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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

Inflammatory bowel disease (IBD) includes ulcer-ative colitis (UC) and Crohn’s disease (CD), 2 conditions characterized by chronic inflammation. Approximately 1.17 million people in the United States are affected by these 2 conditions. It is theorized that a genetic susceptibility coupled with environmental factors, such as smoking, antibiotics, oral contraceptives, appendectomy, or diet, may influence the development of IBD. Patients with UC and CD may exhibit similar symptoms, and the conditions are often misclassified, as there is a lack of standard criteria for diagnosing IBD. Therefore, it is important for clinicians to rule out any diarrhea-related conditions for an accurate diagnosis. UC and CD typically manifest in early adulthood, and the chronic nature of these conditions greatly impacts a patient’s perception, body image, and quality of life. The inability to participate in social activities due to UC and CD impacts not only patients, but also those with whom they have close relationships.
Am J Manag Care. 2016;22:S32-S38

Impact of Inflammatory Bowel Disease (Ulcerative Colitis and Crohn’s Disease)

     Inflammatory bowel disease (IBD) is characterized by chronic or recurring immune response in which the body mistakes food, bacteria, and other materials as foreign substances and attacks intestinal cells resulting in inflam-mation.1 The 2 most common IBD conditions are ulcer-ative colitis (UC), in which inflammation affects only the large intestine, and Crohn’s disease (CD), in which the entire gastrointestinal (GI) tract is affected.1


     Based on a 2013 analysis, it is estimated that approxiC -mately 1.17 million people in the United States have IBD.2 Since World War II, these numbers have changed slightly, and studies have shown that the incidence of IBD rose between 1940 and 1970, and then remained stable until 1990.3,4 However, since 1991, the incidence has risen approximately 7% for UC and approximately 31% for CD.5

The overall prevalence of UC is estimated to be 263 per 100,000 US adults with an estimated 593,000 Americans afflicted with the condition.2 The prevalence of UC increases with age, and while some studies report no gender differences evident in either children or adults, others show slightly higher prevalence rates in males.2,6

     It has been observed that UC typically manifests in patients between the ages of 30 and 40 years, with higher incidence rates reported in women between the ages of 30 and 60 and in women who resided in northern latitudes.2,7,8

    With an estimated 241 per 100,000 adults, or an estimated 565,000 Americans diagnosed with CD, the prevalence of CD in the United States is similar to that of UC.2 It has been observed that CD affects those in all age groups; how-ever, it typically manifests in the second and third decades of life (Figure 12).7,9 While the prevalence of CD increases with age, rates stabilize between the ages of 30 to 50.2 The prevalence of CD is lower in females and higher in male pediatric patients; however, in adult patients, the highest prevalence rates are in women between the ages of 30 and 60.2,9 Similar to UC, CD occurs more often in women who resided in the north than in the south.2

Risk Factors

     It is theorized that a genetic susceptibility coupled with any number of unknown environmental factors can trigger IBD. The condition is then sustained by an abnormal immune response, which leads to the disrup-tion of the intestinal mucosa and the underlying layers.10 The exact trigger factors for IBD are unknown; however, studies suggest that genetics, smoking, antibiotics, oral contraceptives, appendectomy, and diet may influence the development of IBD.


     It has been reported that patients with a first-degree relative with either UC or CD have a 10-fold increased risk of developing IBD compared with the general population.11 A similar increase in risk was also seen in patients with a second-degree relative affected; however, this risk was lower.11 A study examining perinatal risk factors and the development of IBD showed a significant increased risk of a child developing CD if the mother had CD (P = .011), if the mother was over 35 years (compared with younger than 35 [OR, 4.81; 95% CI, 2.32-9.98]), and if the mother smoked (compared with nonsmokers [OR, 2.04; 95% CI, 1.06-3.92]).12 No association was found between the perinatal risk fac-tors examined and the development of UC.12


     A relationship between smoking and the development of IBD has been demonstrated, and it has been reported that the risk of developing CD is 1.3 times greater in men and 5 times greater in women who are current smokers compared with people who have never smoked.13 Smoking appears to have a different effect on the development of UC. Compared with people who have never smoked, for-mer smokers have a 60% higher risk of developing UC.13 This may be due to an acute reduction in colonic mucus production following smoking cessation that may increase susceptibility to inflammation and the development of UC. Subjects who quit smoking more remotely have a similar risk of UC to those who never smoked. Additionally, the risk of UC is the same or slightly lower when comparing current smokers with people who have never smoked. Early childhood exposure to passive smoking was also asso-ciated with an increased risk of developing CD; however, this was not seen with UC.13 The differing effect of smoking in the development of UC and CD was also seen when tak-ing genetics into account. A study of 339 pairs of siblings, in which the pairs were discordant for both smoking and IBD phenotype (UC or CD), showed that smoking increased the risk for the development of CD, but appeared to have a protective effect on developing UC.14

