Although the number of Crohn’s disease patients in the VHA and TRICARE systems is relatively small, the notoriously complex disease provides large challenges for the physicians who treat it.
In fiscal year 2009, the Military Health System diagnosed about 17,800 individuals with Crohn’s disease out of a total 10.18 million beneficiaries, according to TRICARE. Similarly, the VHA has recorded approximately 14,000 patients with at least two outpatient diagnoses or one inpatient diagnosis of Crohn’s during the past two years. (Those numbers may be on the increase for the VA, according to an August 2009 report published in Digestive Diseases and Sciences. While Crohn’s generally is considered to be a disease that affects young people and adolescents, the last 30 years have seen a growing shift toward older patients in the VHA, according to that study.)
Crohn’s disease can be hard to diagnose and “very difficult to treat,” said Maj. Ganesh Veerappan, M.D., assistant chief of the Gastroenterology Clinic at Walter Reed Army Medical Center in Washington.
In fact, the VHA and the DoD don’t currently provide evidence-based clinical practice guidelines for the diagnosis and treatment of Crohn’s disease. Several U.S.-based organizations do, including the American College of Gastroenterology (ACG).
Available treatment guidelines, however, “point to controversial areas in need of future research, including: treatments to achieve long-term remission; the benefits and harms of step-up [prolonged use of steroids] versus top-down [early use of immunomodulators and biologics] treatment strategies; and further evidence on optimizing the use of biologic agents given that many patients’ disease can be managed with traditional treatments such as aminosalicylates, antibiotics, corticosteroids and immunomodulators,” wrote researchers with the Agency for Healthcare Research and Quality (AHRQ) in the Evidence-based Practice Center Systematic Review Protocol for the ongoing project, Comparative Effectiveness of Pharmacologic Therapies for the Management of Crohn’s Disease. In addition, “[h]ow Crohn’s disease medications should be combined is a subject of ongoing controversy and investigation,” they noted.
The AHRQ review will attempt to answer some of these questions by comparing “the effectiveness, safety and patient-reported measures of individual and combined therapies for Crohn’s disease, including aminosalicylates, corticosteroids, immunomodulators and biologics with regard to: (1) induction of Crohn’s disease remission; (2) maintenance of Crohn’s disease remission; (3) adverse effects; and (4) patient-reported measures after surgical resection,” explained the researchers.
A Lifelong Disease
Obviously, treatment can’t be put on hold until these controversies are settled, but, from obtaining an accurate diagnosis to determining the optimal drug regimen, Crohn’s disease can present significant challenges for both patients and clinicians. This complex autoimmune disorder of the gastrointestinal tract is “a lifelong disease” that cannot be cured through either medication or surgery, according to Veerappan.
Almost three-fourths of Crohn’s disease patients will have a relapsing-and-remitting disease course throughout their lifetime. Only 10 percent achieve long-term remission. That said, 55 to 65 percent of patients are in remission at any point following the first year of diagnosis, while 15 percent to 25 percent have mild disease, and 10 percent to 30 percent have moderate to severe disease. In general, achieving and maintaining remission “as best as possible” is the primary goal of treatment, Veerappan said.
Because Crohn’s disease patients tend to be relatively young and no cure is available, wellness should be a key part of that remission goal, said Judy Collins, MD, Section Chief for IG at the Portland VAMC. “The goal of treatment isn’t simply, for example, that the patient’s hematocrit is normal. We are aiming for good quality of life also. These young individuals are trying to get educated, establish relationships and start families. We need to help them achieve this health to be able to integrate as effective members of the military or other modes of employment, as well as to have these other things in life that we all strive to achieve.”
The first step in obtaining remission and wellness is an accurate diagnosis. “It’s important to be sure of the diagnosis – to make sure that other diseases are ruled out,” said Veerappan. Unfortunately, Crohn’s disease can mimic many other gastrointestinal symptoms, making it “very difficult to diagnose,” he added. “The diagnosis often takes up to a year to make.”
Symptoms that could indicate Crohn’s disease include bloody diarrhea or abdominal pain. “Once Crohn’s disease is suspected, patients need to be referred to a gastroenterologist so the appropriate diagnosis can be made,” he said.
Clinicians use a combination of information to make the correct diagnosis, said Veerappan. Diagnostic tools include clinical presentation, laboratory exams, endoscopies, colonoscopies, and computed tomography (CT) scans. Some of these tools carry their own risks, so clinicians need to “weigh those risks and benefits” when choosing diagnostic procedures, added Collins.
Crohn’s disease has several symptom levels of disease behavior: inflammatory, stricturing and penetrating. That symptom level affects the treatment goals and, consequently, the drug choice. For example, “some drugs, such as mesalamine [an aminosalicylate], are effective for the lining of the colon or small bowel,” Collins said. “However, the perforating type of disease usually requires immune-modulating drugs.”
