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While some brides-to-be spend the week before their big day worrying about the weather or fitting into their dress, Danielle Kroft was dealing with a flare-up of her ulcerative colitis (UC). And a wedding dress wasn’t exactly going to make the situation easier.

“I couldn’t imagine being stuck in that dress for nine hours,” Kroft recalled. “So I was in my doctor’s office begging him to give me anything and everything to get it under control.”

This is what life is like for more than 900,000 people in the United States living with UC, an unpredictable inflammatory bowel disease (IBD) with symptoms that come and go over time. Some patients go years without symptoms; others have frequent flare-ups. In a survey, almost two-thirds of patients feel like UC controls their lives.

While more people are being diagnosed with IBD, Kroft believes that there is hope to accepting and managing the chronic disease. She has been reluctant to talk about her UC but is sharing her story for this year’s World IBD Day (May 19) to raise awareness so others can learn to better manage their disease.

A WEEK BEFORE HER WEDDING DAY, DANIELLE KROFT HAD A FLARE-UP OF HER ULCERATIVE COLITIS THAT THREATENED HER PLANS. PHOTO CREDIT: TARA WILEY PHOTOGRAPHY

A WEEK BEFORE HER WEDDING DAY, DANIELLE KROFT HAD A FLARE-UP OF HER ULCERATIVE COLITIS THAT THREATENED HER PLANS. PHOTO CREDIT: TARA WILEY PHOTOGRAPHY

Dinner Table Conversation Non-starters

When Kroft began noticing blood in her stool and experiencing abdominal pain at the age of 14, she didn’t tell anyone at first, thinking—or maybe hoping—that it would go away on its own. After all, the symptoms are hardly appropriate for the dinner table. But as the symptoms continued, Kroft eventually confided in her mother, who scheduled a doctor’s appointment. Five months, multiple doctor visits and a colonoscopy later, she was diagnosed.

“When you are 14, you don’t know what symptoms you should be watching for,” Kroft said. “Part of the reason that it took so many months to be diagnosed with UC was that I wasn’t sharing all the information about my symptoms with my doctors.”

This experience is common; in a survey, 45 percent of patients with UC regret not sharing more information with their doctors during visits. UC is most frequently diagnosed between the ages of 15 and 30, when patients may feel self-conscious talking about symptoms such as bloody stools, diarrhea and urgent needs to use the toilet.

When Kroft’s sister was diagnosed a couple of years later—genetic factors are thought to play a role in the disease—Kroft felt like she had someone close to her who could relate. But she also learned first-hand that no two people with UC have the same experience.

“Our food triggers, for example, are very different,” Kroft said. “I can eat bananas, but they upset her abdomen. I don’t do well with pancakes, but for her, pancakes aren’t a problem. And I really like pancakes.”

When you have a chronic illness, you need to take your medicine and build in time for blood work and doctor visits.

Things Only Got Harder

Being diagnosed with UC was just the start of Kroft’s lifelong struggle to control the disease, which is the best that she can hope for with no current cure. Instead of worrying about what shoes she was going to wear to school, Kroft had to focus on taking her medication every day or risk getting sick.

Sticking with her treatment plan was not easy. At one point, she was taking 26 pills a day—a mix of over-the-counter and prescription medications and supplements. UC treatment remains a trial-and-error process, and her first few medications didn’t work out. Her treatment plans have included enemas and foams that had to be administered rectally, which she recalls was as uncomfortable as it was embarrassing.

Things only got harder in college. Waking up at 4 a.m. each day for crew practice and the logistics of taking her medications stressed her out. “Where are you going to lay down to take an enema when you’re living in a dorm? Ask your roommate to leave because you have to do that? No way.”

At one point during her sophomore year, she had a month without any symptoms and convinced herself that she didn’t need her medication anymore. She stopped her treatment, which led to a really bad flare-up.

“I broke down emotionally at that point,” Kroft said. “I was young and didn’t take it as seriously as I should have. I didn’t make it a priority.”

AFTER TEN YEARS OF TRYING DIFFERENT THERAPIES, KROFT AND HER DOCTOR FINALLY FOUND A TREATMENT PLAN THAT HELPS HER MANAGE HER UC SYMPTOMS.

AFTER TEN YEARS OF TRYING DIFFERENT THERAPIES, KROFT AND HER DOCTOR FINALLY FOUND A TREATMENT PLAN THAT HELPS HER MANAGE HER UC SYMPTOMS.

