Early, tight control of Crohn’s disease may have lasting benefits – Harvard Health Blog

The gastrointestinal (GI) tract is a remarkable organ: it resides inside our body, but is in regular contact with the outside world because of what we ingest. It’s pretty amazing that immune cells in the digestive tract aren’t activated more regularly by the many foreign products that it encounters every day. It is only when the digestive tract encounters an intruder that may cause disease that immune cells in the digestive tract kick in.

This is, of course, under normal circumstances. In people with Crohn’s disease, normally tolerant immune cells in the gastrointestinal tract are activated without provocation, and this activation leads to chronic or recurrent – but ultimately uncontrolled – inflammation.

Crohn’s disease: an introduction

First described by Dr. Burrill B. Crohn and colleagues in 1932, Crohn’s disease is a complex inflammatory disorder that results from the misguided activity of the immune system. It can involve any part of the gastrointestinal tract, from the mouth to the anus, but most often involves the end of the small intestine.

Depending on the precise location of the gastrointestinal inflammation, Crohn’s disease can cause a number of symptoms, including abdominal pain, diarrhea, weight loss, fever, and sometimes blood in the chest. stool.

Crohn’s disease treatment options have evolved dramatically since Dr. Crohn and his colleagues first described the disease, but the basic premise has remained the same: reduce inflammation out of control. The earliest treatment approaches involved nonspecific anti-inflammatory drugs such as corticosteroids, which have many potentially serious side effects outside of the intestines.

Today, there are a number of newer therapies that work more specifically on the immune system to target inflammatory pathways known to be active in Crohn’s disease. These newer drugs, called biologics, are antibodies that block proteins involved in specific inflammatory pathways linked to Crohn’s disease. However, because we don’t fully understand which pathways are involved in which patients, choosing a drug for a given patient is as much an art as a science.

There is growing evidence for early and aggressive treatment of Crohn’s disease

The first approaches to treating Crohn’s disease followed a progressive algorithm in which new drugs would only be used if the patient did not benefit from established therapies. This sequential approach – called step therapy – has been called into question more recently, as studies have repeatedly shown that newer Crohn’s disease drugs are more effective than the old standards and have preferable side effect profiles. . Research also indicates that early and aggressive intervention and treatment, targeting not only symptoms but objective evidence of inflammation (assessed by blood work, stool tests, imaging and endoscopy), lead to better health and a better quality of life, at least in the short term. term.

Researchers recently published a study in the journal Gastroenterology on the long-term benefits of treating patients with Crohn’s disease to reduce both symptoms and inflammation. Specifically, they analyzed follow-up data from patients enrolled in the CALM study – a multicentre trial that compared two treatment approaches for early, moderate to severe Crohn’s disease. In the first approach, the decision to intensify treatment was based solely on symptoms; in the other approach, the decision was based on both symptoms and objective evidence of inflammation (found in blood tests or a stool test, for example). This second approach is called strict control. A patient under close control might feel fine, but treatment would be stepped up if there was objective evidence of inflammation. The primary end point of the original CALM study was healing of the inflamed lining of the intestines, and the data showed that the tight control approach to treatment was more effective in achieving this goal.

the Gastroenterology The study took the results of the original CALM study even further. The researchers looked at how patients who managed to heal their intestinal lining performed several years later. To this end, the researchers looked at the rates of various adverse outcomes (including the need for surgery and hospitalization for Crohn’s disease) in patients in the CALM study since the end of the trial.

They found that patients who felt well and who had demonstrated healing of the intestinal lining (called deep remission) had a significantly decreased risk of progression to Crohn’s disease. Healing of the intestinal lining without feeling well and a feeling of well-being without healing of the intestinal lining was also associated with a lower risk of disease progression compared to patients with active symptoms and inflammation, but in to a lesser extent.

Study results may not generalize to many patients with Crohn’s disease

The recent study strengthens a growing body of evidence to support a treatment approach that emphasizes early intervention aimed at healing the lining of the intestines and resolving symptoms. Can we generalize the results to most patients with Crohn’s disease? Not necessarily.

The patients enrolled had never been treated with a newer biologic drug, or with a drug called an immunomodulator that affects the functioning of the immune system, before enrolling in the CALM study. Immunomodulators have been used to treat inflammatory bowel disease (IBD) since the 1960s, and they are often one of the first classes of drugs used for the treatment of IBD. As a result, these study results may not generalize to many people who have been diagnosed with Crohn’s for long enough to have previously been treated with an immunomodulator.

In addition, those who received intensified treatment were treated with increasingly optimized doses of a single biologic, adalimumab (Humira). It remains to be seen whether we would see the same results in patients already exposed to one biologic or with the use of another biologic.

Doctor-patient collaboration is essential for the success of Crohn’s treatment

In my practice, I regularly encourage the early use of highly effective therapies to maintain tight control. For some, the decision to follow this approach is easy. For others, the idea of ​​stepping up therapy, perhaps without symptoms, and targeting something they may not be feeling, is more difficult to convince. Among the barriers are concerns about side effects and the need for frequent monitoring.

Working with my patients so that they can make medical decisions that are consistent with their values ​​but still informed by evidence is essential for success, as is a commitment to regularly review and rethink the approach over time.

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Jothi Venkat

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