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Enteral Therapy on Trial

November 10, 2014

Making the case for enteral therapy in pediatric Crohn's disease.

Micah Cohen sat down at the dining room table in his family’s Columbus, Ohio, home and took the first sip of a new therapy he hoped would relieve the symptoms of his Crohn’s disease. The thick, sweet chocolate shake, rich with nutrients, felt heavy in the 14-year-old’s stomach. Can I really drink six of these a day for the next 12 weeks?he wondered silently. Will my friends tease me every time I gulp down a bottle of Ensure® in the school cafeteria? More importantly, will this make me better?

When Micah’s family first read about the therapy, called enteral nutrition, used to induce remission for Crohn’s disease, it was a rarely prescribed treatment plan in the United States, despite its widespread use in Europe, Great Britain, Japan and elsewhere. Now, following a published statement by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition endorsing the therapy, more U.S. doctors are acquainting themselves with enteral therapy as a first-line option for their pediatric Crohn’s patients.

For Micah, it offered a welcome alternative to the intense series of hours-long drug injections he would otherwise face for acute relapses. First diagnosed with Crohn’s at age 11, Micah had been taking a chemotherapy medication called 6-mercaptopurine (6-MP) to manage his disease. It kept him in remission for two years, until he experienced a flare-up that even increased dosages were unable to control. When his growth and weight started faltering as well, an MRI confirmed his disease was active and severe. The prospect of a lifetime of immunosuppressant and steroid treatments left Micah and his parents ready to try something else.

Studies suggest that enteral nutrition by mouth or nasogastric tube is as effective for pediatric Crohn’s as steroids — without the same side effects. But the majority of U.S. physicians still rely on drugs to treat children’s flare-ups. As Micah drained that first can of Ensure®, he didn’t know what to think about the therapy.He thought back to his last episode of Crohn’s inflammation — the cramps in his gut, the mood swings, the feelings of futility. Could an over-the-counter meal replacement drink be the wonder drug he’d been hoping for?

A Review of the Evidence

Pitting nutritional shakes or at-home tube feeding against potent pharmaceuticals may seem like a naïve approach to therapy for a chronic inflammatory condition of the gastrointestinal tract. With Crohn’s, the entire thickness of the intestinal wall can be involved and any part of the GI tract — from mouth to anus — can be affected. As many as 70,000 children in the United States have the disease, with symptoms ranging from intestinal bleeding and persistent diarrhea to malnutrition and fevers.

Traditionally, patients with moderate to severe cases receive short-term corticosteroids during a Crohn’s flare to reduce inflammation and calm the immune system. With extended use, however, the drugs can stunt growth and cause hair loss, insomnia and a number of other undesirable side effects. Furthermore, they do not heal the mucosal lining of the gastrointestinal tract — a key disease severity indicator in Crohn’s disease.

Immunomodulators are typically prescribed to maintain disease remission in children. These drugs help reduce dependency on steroids but carry their own risks, including increased susceptibility to infections, nausea, inflammation of the pancreas or liver and even a heightened risk of certain cancers.

The condition is monitored by regular blood tests that look for increased levels of inflammatory markers that signal a flare up. In many cases, the drugs are effective at inducing or maintaining remission. But the severity of the side effects and the appeal of treating a GI condition with nutrition have led many researchers to investigate enteral therapy’s potential.

Studies published in the Cochrane Database System Review, the Journal of Pediatric Gastroenterology and Nutrition, Inflammatory Bowel Diseases, Gut and elsewhere have concluded that near-exclusive or exclusive enteral nutrition (EEN) can induce remission of Crohn’s in pediatric patients. Researchers have found that the therapy and steroids are about equivalent in their effectiveness, although children respond to enteral nutrition better than adults with Crohn’s. The exclusively liquid diet requires that 90 to 100 percent of the child’s calories come from either a standard meal-replacement shake, such as Ensure® or Boost®, or a prescription formula containing broken-down proteins. Studies suggest it is effective in up to 90 percent of pediatric patients, particularly if the therapy begins shortly after diagnosis.

The mechanisms behind the effectiveness of enteral therapy are not completely understood, says Sandra Kim, MD, medical director of the Inflammatory Bowel Disease Center at Nationwide Children’s Hospital. However, she and other proponents of enteral therapy are less concerned about the precise biochemical mechanism than the safety profile of the treatment and the clinical outcomes their patients achieve.