Talking Poop

About ten years, multiple medications later, Kroft has finally found a treatment plan that works for her. She also landed a job she loves in public relations and married her high school sweetheart.

She still feels the need to be close to a bathroom during conference calls or while commuting. And she understands that’s always going to be a part of her life. For the most part, she’s feeling well.

“The biggest thing I have realized is that you need to take care of yourself,” Kroft said. “When you have a chronic illness, you need to take your medicine and build in time for blood work and doctor visits.”

Taking good care of yourself means learning more about your chronic disease and getting support, according to Kroft. She wishes she had asked her doctor more questions about the condition and had spent time reading the Crohn’s & Colitis Foundation’s website when she was first diagnosed. Recently, Kroft has begun attending seminars from the Foundation, where she has learned from other patients and experts. She’s presently most concerned with learning the effects, if any, of UC and its treatments on pregnancy.

Over the past 14 years, Kroft has also learned to be more open with people about her disease. She can’t believe she waited six years before thoroughly explaining what living with UC is like to her now-husband. “People are a lot more willing to talk about poop issues and cut you some slack than you might think,” Kroft said.

To learn how combining endoscopic and microscopic analyses is providing a more complete picture of UC, read “A Closer Look at Mucosal Healing in Ulcerative Colitis.”

 

When doctors evaluate if a treatment is working for one of their patients with ulcerative colitis (UC), an inflammatory bowel disease that causes damage to the mucosal layer of the digestive tract, they will ask their patient about symptoms, such as bleeding, diarrhea and pain. But when researchers are evaluating the effectiveness of potential new treatments in a clinical trial, they need to include an objective assessment of disease activity as well.

So researchers are increasingly using endoscopy, a procedure using a flexible tube equipped with a video camera to look at patients’ digestive tracts, and examining tissue samples removed during a biopsy under a microscope to determine how well the mucosa is responding to an investigational therapy. In this Q&A, Dr. Keith Usiskin, executive director at Celgene, explains how by combining these two measurements, an assessment of mucosal healing can be made.

DR. KEITH USISKIN, EXECUTIVE DIRECTOR AT CELGENE, BELIEVES THAT COMBINING ENDOSCOPIC AND HISTOLOGIC MEASUREMENTS PROVIDES A DETAILED VIEW OF MUCOSAL HEALING IN ULCERATIVE COLITIS.

DR. KEITH USISKIN, EXECUTIVE DIRECTOR AT CELGENE, BELIEVES THAT COMBINING ENDOSCOPIC AND HISTOLOGIC MEASUREMENTS PROVIDES A DETAILED VIEW OF MUCOSAL HEALING IN ULCERATIVE COLITIS.

Why is mucosal healing important?

“Ulcerative colitis causes massive damage to the mucosa, weakening blood vessels and, eventually, leading to ulcers. Doctors and researchers are finding that achieving mucosal healing correlates with a better quality of life and other measurable benefits for patients with UC.

“For instance, studies have found that patients with UC in remission and with no signs of microscopic inflammation are less likely to be hospitalized or to experience relapse, in which their UC symptoms return. The data isn’t as strong as we’d like just yet, but we see a definite trend beginning to take shape.”

How is mucosal healing assessed in UC trials?

“Organizations conducting UC clinical trials assess mucosal healing often use both endoscopic appearance — what a gastroenterologist sees regarding redness, inflammation and ulcers during an endoscopy — and histological appearance — what a pathologist sees under a microscope regarding inflammation when they examine a tissue sample from a biopsy.”

Why are both endoscopies and biopsies needed to assess mucosal healing?

“While UC causes mucosal damage continuously, not every part of the mucosa is affected to the same extent. So endoscopies provide researchers with a bird’s eye view of the mucosa throughout the entire rectum and large intestine, including regions that are very inflamed and those that are less so.

“But endoscopic appearance doesn’t tell you everything. Studies have found that up to 24 percent of patients whose mucosa looks good in endoscopic assessments still have evidence of microscopic inflammation when a pathologist looks at a biopsy taken from the mucosa. That inflammation suggests the mucosa still is not fully healed and that the patient is at higher risk for relapses.”

Mucosal Healing: An Increasingly Accepted Endpoint in Studies of Ulcerative Colitis Treatments

What constitutes mucosal healing in these assessments?

