July 16, 2018

Medical Update: New Therapies Target Inflammatory Bowel Disease

By: Kasey Fuqua

As the number of patients with inflammatory bowel disease (IBD) grows, so does the number of effective, targeted treatment options.

For almost 20 years, monoclonal antibodies have been the main therapy patients with moderate to severe IBD. These medicines typically suppress inflammation in reaction to tumor necrosis factor (anti-TNF agents). While these drugs can help many patients, they don’t provide consistent relief for all patients with IBD.

Jeremy Domanski, MD

“Not every patient is going to respond to anti-TNF therapy, and some of these patients are really difficult to treat,” says Jeremy Domanski, MD, gastroenterologist at Gastroenterology Associates of Tidewater and Chesapeake Regional Medical Center. “The newer agents give us unique targets for treatment so we can better tailor therapy for patients.”

Newer monoclonal antibodies, such as vedolizumab, help prevent white blood cells from travelling to inflammation in the gut while others, such as ustekinumab, target pro-inflammatory cytokines. Though not all of these newer medications are approved for use in children, monoclonal antibodies still play a growing role in pediatric treatment.

“Sometimes we still have to use newer biologic agents when our first line medications have failed and kids still have issues,” says Michael Konikoff, MD, a pediatric gastroenterologist with Children’s Specialty Group, PLLC, at Children’s Hospital of the King’s Daughters. “Medicines that once worked for them no longer do, so we have to continually find new ones. About half of our more than 300 patients use monoclonal antibodies. In the past, it would have been a smaller proportion.”

While these new agents give patients more targeted treatment options, they also help them avoid the damaging side effects of long-term steroid use. Though patients using monoclonal antibodies do have a higher risk for infection or infusion reactions, overall the benefits of these drugs outweigh any potential risks, especially for patients with severe IBD.

For children with inflammatory bowel disease, the risk of side effects is especially important to consider.

Michael Konikoff, MD

“A lot of the same treatments are used between pediatrics and adults,” says Dr. Konikoff. “However, we use slightly different approaches just because when we diagnose a child with inflammatory bowel disease, we may be looking ahead to 70 or 80 years of life. We have to take that into account in terms of treatments we recommend.”

Both adult and pediatric patients with IBD in Hampton Roads have access to new treatments through clinical trials. At Gastroenterology Associates of Tidewater, patients are enrolled in trials to test medicines that target different aspects of the inflammatory process than drugs currently on the market. Janus kinase (JAK1) inhibitors affects signaling between cytokines and can be taken orally, instead of through injection or infusion. Other monoclonal antibodies in testing target different interleukins than current drugs.

“The biggest benefit for our patients is that we will have additional targets for therapy,” says Dr. Domanski. “If patients fail one drug, we’ll have options to give them a different targeted therapy.”

At CHKD, gastroenterologists participate in national research through the quality improvement network called Improve Care Now. Around 100 pediatric IBD treatment centers across the country design and participate in large-scale studies that offer promising data for the future of IBD treatment.

“I think participating in research has really energized our practice,” says Dr. Konikoff. “The strides we’ve been able to make for our patients in terms of remission rates and keeping kids in better health has been pretty amazing.”

Effective Therapies Delay—or Eliminate—the Need
for Surgery
Targeted therapies and advances in laparoscopic techniques are also helping patients with IBD avoid or delay more invasive surgical treatment.

“The medicines we have now have improved to the point where many kids who would have had surgery previously can now avoid it because we can keep their inflammation under better control,” says Dr. Konikoff.

Around 70 percent of patients with Crohn’s disease and 33 percent of patients with ulcerative colitis eventually require some form of surgical treatment.

“One of our goals as GI doctors is try to prevent surgery or at least to delay it when we can,” says Dr. Domanski. “Clearly there are patients who are going to benefit from surgical intervention, so we have to work closely with surgeons.”

Endoscopic procedures like balloon dilations of strictures in Crohn’s disease or endoscopic resection of visual dysplastic lesions in the colon offer patients some relief without invasive surgeries. These procedures offer quicker recovery times and less pain than surgeries used in the past.

Surgeries such as bowel resection can improve quality of life for patients with severe Crohn’s disease. However, up to 50 percent of these patients will require another surgery in the future due to recurrence within 5 years.

The Future of Noninvasive IBD Diagnosis
Just as surgeries become less invasive, researchers are working toward less invasive techniques to diagnose IBD. While colonoscopy and biopsy are the current hallmarks in IBD diagnosis, imaging techniques and laboratory testing continue to play a more prominent role.

Small bowel imaging using MRI or CT scans, as well as capsule endoscopy, allow physicians to study the small bowel and better identify patients with IBD who may not have colon disease. In some cases, gastroenterologists can also detect gut inflammation using fecal calprotectin and lactoferrin testing.

In the future, these stool-based tests may be enough to diagnose IBD without endoscopy. However, there is not currently enough data to use these tests alone.

“I think something like fecal calprotectin shows promise as a less invasive screening test,” says Dr. Domanski. “We see patients that have a variety of bowel complaints who come to the primary care provider. It would be helpful to have a less invasive marker looking for inflammatory bowel disease rather than going directly to something like colonoscopy.”

Diagnosing children with IBD can be especially challenging as they may not show symptoms, such as diarrhea or blood in stool, the way adults do. Instead, children may only show signs of growth failure, even if they have had IBD for years.

Dr. Konikoff encourages primary care providers to keep in mind that children may not show obvious symptoms and consider less invasive stool or blood testing to screen for the condition before referral to a pediatric gastroenterologist.

The Possible Role of Diet in IBD
Gastroenterologists and dietitians on their staff may also help patients manage nutrition during flare-ups or to promote growth in children. Though patients may try many diets, such as carbohydrate-specific diets or dairy-free diets, no research currently backs any specific dietary therapy to manage IBD.

“We are starting to see more of a focus in research on diet and how that interacts with Crohn’s disease,” says Dr. Konikoff. “There are some newer studies that we are participating in looking at the role of diet in Crohn’s disease. Moving forward, I wonder if that will become a larger part of our treatment arsenal.”

Research at CHKD currently focuses on variants of the specific carbohydrate diet. While it is still too early to recommend the diet to all patients, the research is offering valuable insights on how to use diet alongside medications.

As researchers and physician develop more targeted medications, diets and surgeries for IBD, patients can expect to experience better quality of life and management of these conditions.