EEN may be offered for 8 to 12 weeks to reduce inflammation, initiate mucosal healing and induce remission. Its effectiveness in partial use as a maintenance therapy is less established, though early research is promising. Side effects are limited to nausea or an uncomfortable feeling of fullness, which most patients can overcome by adjusting how quickly or at what intervalsthey drink the shakes, and it has the considerable benefit of reversing malnutrition and growth delays due to Crohn’s patients’ inability to absorb nutrients normally.

Despite these findings, fewer than 12 percent of U.S. pediatric gastroenterologists currently recommend enteral therapy as a treatment option to patients experiencing Crohn’s flare-ups, compared to nearly two-thirds of European specialists.

The success of the treatment in other countries has led some U.S. families, including Micah’s, to request the alternative treatment even before doctors offer it.

“When we first asked about enteral nutrition, Micah’s doctors didn’t feel comfortable recommending it as a treatment,” says Donna Cohen, Micah’s mother. The family decided to try enteral therapy anyway, while following the drug regimen recommended by Micah’s physician, but couldn’t maintain an effective EEN protocol on their own. “When they did start offering it as a prescribed therapy, it was so much easier — their support was essential to giving Micah a real chance to heal using nutrition.”

After just one week on 90 percent enteral nutrition, Micah’s symptoms had subsided significantly, and blood tests showed that two of the three chief Crohn’s disease markers were back in the normal range.

“When I started on the shakes, I felt like I had nothing to lose,” Micah says. “Then I got better so quickly. And when I got used to making the most out of my 250 calories of food per day, I was much happier to be able to use the formula than a serious medication.” That’s how he knew he could manage another 11 weeks of chocolate shakes.

Establishing Precedent

Although Micah’s determination to make it through his initial enteral therapy regimen seems impressive, his response is not unique.

“The medical community has long appreciated the importance of proper nutrition in maintaining health,” says Dr. Kim, who chairs pediatric committees for the Crohn’s and Colitis Foundation of America and the multi-institutional inflammatory bowel disease collaborative called ImproveCareNow. “What is emerging more recently is the key role of specific nutrition-based therapies in targeted disease outcomes.”

Dr. Kim is one of the physicians leading the enteral therapy movement in the United States, speaking nationally about her center’s experiences with EEN. Led by her close collaborator Jennifer Smith, RD, their team of pediatric dieticians and gastroenterologists has developed and shared a protocol for initiating and maintaining the therapy.

“We’ve had considerable success helping our patient population adopt oral enteral therapy as their primary treatment during flare-ups,” Dr. Kim says. “Many families appreciate the non-steroid option and, contrary to popular expectations, have very good compliance with the program.”

Their success is not an isolated occurrence. Children’s Hospital of Philadelphia has also spearheaded the United States’ use of enteral therapy for pediatric Crohn’s, largely through the work of Robert Baldassano, MD, director of their Center for Pediatric Inflammatory Bowel Disease. He has prescribed EEN for dozens of young patients, but his program has achieved its principle successes with an entirely different approach from Dr. Kim’s: nighttime nasogastric tube feeding.

“Long-term compliance is difficult if you expect a child to drink a substantial portion of their caloric needs each day, even if it tastes good,” argues Dr. Baldassano, who has published a number of studies on EEN use for pediatric Crohn’s disease. “We have found that long-term compliance, tension in the household regarding enteral nutrition and the overall success of therapy is better by nasogastric tube.”

Dr. Baldassano uses enteral therapy to control his own severe Crohn’s disease. His personal experience engenders confidence among his colleagues and his patients.

“When I have problems, I use the therapy,” he says. “It has made much more of a difference in my condition than any medication I’ve ever been on — and I’ve been on them all.”

Regardless of whether patients use nasogastric tubes or drink their formulas, actively supporting the families is essential, says Smith, who implemented her enteral therapy protocol at Nationwide Children’s in June of 2013. “We are constantly available for them if they have questions or need more suggestions about managing the diet, but we’re also learning a lot from them,” she adds. “They’re sharing great tips and strategies for making oral EEN work.”

Together with the dietitians, patient families at Nationwide Children’s have built 200-calorie lists for common foods and restaurants and are even creating an Enteral Therapy Cookbook. Tools like these help families adjust to changes in diet and make the most of the limited calories that can come from food each day, Smith says. Experimentation with flavors and texture by adding food-grade essential oils and freezing or blending the formula help add variety, she says. Options for delivery mode, such as through popsicles or poured into a coffee-house tumbler, may also help bring a sense of normalcy to even this unusual diet.