“Defining mucosal healing remains one of the biggest challenges in UC clinical studies. The medical community and regulatory agencies have not come to a clear consensus on what constitutes mucosal healing in UC.

“Several scoring systems have been proposed for endoscopic and histologic assessments, but researchers have not decided which should be used. In Celgene’s studies, we use a widely used index for disease activity by endoscopic assessment in UC developed by researchers at the Mayo Clinic and a grading scale for histological assessment in UC developed by Dr. Karel Geboes at the University Hospitals Leuven in Belgium. We classify mucosal healing as a Mayo score less than or equal to one and a Geboes histologic score of less than two.”

What are the challenges in assessing mucosal healing?

“Clinician bias has been one of the most significant limitations in assessing mucosal healing. If the patient says they’re doing great, the clinician is more likely to report that the mucosa looks better, even if it seems the same as before starting treatment. The inverse can be true as well. We use central readers who do not know the patient’s health status to eliminate that bias. They can grade the endoscopies and biopsies based solely on their best judgment and experience.”

“The combination of endoscopy and pathology assessment of biopsies is key to the assessment of mucosal healing.”

Does the invasive nature of this assessment affect patient retention?

“Some patients are hesitant to enter a clinical trial if there are too many colonoscopies or endoscopies. Clinical researchers try to limit that when designing protocols for studies to minimize procedures that patients may find uncomfortable.

“We try to make it clear to patients what is expected of them when they sign up for a clinical trial and limit the burdens as much as possible. But we still have to make these assessments to determine the efficacy of potential new treatment options for UC.”

What could improve the assessment of mucosal healing?

“In the future, we may identify biomarkers that correlate with clinical symptoms, benefits and outcomes for patients with UC. Celgene is participating in an initiative to identify such biomarkers, and one day, noninvasive biomarkers may eliminate the need for endoscopy or biopsies. Imaging techniques such as MRIs and CT scans also may prove useful to assessing mucosal healing in future clinical trials and in the clinic. But right now, the combination of endoscopy and pathology assessment of biopsies is key to the assessment of mucosal healing for both scientific and regulatory purposes.”

To learn more about clinical trials for ulcerative colitis and other inflammatory bowel diseases, read “The Importance of Clinical Trials for Inflammatory Bowel Disease.”

Many of the 1.6 million Americans living with inflammatory bowel disease (IBD) struggle to find an effective treatment, leaving them with pain, fatigue and other symptoms that directly affect their lives but may not be obvious to others. Although more than 380 active clinical trials are exploring investigational treatment options for the two most common forms of IBD—Crohn’s disease and ulcerative colitis—many patients either don’t know of these studies or don’t understand the possible benefits of participating.

As patients and advocates work to bring visibility to this disease during this year’s Crohn’s and Colitis Awareness Week (December 1-7), Dr. Bruce Sands, a gastroenterologist at Mount Sinai Hospital and the Icahn School of Medicine at Mount Sinai in New York, explains why some people living with IBD could benefit from discussing clinical trials with their doctors.

DR. BRUCE SANDS, A GASTROENTEROLOGIST AT MOUNT SINAI Hospital and the Icahn School of Medicine at Mount Sinai IN NEW YORK, EXPLAINS WHY SOME PEOPLE LIVING WITH IBD COULD BENEFIT FROM DISCUSSING CLINICAL TRIALS WITH THEIR DOCTORS.

DR. BRUCE SANDS, A GASTROENTEROLOGIST AT MOUNT SINAI Hospital and the Icahn School of Medicine at Mount Sinai IN NEW YORK, EXPLAINS WHY SOME PEOPLE LIVING WITH IBD COULD BENEFIT FROM DISCUSSING CLINICAL TRIALS WITH THEIR DOCTORS.

Why are some people living with IBD unaware that there are clinical trials for their disease?

“IBD clinical trials usually recruit patients who have active, flaring disease. But many patients on existing therapies who may still be flaring are not being cared for by doctors involved with trials. So these doctors may not be prepared to discuss clinical trials as an option. These patients can consider getting another opinion from a doctor at a medical center that offers IBD clinical trials. A good resource for IBD patients to learn more is ClinicalTrials.gov.”

How do you address patients’ concerns about enrolling in a trial?