Treatment Carries Significant Risks
Many of the drugs used to treat Crohn’s disease carry significant risks. For example, immune-modulating drugs (e.g., 6-mercaptopurine, azathioprine and methotrexate) present increased risks for infection. Other medications carry a risk of developing lymphoma, and Crohn’s disease in general is associated with an increased risk for colon cancer. Establishing clear treatment goals is “very important in assessing the risk/benefit equation and being able to achieve wellness goals,” said Collins.
Treatments also must be “tailored to that individual patient” due to “a multitude of factors,” said Collins. For example, “not everybody tolerates the drugs equally,” she explained.
Once a treatment protocol has been selected, patient compliance is essential to remission, said Collins. Clinicians should work with patients to ensure they “understand and buy into the treatment,” she said. “Most of these young patients look quite good. So it is hard for them to convince themselves, as well as people around them, that they are really ill. Getting them to accept ownership is critical for successful treatment and compliance.”
Crohn’s disease treatment needs to be consistent—at the appropriate dosage and at the appropriate duration to achieve the treatment effect, said Collins. This is true whether patients are being treated with first-line drugs such as mesalamine or a tumor necrosis factor blocker (e.g., adalimumab, infliximab).
However, “once patients start to feel better, sometimes they think they don’t need their medications,” said Collins. With that type of “stop-and- start” approach to compliance, “you may lose drug effectiveness,” she said. “Remission is so critical, and that [type of noncompliance] has the long-term disadvantage for increased risks down the line —potentially even requiring surgery for some of those individuals when otherwise they could have been treated medically.”
One factor that may impact patient compliance is the number of pills they take. For example, “[Mesalamine] often requires up to 12 pills a day to get adequate levels of the drug, and taking that many pills can sometimes be an issue.” Newer formulations of mesalamine such as Apriso and Lialda are delivered in a capsule one to four times a day, improving compliance among patients at Veerappan’s clinic.
Importance of Health Maintenance
Health maintenance also should be a significant focus in Crohn’s disease treatment—or any inflammatory bowel disease, said Collins. Preventive care includes getting vaccinations or bone-density scans for osteoporosis when indicated, she explained. In addition, clinicians should “make sure that patients’ vitamin levels are checked appropriately and do a good health maintenance exam on them at least annually,” said Veerappan.
A multitude of environmental and extrinsic factors feed into wellness and maximal health for Crohn’s disease patients. Managing these factors “is a critical piece of maximizing the patient’s remission and sense of wellness,” said Collins.
For example, diet is a significant issue for military personnel. “When they are out in the field, having access to a regular diet and trying to maintain a normal day/night cycle can be difficult,” she pointed out. “However, maintaining that schedule is important for good gut health, particularly when you’re trying to achieve a remission.”
Homelessness is another issue that can create treatment difficulties for veterans, said Collins. Successful treatment depends on the appropriate diet and medications, as well as being able to monitor patients so the treatment can be fine-tuned—and taking those steps is obviously a more difficult challenge when the patient is also homeless, she explained.
Stress also has the potential to inhibit wellness goals. No studies have proved that stress is a contributing factor in disease flare-ups, said Veerappan. “Patients may have an irritable bowel syndrome on top of their inflammatory bowel disease, and that may be the disease that has actually flared with stress,” he suggested. Indeed, stress as a contributing factor “remains controversial,” according to the ACG Guideline, Management of Crohn’s Disease in Adults.
However, “this disease is an imbalance of the gut immune system, and chronic stress can affect the immune system,” noted Collins. Further, several recent studies have indicated that psychological factors such as stress or post-traumatic stress disorder may exacerbate Crohn’s disease.
While conclusive proofs are lacking, the studies offer a learning opportunity for clinicians, according to Charles N. Bernstein, M.D., who coauthored one of the studies and is director of the University of Manitoba IBD Clinical and Research Centre at the University of Manitoba in Winnipeg, Manitoba, Canada.
“The take-away message is that we, as clinicians, need to address stress in our patients. We need to ask them about whether they are stressed; and how they are dealing with it; and if they need help dealing with it,” said Bernstein. “Stress (and more specifically a patient’s perception of stress) may or may not impact on inflammation, but will impact on how a patient perceives of their symptoms and how they deal with it.”
Both clinicians and patients also need to recognize the importance of smoking cessation, said Veerappan. “Patients who smoke can make treating the disease really challenging.” Smoking in Crohn’s disease patients is associated with increased incidence of relapse, the need for repeat surgery and the initiation of drug therapy, according to the National Digestive Diseases Information Clearinghouse. In addition, women who are current or former smokers experience these risks at a higher rate than men.
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen can exacerbate inflammatory bowel disease symptoms, said Veerappan. “Certain groups of patients with Crohn’s or ulcerative colitis do get worse when on these medications, so we generally counsel patients to avoid them if possible.”
When [military personnel] are out in the field, having access to a regular diet and trying to maintain a normal day/night cycle can be difficult. However, maintaining that schedule is important for good gut health, particularly when you’re trying to achieve a remission.”