Advances in the Treatment of Crohn’s Disease

By Dr. Peter Higgins

Treating patients with Crohn’s disease has changed a lot over the past decades thanks to recent advances in medical research. Here is what you need to know about the most up-to-date treatment strategies.

Goals of Treatment

In the past, treatment for Crohn’s disease was considered successful if there was an improvement in a patient’s symptoms (such as diarrhea, abdominal pain, sleep and energy problems). Though it is important for patients to feel better with medical therapy, current research has shown that it is the inflammation in the bowel which eventually causes the most significant complications of this disease. Complications like cancer, fistulas, an abscesses are the result of a smoldering inflammation that goes untreated. Therefore, physicians will treat your Crohn’s with the intent of reducing inflammation. How will they know if the treatment is working? Your doctor may send you for tests. Objective measures such as fecal calprotectin (a stool test that measures inflammation in the bowel), CRP (a blood test for inflammation), colonoscopy, and CT scan will help determine if the inflammation is controlled.

Newer Medications

Forty years ago, Crohn’s disease was treated with prednisone, a steroid, because it made patients feel better quickly. Over time, patients found that it was less effective the more frequently they used it. It also did not prevent complications caused by Crohn’s that resulted in the need for surgery. To help treat Crohn’s without using steroids, a class of drugs called immunomodulators (IMM) began being used. Immunomodulators such as azathioprine and 6 mercaptopurine helped some patients achieve long-term remission of their illness. However, up to 70% of patients were still experiencing the effects of their Crohn’s disease despite the use of IMM and steroids.

The development of a class of drugs known as biologics was a major advancement in the treatment of inflammatory bowel disease. In 1998, Remicade was the first medication in the class of biologics to be established for Crohn’s disease and other immune-mediated diseases. Remicade works by blocking a protein in your body called tumor necrosis factor (TNF) before it can activate white blood cells to cause inflammation in your bowel. Other medications in the same family, such as Humira, Cimzia, and Simponi, work in a similar way and are available on the market today. These drugs work to reduce inflammation and prevent complications. They are also more effective at helping control Crohn’s disease than previous medications such as IMM. Half of patients taking a biologic therapy achieve remission of symptoms compared to only one-third with an IMM. Like all medications, biologics can have side effects and it is important to be aware of them. However, for many patients, the benefits of taking this class of medication outweigh the risks.

Newer research has shown that taking a biologic medication with an IMM helps patients benefit from the biologic for a longer period of time. This is because research found that many patients lost their positive response to biologics over time. Investigations found that in some cases, elements of the body’s own immune system, called antibodies, react to the biologic medication and cause it to be cleared from the body faster. This formation of antibodies against the biologic happens most commonly in the first year of being on a biologic therapy. When drug levels are low, the medication doesn’t work as well. However, researchers found that by combining a biologic with an IMM they were able to reduce the rate of formation of antibodies, reduce the clearance of the biologic therapy, and produce better drug levels. It is important to maximize the durability of biologics because they are the most effective therapies currently available and many people need to use them long term. A combination of biologic medication with an IMM is the treatment of choice for at least the first year of using a biologic.

Crohn’s disease is a spectrum of diseases. Each individual with Crohn’s will experience the disease differently. This is in part due to the many different inflammatory molecules involved in the disease process. The types of biologic medications discussed so far reduce inflammation by targeting TNF. However, there are other, newer biologic medications that treat Crohn’s disease in a similar way by acting on different molecules, such as adhesion molecules, in the body. A new drug called vedolizumab was introduced in 2015 and works by preventing leukocytes (white blood cells that are key players in the body’s immune system) from adhering to the blood vessels of the gastrointestinal tract and exiting from the blood vessels from the gut to cause intestinal inflammation. Another new biologic drug that blocks white cell activating molecules IL-12 and IL-23, called ustekinumab, may be approved for Crohn’s disease as early as late 2016.

Accelerated Treatment

We now know that treating inflammation earlier in the disease course is better than waiting to start drug therapy. Why? Because inflammation can lead to fibrosis (or ‘scarring’) of the bowel, which does not respond to drug therapy and must therefore be surgically removed. The most effective medications for healing inflammation in the lining of the intestines are biologic medications, such as Remicade or Humira. Originally, biologics were typically used many years (e.g. 10 years) after a person was diagnosed with Crohn’s disease, often after many courses of prednisone and often after their disease had become so bad that their physician decided to use a biologic. As more and more experience has been gained with the use of steroids, IMM and biologics to treat Crohn’s disease, it has been shown that using biologics earlier leads to higher rates of intestinal healing and reduced rates of complications such as surgery.

Maintaining good control of inflammation throughout your disease helps prevent serious complications in the future. It is important to be on a medication that is effective for you. If a treatment is not effective (clear evidence of control of inflammation) within four months of starting, you need to consider switching to another treatment.

Surgery

Medications such as biologics, steroids or IMM may not control all of a patient’s symptoms. This is because some symptoms result from complications due to inflammation. For example, inflammation leading to scar tissue may cause a stricture (narrowing) in the bowel which can cause pain. Surgery is required to correct the stricture. If left too long without treatment, penetrating complications can arise including:
• A hole in the bowel wall (called a perforation)
• Infection or abscess (collection of pus) due to the bacteria in the fecal material that escapes the bowel
• Fistula, an abnormal tract formed between the gut and another part of the body

Previously, surgery on the small and large intestines for Crohn’s disease was delayed at all costs. However, this approach can lead to the need for emergency surgery to manage the complications above. Recently, it has been recognized that although unnecessary surgery should be avoided, sometimes planning a surgery in advance to remove scar tissue before it can cause complications is the best choice for patients. Elective surgery to remove scar tissue has a reduced mortality rate (0.5%) compared to emergency surgery (5-10%). Overall, the risk associated with elective surgery is lower for the patient than the risk of emergency surgery.

Laparoscopic surgery may be an option for those patients who do not have penetrating complications prior to surgery. Laparoscopic surgery is a minimally invasive operation done through small incisions in the abdomen. Compared to open surgery, laparoscopic surgery results in shorter hospital stays and fewer adhesions after surgery.

Using anti-inflammatory medication after surgery can help reduce inflammation even further and prevent more scar tissue from forming. Ultimately, combining elective surgery with biologic medication has been shown to prevent recurrence of the disease . For these reasons, the current approach to surgery is to avoid emergency surgeries, plan in advance when an operation is necessary, and follow up with medications to reduce relapses.

Summary

Great advancements have been made, and continue to be made, in the management of Crohn’s disease. Firstly, treatment is now focused on treating the cause of symptoms such as inflammation and scarring in addition to symptom management. Instead of using medications like steroids and immunomodulators that broadly suppress the body’s whole immune system, patients are benefiting from biologic medications that specifically target inflammation in the intestines which promotes healing. Biologics are now being used earlier in the disease course and even after surgery for inflammatory bowel disease. When medication alone is not enough, surgery is timed to reduce complications from inflammation and scarring in the intestines. Although there is no known ‘cure’ for Crohn’s disease, much progress has been made to develop the best treatment available. Research continues to investigate this complex disease in the hopes that emerging treatments will further improve the lives of patients.

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