“Patients feel more comfortable about enrolling when they understand the process. I try to explain the different stages to them. Such as, in Phase 1, researchers focus on evaluating the safety of a new treatment. A treatment doesn’t get to Phase 2 or Phase 3 until we know more about the medication’s safety. At each later stage, more patients take part, and researchers gain better knowledge of the treatment’s safety and efficacy profile.”

“Sometimes, patients hesitate to take part because they worry they will receive a placebo and be left untreated. I tell them that in almost every IBD trial, the investigational therapy is added on top of their existing medication. So they will not be left untreated. Furthermore, most studies allow all participating patients access to the investigational medication after eight to 12 weeks.”

We continue to see progress by studying investigational medications that may provide patients with better symptom relief and disease control.

What do you tell patients who qualify for a clinical trial?

“I explain that there are two big reasons why they should consider enrolling in a clinical trial. First, a clinical study may give them access to a medication that works for them.”

“Second, if people with Crohn’s disease and ulcerative colitis don’t enroll in trials, we will never see advances in the treatment of these diseases. Voluntary patient participation has been essential to the development of new treatment options over the last two decades and will continue to be so in the future.”

Why is it important that we continue to explore new treatments for Crohn’s and ulcerative colitis?

“We have yet to find a medication that works for every person with IBD. And while some existing treatments may work for some patients at first, their effectiveness can wear off over time. Meanwhile, the incidence of IBD is rising across the globe—in the developed world and also countries such as India and China.”

“Over time, we hope to understand which patients do better with which medications through clinical trials. But at this point, we simply need more treatment options.”

How hopeful are you about the future of IBD treatment?

“More than 200 genes are thought to contribute to the risk of Crohn’s disease and ulcerative colitis. Given that complexity, and how the biology differs from person to person, achieving a cure may be very difficult. While we all hope for a cure someday, we continue to see progress by studying investigational medications that may provide patients with better symptom relief and disease control.”

To learn why targeted therapies could be an important therapeutic option for IBD patients, read “Interest Grows in Targeted IBD Research.”

Many people living with moderately to severely active inflammatory bowel disease (IBD) are looking for additional treatment options to help them to cope with the physical and emotional burdens of their disease. Therapies called biologics that target a protein relevant to the immune system called tumor necrosis factor (TNF) are effective for many IBD patients. However, not everyone responds to these treatments. Now, investigational therapies that target other immune pathways are showing promise in clinical trials.

Dr. Brian G. Feagan, director of clinical trials at the Robarts Research Institute, SAYS the Inflammatory bowel disease medical community is increasingly interested in therapies that target sites of inflammation.

Dr. Brian G. Feagan, director of clinical trials at the Robarts Research Institute, SAYS the Inflammatory bowel disease medical community is increasingly interested in therapies that target sites of inflammation.

As more data on these IBD therapies come out of this year’s World Congress of Gastroenterology at ACG2017, Dr. Brian G. Feagan, director of clinical trials at the Robarts Research Institute, explains why the medical community is increasingly interested in therapies that target pathways associated with inflammation in the two most common forms of IBD, ulcerative colitis and Crohn’s disease.

Why is it important to develop targeted therapies for patients with IBD?

“Before biologic therapies were approved for IBD, we relied on steroids and immunosuppressive agents that broadly suppressed the immune system. We didn’t know exactly how these treatments worked but did know that they hit many different pathways. They were not very selective. For some patients whose ulcerative colitis or Crohn’s disease is caused by a particular pathway, these broad-spectrum agents may or may not hit that pathway, leaving some IBD patients without an effective treatment.”

People feel like they cannot plan their lives with the disease, but the continued investment in research is giving them hope.

How did the biologics change IBD treatment for patients?

“The biologics target a single protein that plays a role in the development of IBD, called TNF. Before the success of these anti-TNF therapies, the medical community didn’t think that blocking a single molecule or pathway would be effective. They believed that a combination of pathways was responsible for disease and that broad-spectrum therapy was needed. Clinical trials proved that theory wrong, at least for some patients. We have learned a lot about TNF blockers in the last 20  years.”

To learn why researchers must continue to explore new treatment options for IBD, read the “World IBD Day: Current Treatments for IBD Not Meeting Patient Needs” infographic.

To learn why researchers must continue to explore new treatment options for IBD, read the “World IBD Day: Current Treatments for IBD Not Meeting Patient Needs” infographic.


How have advances in understanding IBD opened the door for additional targeted therapies?

