Inflammatory Bowel Disease: Nuances of Drug Therapy in Seniors and the Role of Vitamin D

US Pharm. 2013;38(12):18-20.

In the United States, gastrointestinal disorders in geriatric patients account for a significant portion of clinician visits, inpatient hospitalizations, and healthcare expenditures.¹ Inflammatory bowel disease (IBD), a group of debilitating conditions of which the vast majority of cases are composed of ulcerative colitis (UC) and Crohn’s disease (CD), is found with increasing frequency in the elderly. This may be partially attributed to an increasing number of IBD patients currently living into old age.² This article will review treatment issues and briefly discuss the relevance of vitamin D in IBD.  

IBD affects up to 0.5% of the population in developed countries and an increasing proportion in developing nations.^3-5 These conditions are most prevalent in Western countries and in areas of northern latitude.^6,7 For example, the incidence and prevalence of IBD are higher in northern Europe, North America, Australia, and New Zealand than in Asia.^3,4,8,9 Along those lines, the incidence of IBD in the Indian subcontinent is low; however, migrants to developed countries located at northern latitudes have a greatly increased risk of IBD.¹⁰ Furthermore, the onset of UC and exacerbations of CD are noted to peak in winter months in the Northern Hemisphere.^11,12 The highest reported prevalence rates of IBD are in Scandinavia, Great Britain, and North America.^6,7 The physiological activity of vitamin D is thought to be related to these observations. (See below, Vitamin D Deficiency in IBD.)  

Although IBD affects both genders equally, some studies indicate that more women suffer from CD, whereas more males suffer from UC.⁷ While onset of IBD is more common in early adulthood, epidemiologic evidence suggests a bimodal distribution of the age of onset of both UC and CD; peak incidence occurs in the second and third decades and a late-onset minor peak between 60 and 80 years.^1,13-15 Notably in the elderly population, there are challenges in diagnosis of gastrointestinal (GI) disorders that go beyond those of other patients. These include 1) comorbid illnesses such as dementia and depression that may impair communication between the patient and the caregiver; 2) medications, such that therapeutic and adverse effects may cloud the clinical picture in seniors, in whom polypharmacy is common; and 3) intestinal symptoms in the elderly that may be manifestations of other diseases.¹  

Etiology, Underlying Pathogenesis, and Complications

While the exact etiology of UC and CD is not known, both conditions are believed to be caused by similar factors. Infectious factors such as viruses (e.g., in measles), protozoans, mycobacteria (e.g., Mycobacterium paratuberculosis), and other bacteria (e.g., Chlamydia trachomatis, Escherichia coli) are all suspect agents.^16,17 Genetic factors also predispose patients to IBD, especially to CD. Characterized by a tendency for immune activation—both autoimmune and nonautoimmune—and inflammation, IBD is associated with a dysregulated mucosal immune response to intestinal microorganisms in a genetically susceptible host.¹⁸

In addition to intestinal complications, the IBD patient is at increased risk of systemic immune-related phenomena such as arthritis, nutritional deficiencies related to malabsorption of vitamin B₁₂ and folic acid, anemia secondary to blood loss from the GI tract, and bone disease, of which osteoporosis and fractures are of particular concern.¹⁸ While psychological factors (e.g., stress, emotional or physical trauma) are thought overall not to be an etiological factor, changes in mental health appear to potentially correlate with remissions and exacerbations, particularly with regard to UC.¹⁵  

Ongoing Inflammation: Risk of Colon Cancer

In patients with long-standing IBD, the risk of colon cancer is a significant complication that appears to be related to the degree of ongoing inflammation.¹ Risk increases substantially after 8 to 10 years of disease; when appropriate, surveillance for colon cancer includes annual colonoscopy with random mucosal biopsies for observation of early or advanced dysplasia.¹

Treatment  

The goals of treatment of IBD are 1) resolution of acute inflammation and complications, such as fistulas or abscesses; 2) alleviation of systemic manifestations like arthritis; 3) maintenance of remission; and 4) in certain cases, palliation or cure with surgery.¹⁵ Although the evaluation of IBD severity is difficult due to the largely subjective nature of the assessment, more objective measures, disease rating scales, and indices have been developed, including those that assess quality of life (see Reference 15). Selected agents used in treating IBD can be found in TABLE 1. Of note, there is a considerable difference between the goals of, and approach to treatment for, UC and CD; for detailed discussions of IBD medication therapy, including algorithm treatment approaches and specific dosing guidelines, consult References 15 and 19. In order to treat these diseases properly, realistic therapeutic goals for each individual must be conceptualized by the clinician and ideally should include collaboration with the patient to address issues including quality of life and medication (TABLE 1) risks versus benefits.

 

Selected Tips Regarding Drug Therapy in the Elderly

Intolerance of drug therapy often limits the usefulness of drugs that treat IBD. Adverse effects may be significant in some cases, thus requiring discontinuation of the therapy. Some of the nuances of IBD therapy are discussed below, focusing on the elderly, to encourage the tailoring of the medication regimen to the individual in conjunction with ongoing assessment (e.g., history and physical), close monitoring (e.g., selected laboratory tests), and evaluation of therapeutic outcomes.  

