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Supplements Importance of Selecting the Appropriate Therapy for Inflammatory Bowel Disease in the Managed Care E

Report: Impact of Inflammatory Bowel Disease

Sheila M. Wilhelm, PharmD, FCCP, BCPS
     Human tropomysins (hTMs) induce allergy- and autoimmune-related immune responses. Onuma et al examined the immune response against hTMs by muco-sal immunocytes in patients with UC, CD, and non-IBD-related diarrhea.28 The researchers reported that patients with UC and CD had a higher percentage of IgG-producing cells compared with controls. While the total number of IgG-producing cells was similar between the 2 groups, the percentage of immunocytes producing hTM5 antibodies was higher in patients with UC. The researchers reported that up to 75% of IgG-producing immunocytes produced the hTM5 antibody, while none of the patients with CD had hTM5 antibodies, which was a significant difference (P <.00001).28 It is this abnor-mal immune response that results in the characteristic inflammation of UC and CD.

Ulcerative Colitis

     Inflammation in UC starts in the colon, and it pro-gresses proximally from the rectum in a symmetrical, circumferential, and uninterrupted pattern that may advance until the entire length of the large intestine is affected.29,30 Ninety-five percent of patients with UC exhibit inflammation in the rectum, and inflammation is confined to the rectum in 25% of cases.29,31

     UC is characterized by ulceration, edema, and hem-orrhage in the colon with inflammation limited to the mucosa and submucosa.24,31 Histologically, UC is associated with polymorphonuclear leukocytes and mononuclear cells. In addition, patients may exhibit crypt abscesses, mucosal gland distortion, and depletion of goblet cells.31

     Patients with UC may have periods of active disease and remission; at any given time, 50% of patients are in remission, although 90% will have an intermittent clinical course.32

Crohn's Disease

     CD is characterized by focal, asymmetric, transmural inflammation of the small bowel and colon, as well as by discontinuous ulceration and full-thickness inflamma-tion of the bowel wall with unaffected areas interspersed with affected.9,29,33 The inflammation may result in super-ficial ulcerations, strictures, abscesses, and fistulas.24,31 Microscopic examination shows thickened submucosa, transmural inflammation, fissuring ulceration, and non-caseating granulomas.24 For 40% of patients who are affected, the disease is confined to the ileum and cecum; for 30% of patients, it is limited to the small intestine; and for 25% of patients, it is mainly in the colon.29

Disease Progression

     Most patients with CD experience remissions and flare-ups of varying durations; some patients may experi-ence remission for years that may be interrupted by years of relapse.34 The disease can extend or regress over time and may be active in the same region of the GI tract or affect a different region. While a change in affected region does not seem to occur frequently, disease severity can change dramatically over time. Louis et al reviewed medi-cal records for 297 patients with CD who received regular medical follow-up and noted that over 10 years, 45.9% of patients had a change in disease behavior, with the proportion of patients who experienced a change in disease location being significant (P <.001).35 The most prominent changes reported were in patients with non-stricturing, non-penetrating disease; of these patients, 27% developed strictures (P <.0001) and 29.4% developed penetrating disease (P <.0001).35 A Danish prospective population-based study, conducted by Vester-Andersen et al, followed 513 patients with either UC or CD for a minimum of 7 years; the study results showed that 28.7% of patients with UC experienced disease progression, and 23.9% and 16% of patients with CD had changes in disease localization and behavior, respectively.36

Clinical Presentation and Diagnosis

     There is a lack of standard criteria for diagnosing IBD, and the conditions are often misclassified.37 The differen-tial diagnosis of UC and CD includes any infection- or ischemia-related diarrhea, medication-induced diarrhea, celiac disease, microscopic colitis, and irritable bowel syndrome.9 A medical history that includes recent antibiotic use, travel, or abdominal pain that is relieved with bowel movement may indicate causes other than IBD.38

     The signs and symptoms of UC and CD are similar. Patients with UC may present with persistent rectal urgency, bloody diarrhea, or tenesmus, and patients should undergo stool examination, sigmoidoscopy or colonoscopy, and biopsy to exclude infectious and non-infectious causes and confirm colitis.30 UC is typically diagnosed based on the presence of blood and mucus in the stool, as well as cramping of the lower abdomen that is more intense during bowel movements. The pain associated with UC is often located in the lower left quadrant of the abdomen with distal disease, and may extend to the entire abdominal region with pancolitis.31