“Now that we know a single pathway can make a difference, as with TNF, researchers have started to look for other specific pathways associated with IBD. We are learning more about how these pathways control the immune response, interact with bacteria in our gut and are associated with complications of the disease, such as blockages in the intestine (strictures) and inflammatory tracts between the bowel and other organs, most commonly the skin (fistulas). This focus on specific pathways has evolved out of oncology, where researchers look for disease-related pathways and then use therapies that target specific pathways in individual patients. We haven’t quite gotten there in IBD, but that is the goal.”

Why is new research important for patients?

“People with ulcerative colitis and Crohn’s disease deal with substantial mental and social disabilities. The embarrassment of having IBD can negatively affect their lives. People feel like they cannot plan their lives with the disease, but the continued investment in research is giving them hope.”

To learn why researchers must continue to explore new treatment options for IBD, read the “World IBD Day: Current Treatments for IBD Not Meeting Patient Needs” infographic.

It’s not rare for a patient to be told they have ulcerative colitis only to later find out that they instead have Crohn’s disease.

“It’s difficult for doctors to make a proper diagnosis sometimes because Crohn’s can look very similar to ulcerative colitis,” Dr. Giovanni Monteleone, a gastroenterologist at the University of Rome Tor Vergata, said.

Shared characteristics include diarrhea and abdominal pain caused by inflammation of the digestive tract, but the location of this inflammation differs. In ulcerative colitis, inflammation only affects the large intestine, starting with the rectum—which is located in the lower left abdomen. Meanwhile, Crohn’s disease most commonly involves the terminal ileum—located in the lower right abdomen—although it can affect the entire gastrointestinal tract as well.

Crohn's Disease vs. Ulcerative Colitis

And while ulcerative colitis works its way from the rectum through the colon continuously, Crohn’s disease can cause patches of inflammation surrounded by healthy spots. That patterning can only be identified through a colonoscopy to view the inner lining of the large intestine. Even with this invasive test, about 10 percent of cases are still unclear.

Genetic studies are no help in the matter. “The genetic alterations associated with these diseases are common to both,” Monteleone said. “So we have no genetic diagnostic test to single out a colitis or Crohn’s diagnosis.”

What’s left, then, is simply time. “In those cases, the patient will eventually be diagnosed with one disease or the other as evidence mounts,” Dr. Guillermo Rossiter, senior director of Inflammation and Immunology R&D at Celgene, said.

We have a long way to go in terms of helping the most patients with medical therapies.

For instance, some patients develop anal fistula and fissures—areas of tunneling and painful cracks in the skin around the anus. “That’s a sign that we’re dealing with Crohn’s disease and not colitis,” said Dr. Faten Aberra, a gastroenterologist at the University of Pennsylvania and a committee member at the Crohn’s & Colitis Foundation of America.

At this year’s Annual Scientific Meeting of the American College of Gastroenterology (ACG) in Honolulu, researchers are discussing ways to improve both the diagnosis and treatment of these diseases.

Today, for instance, scientists are looking at how antibodies in a patient’s blood and urine can be used to differentiate these diseases. At ACG, researchers will discuss how symptoms outside the digestive tract can be used to tell these diseases apart.

With the proper diagnosis, doctors can then select the best treatment, from medical options—such as steroids, immunosuppressants and biologics—to more severe surgical procedures to remove diseased sections of the bowels. While up to 75 percent of ulcerative colitis patients will respond to medications, 70 percent of Crohn’s disease patients will undergo surgery.

Even the medical treatment options are far from ideal. “Steroids, immunosuppressants and biologics both have unattractive safety profiles, and patients often become less responsive to biologics over time,” Rossiter said.

New ways to treat inflammatory bowel diseases will of course also be a topic of conversation at ACG. Although medical and surgical treatment can help ease some of the symptoms, none targets the root causes. And there are no cures.

“We need something else to improve the quality of life of these patients,” Monteleone said. “These are nasty conditions that affect their lives; they stay home for long times, cannot work, cannot spend time with their relatives because of their quality of life and hospitalizations.”

Patients have reasons to be hopeful, though, as new treatment options are being developed. And the recent recognition of both Crohn’s and ulcerative colitis as orphan diseases by the U.S. Food and Drug Administration should help expedite the development of several therapies currently in clinical trials.

“We have a long way to go in terms of helping the most patients with medical therapies,” Aberra said. “We can get some patients into remission, but some do not respond at all; we still need to figure out which patients will respond to which medicine.”