New Ways for Coping with Crohn’s Disease

Biologics have been effective for many patients, but not for all. New drugs, with new mechanisms of action, promise more help and hope.

Crohn’s disease is an inflammatory bowel disease (IBD) affecting the lining of the digestive tract, often spreading deep into the lining of the affected organ. The cause of the disease remains a subject of investigation. Research has confirmed that the GI-inflammation of Crohn’s disease involves several factors: genetics, the patient’s immune system and antigens in the gut environment.

Crohn’s is considered a chronic disease, without cure. “But we do have an increasingly broad array of treatments that can alleviate patients’ suffering in the long term, and even push the disease into remission,” says Dr. Sunil Khurana, co-CEO of Premier Medical Group and director of the GI Division.

Among the newest medications available are the so-called biologics. Infliximab (Remicade) was the first substance specifically approved (in 1998) for the treatment of Crohn’s disease. It, and subsequent drugs, such as Humira and Cimzia, target and suppress tumor necrosis factor (TNF), a protein implicated in creating the inflammation responsible for many of the most debilitating symptoms of Crohn’s disease.

These biologics have been shown to be highly effective for many patients, inducing remission and maintaining it for periods of a year or longer.  In some of our patients, however, we observed a strong initial response to therapy that diminished over a period of maintenance treatment. Initial research suggested two main potential causes for this phenomenon.

It was possible that non-responding patients were mounting an immunogenic response against the TNF agent, creating antibodies against the antibodies. To combat this, we now prescribe concurrent immunomodular therapy for the majority of patients taking anti-TNF drugs.

It was also possible that some patients were metabolizing the drug in a manner that made them unable to maintain the proper level of the drug in their bloodstreams.  “Among the most exciting recent developments in our field is the new ability to measure the level of a drug in a patient’s body and determine whether he or she is receiving the right dose for their condition,” says Khurana. Before the advent of therapeutic drug monitoring, “Everybody started with the same dosage at a set interval. If the patient did not respond to those drugs, we would arbitrarily change the dosage, hoping that there would be a positive response. Now we can accurately measure the levels in patients and fine-tune dosages to their specific needs.” What this also means is that we may find success with these drugs in patients who were originally unresponsive.

There are also significant new developments for Crohn’s patients who have previously failed anti-TNF therapy with one or more drugs. In May, 2014, the FDA approved Entyvio (vedolizumab) to treat adults with moderate-to-severe forms of Crohn’s disease. This humanized monoclonal antibody has a different mechanism of action than do TNF blockers. It targets proteins called alpha-4-beta-7 integrins, the molecules on inflammatory cells that cause them to adhere to the gastrointestinal tract.

Also promising for TNF-nonresponders, but still undergoing clinical trials, are monoclonal antibodies that target interleukin 12/23, T-cells that mediate the body’s inflammatory pathways.

“Premier’s Gastroenterology Division is deeply involved in a number of clinical studies designed to test drugs whose mechanism of action is different than recently approved drugs such as Remicade and Humira. We are doing research that will ultimately help our Crohn’s disease patients,” says Khurana. “Research is important to the development of new, safe medications with better efficacy. Without it, we would not have any medical advances and nothing new to offer the people who turn to us for help, and hope.”

 

 

 

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