     Due to the subtle presentation of symptoms, the diagnosis of CD is often delayed.31 Patients with CD experience abdominal pain, chronic or nocturnal diarrhea, rectal bleeding, weight loss, fever, and fatigue.9,39 If there is ileocolonic involvement, patients may report pain in the periumbilical area after eating.31 Gastroduodenal involvement may result in nausea, emesis, epigastric pain, early satiety, or dysphagia, whereas small bowel involvement may cause abdominal pain, anorexia, diarrhea, and weight loss.31 The diagnosis of CD is confirmed based on the findings from an upper or lower endoscopic evaluation, which allows identifica-tion of areas affected by disease and collection of tissue samples for pathological evaluation.9,38

     After 30 years of disease, up to one-third  of patients with UC will require surgery.40 Absolute indications for surgery include massive hemorrhage, perforation, and documented carcinoma; however, the most common indications for surgery are chronic symptoms, symptoms refractory to maximal medical therapy, physical debility, psychosocial dysfunction, and the inability to tolerate the adverse effects of medications.30 Surgical options typically include total proctocolectomy with either a permanent ileostomy or an ileal pouch-anal anastomosis, which results in the surgical construction of a pouch and new rectum to restore GI tract continuity without the need for an ileostomy.30 Vester-Andersen et al reported that 35 of 300 patients with UC underwent a colectomy for a 12.5% cumulative risk (95% CI, 8.8-17.6) at 7 years; also, 5 patients underwent perianal surgery.36 The median time to colectomy was 235 days (interquartile range [IQR]: 36-784 days), and the median time to perianal surgery was 796 days (IQR: 518-870 days).36

Approximately 70% of patients with Crohn’s disease eventually require surgery, and 30% of these patients will experience recurrence within 3 years.40 Surgical rates for patients with CD range from 30% to just over 60%.35,41 Location of disease appears to affect the risk of surgery with small bowel and ileocecal disease placing the patient at higher risk.41 The risk for surgery may be reduced by treatment with biologic therapy; however, these agents should be given early in the course of the disease.42 Vester-Andersen et al reported that 62 of 213 patients with CD underwent resection, with the cumulative risk of first resection of 28.5% (95% CI, 18.0-42.0); the cumulative risk of a second resection 5 years after the first was 29.0%.36 Additionally, 10.3% of patients underwent perianal surgery, with a median time to surgery of 453 days (IQR: 60-1036 days).36

     Data show a slight increase in mortality among patients with IBD compared with the general population. One study reported that although patients with UC do not have a greater risk of mortality compared with the general population, older age at diagnosis (>50 years), male gender, and extent of disease have shown some association with diminished survival.43 The results of a meta-analysis of 35 studies showed a small increase in all-cause mortality for patients with UC and the following comorbid conditions: colorectal cancer, pulmonary disease, and nonalcoholic liver disease. The mortality rates due to pulmonary disease and nonalcoholic liver disease were elevated for patients with CD.44 Another meta-analysis of 13 studies showed a 50% higher mortality risk for patients with CD compared with the general population.45

     In some cases, patients with IBD may experience non-GI related symptoms. Approximately 40% of patients with IBD experience low-grade, chronic fevers.31 Additionally, patients with CD may experience inflammation in loca-tions other than the intestines, which may result in joint pain or soreness, eye irritation, and skin changes.9,40 Prior to experiencing GI manifestations, patients with either UC and CD may sometimes have arthralgias and arthritis; however, these are usually associated with disease activity and improve when the underlying intestinal inflammation is treated.31

Impact of IBD on Quality of Life and Healthcare Costs

     IBD often manifests in young adulthood, and the relentlessness of the illness often affects a patient’s perception, body image, and quality of life (QoL).46 Studies have shown that QoL worsens in association with disease severity; patients with active disease have lower QoL scores compared with patients in remission.47-49 Patients with IBD have higher levels of psychiatric distress, anxiety, alexithymia, and somatosensory amplification; also, the inability to participate in social activities and the impact on relationships with friends, family members, and intimate partners contribute to lower QoL scores, as patients feel they have lower levels of social support compared with healthy people.50-52 In addition to the patient, their family members and loved ones are also affected.52

     UC and CD also have a significant impact on the healthcare system. Annual direct medical costs in the United States were reported in a 2008 analysis of data from 2003 to 2004 to be $2.1 billion for UC and $3.6 billion for CD.53 The annual costs per patient for UC are estimated at $7948 compared with $2715 for patients without IBD; 27.5% of UC costs are attributable to pharmaceutical claims, 34.9% to outpatient services, and 42% to hospital services. For CD, the annual cost per patient is estimated at $10,952 compared with $2898 for patients without IBD. Similar to UC, 35.3% of CD costs are for pharmaceutical claims, 33.3% for outpatient services, and 31.4% for hospital costs.53

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