Antibiotic Use

     A strong association between antibiotic use in the first year of life and the development of pediatric IBD has been reported.15 In addition, the increased risk was more frequently observed in males than females, and CD occurred more frequently than UC. This increased risk has also been noted in adult patients. Logistic regression was used to evaluate the link between antibiotic use and the development of CD; the results showed a statistically significant association between CD and antibiotic use 2 to 5 years prior to diagnosis (OR, 1.32; 95% CI, 1.05-1.65). The greatest increases in risk were observed with tetracy-cline (OR, 1.33; 95% CI, 1.01-1.77) and metronidazole and tinidazole (OR, 1.71; 95% CI, 1.05-2.76).16


     The use of oral contraceptives appears to have an impact on the development of IBD. For women currently using oral contraceptives, the age-adjusted hazard ratio (HR) for CD is reported to be 2.88 (95% CI, 1.69-4.89) and for past users 1.50 (95% CI, 1.13-1.99) compared with women who have never used oral contraceptives.17 In addition, current and past users of oral contraceptives had a higher, though not significantly, rate of developing UC compared with women who never used oral contraceptives. The HR was 1.22 (95% CI, 0.74-2.07) for current users, and 1.18 (95% CI, 0.91-1.52) for past users.17


     It has been postulated that an appendectomy confers a protective effect against the development of UC. A cohort of 212,963 patients from the Swedish Inpatient Register showed that patients who underwent an appendectomy had a significantly lower incidence of UC com-pared with controls (incidence rate ratio [IRR], 0.74; 95% CI, 0.64-0.86).18 However, multivariate analysis showed that the incidence of UC was low in patients who under-went an appendectomy for inflammatory conditions (ie, appendicitis, lymphadenitis) compared with controls, but no different from controls among patients who under-went an appendectomy for nonspecific abdominal pain, which suggests that the inflammatory condition is related to the development of UC, not the appendectomy. The opposite was seen in patients with CD. The increased risk of CD and disease severity was related to the under-lying diagnosis. Patients with perforated appendicitis had a higher IRR (2.11; 95% CI, 1.21-3.79) and more aggressive disease. The incidence risk was similar for other diagno-ses but patients had less aggressive disease.19


     Reif et al reported that an examination of pre-illness diets of patients with UC and CD showed a relationship between sucrose consumption and illness development.20 The researchers state that high sucrose consumption is often associated with a high consumption of processed foods and decreased consumption of fruits and vegetables, the interplay of which may contribute to the diseases. Additional studies have demonstrated a rela-tionship between fiber, dietary fat, and possibly protein with the development of IBD. The Nurses’ Health Study is a prospective cohort of 121,700 women who were followed for more than 26 years. Analysis of data from this cohort showed that long-term intake of dietary fiber was associated with a significantly lower risk of developing CD (HR, 0.59; 95% CI, 0.39-0.90); however, the same association was not seen for UC (HR, 0.82; 95% CI, 0.58-1.17).21 Results of an analysis of dietary fat intake in the same study population showed that high intake of dietary long-chain n-3 polyunsaturated fatty acids was associated with a reduced risk of UC (HR, 0.72; 95% CI, 0.51-1.01), while high intake of trans-unsaturated fats was associ-ated with an increased risk of UC (HR, 1.34; 95% CI, 0.94-1.92).22 A study of middle-aged women (40-65 years) reported that high protein intake, specifically high intake of animal protein, was associated with a significantly increased risk of IBD (HR for third vs first tertile, 2.63; 95% CI, 1.23-5.59 [P-trend = .008]).23

Disease Course

     It is theorized that the development of IBD is the result of a disproportionate and chronic inflammatory response to microbes in a genetically susceptible host.24 Animal studies showed that exposure to a single patho-gen can trigger an abnormal immune response.25 The characteristic signs and symptoms of UC and CD stem from a cytokine-driven, noninfectious inflammation of the gut. UC appears to be a Th2 cytokine-mediated disease, which is characterized by an increase in inter-leukin-5; CD is Th1 cytokine-mediated and results in an increase in interferon-γ.26,27

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