Overcoming the Opposition

Enteral therapy didn’t become part of Nationwide Children’s GI team’s arsenal overnight. Despite Dr. Kim’s vocal advocacy for the therapy, there was some initial hesitation on the part of her department’s physicians.

“Even though everyone understood its efficacy, I think people mainly were uncomfortable recommending it because it was new to them and wasn’t as simple as prescribing a pill,” she says. “But I think they also were hesitant because they didn’t think patients would be able to comply with the diet.”

When Dr. Kim first started promoting EEN in her center a year ago, there were only a handful of patients following the protocol. Now they prescribe it to two patients per week, and their numbers are increasing.

“Many times, families who were considered noncompliant with their prescriptions in the past do much better with the enteral nutrition,” Smith says, “since their prior noncompliance was due to the fact that they just didn’t like their medications.”

Other chief barriers to the uptake of EEN as a first-line therapy include lack of physician training on and exposure to the practice, Dr. Baldassano suggests, and the increased time commitment it requires from a doctor if dietitians or other support staff are not available as patient resources. Furthermore, he says, getting insurance companies to cover it can be a long and arduous process, although Dr. Kim has found a way around that.

“Medical necessity letters to insurers often help,” she says. “But even when they don’t, the over-the-counter cost of the formula doesn’t often exceed the cost of regular meals per month.”

The mystique behind the therapy for physicians who have not yet guided a patient through it is slightly more complicated, however. Although reaching out to large centers with experience in enteral therapy for assistance may help increase comfort levels for physicians before they begin treating patients on their own, Dr. Kim suggests it may also be helpful to try something slightly less conventional.

One such idea is Enteral Therapy Thursday, a program Smith and another dietitian initiated at Nationwide Children’s to introduce the treatment option to medical staff. To understand what Crohn’s patients experience on EEN, every member of the GI team — dietitians, nurses and clinicians — spent an entire day on 90 percent enteral nutrition, trying a variety of formula flavors and coming up with their own choices for their solid food calorie allotment. The insight the staff gained was tremendous, says Dr. Kim.

“It’s pretty rare that physicians can try out a therapy just to see how it feels, without having to worry about adverse effects,” Dr. Kim explains. “But this option isn’t a drug. It’s just nutrition with the power of a medicine and virtually none of the negatives.”

This type of hands-on experience may help doctors better assist patients, she says, since physician commitment and willingness appears almost as crucial for patient success as family motivation. “It’s hard to tell a patient that 90 percent of their calories need to come from these shakes instead of from food,” Dr. Kim says. “But if the physician believes in maximizing the outcome while minimizing side effects, enteral therapy is a way to do it.”

Dr. Kim also encourages practitioners new to EEN to follow protocols developed by CHOP and Nationwide Children’s and draw on the resources of organizations such as the North American Society of Pediatric Gastroenterology, Hepatology and Nutritionand ImproveCareNow. Doing so may help bring enteral therapy into the realm of common first-line care for pediatric Crohn’s, and eventually, Dr. Kim forecasts, for maintenance therapy as well.

“I’m looking forward to the day that enteral therapy is the norm,” she says. “The reduction in side effects and the avoidance of pharmaceuticals may be enough to interest many families in attempting it for inducing remission or for long-term use.”

For patients with a lifelong condition such as Crohn’s, enteral therapy may never appear “normal” to the rest of the world, and Micah, for one, knows that. He just doesn’t care. Having maintained a 60 percent enteral nutrition diet for over six months, Micah does not plan to go back to a regular diet. Ever.

Although his experience may not be typical, Micah has already been weaned off his maintenance medication and his disease has been in clinical remission since he initiated EEN. He simply increases the percentage of his calories from formula temporarily if his regular lab testing indicates a rise in disease markers. “I can imagine that, eventually, the shakes or just a careful diet will be my only therapy for Crohn’s,” Micah says.

Dr. Baldassano shares his optimism. “In the future, enteral therapy will be used as the primary treatment for IBD flares,” he predicts. “I would even go so far as to say that it will be used to prevent IBD problems.”

Lend us your voice. What would persuade you to prescribe enteral therapy for a Crohn’s patient?

 

References:

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