Medically reviewed by Jonathan Hansen, MD, PhD
Biologic medicines are different from more traditional oral medications because they are large, complex molecules that must be delivered by injection. Using a biologic medicine to treat your IBD may seem a bit like offering your body up as a science experiment, but fortunately that isn’t the case. Biologics are great because they are natural proteins that target specific pathways in the body more accurately than traditional oral medications. In fact, they can be quite wonderful for those 40% or so of patients that find biologics effective in maintaining long-term remission.
However, these drugs can stop working in some individuals because their bodies develop an anti-drug immune response to them over time. This means that their body may suddenly decide not to accept this treatment and essentially start fighting to remove it, in much the same way their body might fight off a virus or infection. This immune response is more likely to occur if patients take a so-called “drug holiday,” where they stop taking the medicine for any number of reasons. When they resume the medicine, they might find that the biologic no longer works. Because of this risk, their doctor will likely recommend that they continue to take it as long as it is working and not causing any side effects. Sometime biologics are combined with immune system suppressors to help prevent the formation of anti-drug immune responses and prolong the effectiveness of biologics.
Currently, there are three different classes of biologic medicines used to treat IBD: anti-TNF, anti-integrin and anti-IL-12p40 medicines. In general, they are relatively safe for long-term use. Some people see an improvement in their IBD symptoms soon after starting these drugs, while others may need to take them for several months` to determine if they are effective.
Let’s take a look at each class and the unique features of them:
Anti-TNF agents bind and block tumor necrosis factor, a small protein that causes inflammation, including that found during IBD. This biologic class not only reduces inflammation in the gut, it also promotes healing of the intestine. Of the biologics, they have been around the longest and are the most widely prescribed for IBD. They are approved for Crohn’s disease and ulcerative colitis and are often the first biologic a doctor will prescribe for IBD since they are probably the most effective of the currently-available biologics.
Common anti-TNFs prescribed for IBD include: adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi), which are all available as a skin injection that can be taken at home much like an insulin shot. Infliximab (Remicade) and infliximab-dyyb (Inflectra) are anti-TNFs given as an IV infusion over two to four hours, most often in a doctor’s office. Usually, the first few doses are given either at a higher dosage or closer together to help the medication quickly build up in the body, then dosing is repeated every two to eight weeks thereafter depending on the specific anti-TNF. About half of people who take an anti-TNF will find they need to switch to a different one, or to a different biologic altogether, over the course of five years of treatment in order to maintain remission.
An important, though rare, side-effect of anti-TNFs is an increased risk of infection, including acquiring or reactivating some rare infections such as tuberculosis and chronic hepatitis B, so a doctor will want to test for these conditions before starting a patient on these medicines. People receiving anti-TNFs can do their part to prevent infections by staying up-to-date on recommended vaccinations, including those for pneumonia and influenza. Anti-TNFs have also been associated with a slightly increased risk of lymphoma, a type of blood cancer. This risk is slightly higher in older IBD patients, as well as in those who are on a combination therapy with an immune system suppressing drug.
Sometimes taking an anti-TNF causes the patient to develop a skin rash called psoriasis, or problems with the nerves, heart or liver. However, the likelihood that people develop any of these side-effects to anti-TNFs is very small and the benefits of taking them often outweigh these risks. Individuals should discuss the pros and cons of taking these medications with their doctor before starting.
Anti-integrins treat IBD by preventing the cells that cause inflammation from moving out of the blood vessels and into the intestine tissue. They do this by blocking proteins on the cell’s surface that target the cells to the inflamed intestine. Anti-integrins that are prescribed for IBD include: vedolizumab (Entyvio) and natalizumab (Tysabri).
Natalizumab is only approved for Crohn’s disease, but has fallen out of favor because it is associated with a small risk of a serious brain infection called progressive multifocal leukoencephalopathy. Vedolizumab on the other hand is designed to eliminate the risk of the serious brain infection and is approved for ulcerative colitis and Crohn’s, though it appears to be more effective for ulcerative colitis than Crohn’s. Both are administered via an IV infusion at a doctor’s office much like infliximab and are repeated every four to eight weeks depending on the agent. Side effects to vedolizumab are very rare, but might include upper respiratory tract infections
The newest of the biologics that is approved to treat IBD is ustekinumab (Stelara®). It blocks IL-12p40, a small protein in the body that contributes to the inflammation in IBD. It is currently only approved for Crohn’s disease and a skin condition called psoriasis. It is considered relatively safe, but similar to anti-TNFs, has a very low risk of causing reactivation of tuberculosis in those who have been exposed to tuberculosis in the past. Ustekinumab is generally used in Crohn’s patients that do not respond to, or cannot tolerate, anti-TNFs However, a study of 741 Crohn’s patients who had previously failed anti-TNFs showed that only 34% of patients responded to ustekinumab vs. 22% of patients given placebo. Therefore, there is still a lot of room for improvement in treating Crohn’s patients who have failed anti-TNFs.
What to Ask Your Doctor
Before starting biologics, patients should discuss with their doctor the relative benefits and risks of each treatment option, the potential expense of biologics, side effects to watch out for, and the need for pre-treatment testing for certain infections. Biologics are only effective for less than half of IBD patients in the long-run. Still, they are worth trying and are among the most effective medications currently available to treat IBD.
Medical reviewer and Oshi physician-partner Jonathan Hansen, MD, PhD, has been involved in 20-plus clinical trials of investigational compounds that target various pathways important in the development of IBD. He has co-authored book chapters on IBD and been published in a variety of peer-reviewed journals, and his interests include the role of environmental bacteria in the development of chronic intestinal inflammation. Dr. Hansen serves as an Associate Professor of Medicine in the Division of Gastroenterology & Hepatology at the University of North Carolina at Chapel Hill. He received his BS in Biochemistry from Brigham Young University, and his MD and PhD in Microbiology and Immunology from Indiana University School of Medicine.
Oshi is a tracking tool and content resource. It does not render medical advice or services, and it is not intended to diagnose, treat, cure, or prevent any disease. You should always review this information with your healthcare professionals.