麻豆传媒

ORLANDO -- Despite improvements such as new drug therapies, challenges remain in the management of severe Crohn's disease, a researcher said here at the annual Advances in Inflammatory Bowel Disease meeting.

One of the important current challenges is to distinguish disease activity from disease severity, said David T. Rubin, MD, of the University of Chicago. Activity is how the patient is doing right now, whereas severity also includes their prognosis, he explained.

"If you have a patient in your office who is in remission today but has severe disease or a poor prognosis because of risk factors, you're taking a chance by waiting for the patient to fail a therapy. That's not how we should be managing chronic progressive disease," he said.

Severe activity can be defined as sepsis, dehydration, weight loss, poor growth or development, active perianal disease, or obstruction, whereas severe disease/poor prognosis is defined as younger age at onset, smoking, perianal or penetrating disease, steroid requirements, and the need for surgery at presentation.

"If a patient claims to be feeling fine but has severe prognostic factors, you should stratify them to more careful follow-up," he cautioned.

Therapy today should be focusing on treat-to-target, which should be individualized and the target will not be the same for every patient with Crohn's disease. "We aim for what is reasonable, appropriate, and functional for the specific patient," he said.

This will involve serial disease assessments and adjustment to therapy if the patient has not achieved the objective target.

A second important challenge with Crohn's disease today is the potential for undertreatment. One aspect of this problem is using therapies that have not been shown to modify the disease or achieve an intended goal, such as using 5-aminosalicylic acid (ASA) for penetrating disease, which is safe but won't modify the disease.

Another way of undertreating is through underdosing current medications such as thiopurines, and once again, serial assessment is critical. "Don't settle. Don't let your comfort with the safety of the medication be a substitute for confirming its efficacy," Rubin said.

An additional aspect of undertreatment would be ignoring rectal inflammation and deep ulcers. Even if the patient doesn't have severe symptoms, treatment for this aspect of disease should be aggressive and response closely evaluated, because once perianal Crohn's develops it can be irreversible and is associated with very poor quality of life.

A further challenge is overtreatment. "We don't talk enough about this, but it certainly has many implications for safety and cost," he noted.

One aspect of this is the overuse of steroids, which are still used too often and tapered for too long. "Adrenal insufficiency is rare. If you understand how steroid-sparing therapy works, you should be able to taper steroids to coincide, adjusting treatment to get them off steroids earlier," Rubin said.

It's also not helpful to recommend that every medical therapy be exhausted before the patient is sent to surgery. For example, for someone with a limited ileal structure, post-operative management can be more successful than trying to persist with medical therapy.

Another example of overtreatment could be therapeutic intensification that is unrelated to bowel inflammation, such as treating comorbid irritable bowel symptoms with additional immune suppression.

Excessive treatment could also include using treatment endpoints that are too difficult to achieve and might not necessarily benefit clinical outcomes. "In other words, perfect may be the enemy of good enough," he said.

Further potential for overtreatment is with the use of combination therapy. The from 2010 found that infliximab (Remicade) plus azathioprine was superior at week 26 for clinical and mucosal healing, but experience since then has shown that the improved outcome was more about the pharmacokinetics and levels of infliximab than about actual synergy with azathioprine, he said. Patients in the monotherapy infliximab arm with high trough levels did just as well as patients on the combination.

Combination therapy is also unlikely to be needed with ustekinumab and vedolizumab because of the low immunogenicity associated with these agents. "And keep in mind that if you're using unnecessary combination approaches, you will also be exposing the patient to more adverse events," he advised.

A final but very important challenge in severe Crohn's disease is a lack of communication. "We don't do enough to talk about anxiety, depression, sexual function, and personal relationships. We need to screen for these things and have resources to refer. If these are not addressed, a patient with well-controlled disease can end up in a disabled state."

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