Avoiding NSAIDs: Reports have indicated that NSAIDs may trigger IBD occurrence or trigger exacerbation of underlying IBD; if possible, their use should be avoided.^15,20,21 The mechanism by which this occurs is thought to be inhibition of prostaglandin production via cyclooxygenase inhibition that may impair mucosal barrier protection. If the benefit of treatment (e.g., of patients with symptomatic arthritis) outweighs the potential risk of IBD flare, the use of NSAIDs may be warranted in some patients.²¹ Of note, the elderly are a high-risk population for adverse effects from NSAIDs; up to 60% of elderly people can develop peptic ulceration and/or hemorrhage asymptomatically.¹⁹  

Sulfasalazine: Unlike other sulfonamides, sulfasalazine is not absorbed when administered orally or as a suppository and is, therefore, reserved for the treatment of chronic IBD. Of note, it is intestinal flora that split sulfasalazine into two components: 5-aminosalicylate, which exerts an anti-inflammatory effect, and sulfapyridine, which can lead to toxicity in patients who are slow acetylators, whereby it precipitates at neutral or acidic pH, causing crystaluria (stone formation).²² Nephrotoxicity may develop secondary to crystaluria; preventing this adverse effect requires adequate hydration and alkalinization of urine.²² Patients receiving sulfasalazine should receive oral folic acid supplementation to prevent anemia secondary to malabsorption.¹⁵

Transient warfarin potentiation occurs with concomitant sulfasalazine use owing to displacement of warfarin from binding sites on serum albumin; free methotrexate levels may be increased because of displacement as well.²² Other potential problems associated with sulfasalazine are hypersensitivity reactions such as rashes, angioedema, and Stevens-Johnson syndrome; in order to direct appropriate therapy, it is of paramount importance to investigate a report of a previous sulfa allergy with regard to a description of the reaction.^22,23 Granulocytopenia, thrombocytopenia, and hemolytic anemia (i.e., in patients with glucose 6-phosphate dehydrogenase deficiency) can occur.²² Since sulfonamides condense with formaldehyde, sulfasalazine is contraindicated in patients who receive methenamine for urinary tract infections.²²

Mesalamine: Approximately 80% to 90% of patients who are intolerant to sulfasalazine’s adverse effects will tolerate oral mesalamine derivatives.²⁴ With regard to rectal suppositories, the elderly may have difficulty administering and retaining this dosage form.¹⁹ In light of age-related renal function decline, serum creatinine should be monitored often during therapy.¹⁹  

Corticosteroids: While systemic corticosteroids are effective in moderate-to-severe active UC and CD, high doses must often be used for extended periods; thus, their use confers a higher risk of complications in the elderly, including accelerated bone loss and fractures, hypertension, and glucose intolerance.^1,15 Use of systemic corticosteroids in geriatric patients should involve the lowest possible dosage, and for the shortest possible time. For long-term use, bone mineral density should be monitored and fracture prevention strategies should be instituted (TABLE 2).^19,25 Corticosteroids are not effective as maintenance treatment in either UC or CD.¹⁵  

Immunomodulator and Immunosuppressive Agents: These drugs are associated with an increased risk for toxicity in the elderly. Recommended dosages should be reduced when initiating therapy in geriatric patients because of possible decreased metabolism, reduced renal function, and presence of comorbidity-drug interactions and drug-drug interactions.¹⁹

Biological Agents: All tumor necrosis factor alpha (TNF-α) inhibitors predispose patients to development of serious infections; studies indicated that the elderly have an increased incidence of infection and malignancy compared to younger adults under 65 years of age.¹⁹ The use of natalizumab, a novel biological agent, is associated with the development of progressive multifocal leukoencephalopathy.²⁶ In light of the higher incidence of infections and malignancies in the geriatric population, caution and close monitoring are advised when these agents are used in the elderly.¹⁹ In addition, elderly patients with a history of heart failure may be at risk for exacerbation. Infliximab is contraindicated for individuals with New York Heart Association (NYHA) Class III-IV heart failure; caution is advised in those with congestive hear failure or NYHA Class I-II.^19,26

Vitamin D Deficiency in IBD

Vitamin D deficiency is more common in adults and children with IBD (especially CD), as compared with healthy controls, and correlates with a poorer health-related quality of life.^27-32 Factors such as malabsorption (i.e., secondary to mucosal disease or surgical resection) and reduced sunlight exposure, physical activity, and dietary intake are likely to contribute to this finding.¹⁸ While not specifically studied in patients with IBD, it is thought that an active inflammatory state may cause a reduction in total 25(OH)D₃ levels, owing to reduced hepatic production of vitamin D–binding protein.³³ Garg and colleagues point out that the relationship between IBD and the vitamin D axis appears to be a multi-faceted one involving the ongoing maintenance of musculoskeletal health (TABLE 2) and possibly the control of disease-related activity via immunomodulation, and modification of the risk of IBD-associated malignancy.¹⁸ A review of the role of vitamin D in bone health, immune regulation, and cancer prevention in IBD is available at www.medscape.com/viewarticle/767843.

Conclusion

While onset of IBD is common in young adults, it also is found with increasing frequency in the elderly. Currently, there is a greater and better variety of agents to treat patients with IBD for both acute conditions and remission maintenance. Medication regimens for senior IBD patients, based on the nuances of these therapies, require careful and appropriate geriatric dosing, monitoring, and ongoing assessment.

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