicade and Cimzia.

People who are comfortable administering shots to themselves and do not want to travel to a hospital or medical center also might prefer Humira, which can be given as a self-administered injection at home.

As noted, insurance coverage might be an important factor. Check to find out what your plan covers and what your out-of-pocket costs will be. Adalimumab (Humira) costs nearly $3,200 per month depending on the dose if you paid the cost in full. You may also incur additional expenses, such as administration and office visit fees, so check with your insurance to find out how much you will have to pay out of pocket.

Many of the biologics manufacturers offer programs that provide the medication for free or for a small co-pay of $5 or $10 for a limited-time, such as 6 months or a year. Be sure to read the fine print. There are various criteria you must meet to qualify, such as having insurance. You’re likely not eligible if you use Medicare, Medicaid or any other federal insurance. These programs may also help provide discounted medication if you have a gap in your insurance coverage. You can find information about the programs by visiting the websites for the various medications or asking your doctor. The easiest way to find them is to do a Internet search for the brand name of the medication.

Our evaluation is based in part on an independent scientific review of the studies and research literature on therapies for Crohn’s disease conducted by a team of physicians and researchers at Johns Hopkins University Evidence-Based Practice Center. A synopsis of the EPC’s analysis of biologic drugs forms the basis for this report. A consultant to Consumer Reports Best Buy Drugs who has no financial interest in any pharmaceutical company or product prepared the synopsis. The full review of biologic drugs to treat Crohn’s disease is available here. (This is a long and technical document written for physicians and other medical researchers.)  The consultant also evaluated other independent, comprehensive systematic reviews and meta-analyses.

The monthly costs we cite were obtained from a health-care information company that tracks the sales of prescription drugs in the U.S. Prices for a drug can vary quite widely. All the prices in this report are national averages based on sales in retail outlets only. They reflect the cash price paid for a month’s supply of each drug in June 2014.

Consumer Reports selected the Best Buy Drugs using the following criteria. The drug had to:

· Be approved by the FDA to treat either Crohn’s disease or ulcerative colitis.

· Be as effective as other biologics (or more effective) when prescribed appropriately according to FDA guidelines, based on published randomized controlled trials.

· Have a safety record equal to or better than other biologics when prescribed appropriately.

The Consumers Reports Best Buy Drugs methodology is described in more detail in the Methods section at www.CRBestBuyDrugs.org.

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These materials are made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by the multistate settlement of consumer-fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).

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