Frailty Is a Risk Factor for Immunosuppression-related Infection in Inflammatory Bowel Disease

Immunosuppressive therapy is a cornerstone of effective management of inflammatory bowel disease (IBD). However, the possibility of infection is an important concern, and older age is one of the most consistently described risk factors.

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An important limitation of studies of older patients with IBD is that age has been defined chronologically. Bharati Kochar, MD, MSCR, gastroenterologist in the Division of Gastroenterology at Massachusetts General Hospital, Ashwin N. Ananthakrishnan, MD, MPH, director of the Mass General Crohn's and Colitis Center, and colleagues note that frailty, a well-established concept in geriatrics, helps stratify older population with respect to biologic reserve and functional status. In Gastroenterology, the team documents that pretreatment frailty, independent of age and comorbidities, is a novel risk factor for infectious complications of immunosuppressive IBD therapy.

Study Details

The researchers reviewed data on 11,001 patients with IBD who received care at Mass General or one of its partner hospitals between 1996 and 2010. Patients were classified as frail if at least one frailty-related diagnostic code was recorded within two years before the first prescription of an immunosuppressive agent.

Examples of frailty-related conditions are malnutrition, subacute delirium, difficulty with walking, dementia and urinary incontinence.

The primary outcome was the occurrence of an infection within the first year of starting a tumor necrosis factor (TNF) inhibitor or an immunomodulator (azathioprine, mercaptopurine or methotrexate).

Anti-TNF Group

There were 1,299 patients who were treated with a TNF inhibitor, usually infliximab (84%). Of those patients, 68 (5%) were classified as frail (8% of those ≥60 years old and 5% of those <60). In this group, they found:

• Frail patients were twice as likely as fit patients to develop an infection in the first year of starting a TNF inhibitor (19% vs. 9%; P = .01; OR, 2.32; 95% CI, 1.23–4.37)
• Higher risk of infections remained after adjustment for age, comorbidities and concomitant medications (aOR, 2.05)
• The risk of infection was similar in patients with Crohn's disease or ulcerative colitis

Immunomodulator Group

There were 2,676 patients who were treated with an immunomodulator, usually thiopurine (90%). Among them, 212 patients (8%) were classified as frail (12% of those ≥60 years old and 7% of those <60). In this group, they found:

• Frail patients were more than twice as likely as fit patients to develop an infection in the first year after immunomodulator initiation (17% vs. 7%; P < .01; OR, 2.59; 95% CI, 1.74–3.83)
• Higher risk of infections remained after adjustment for potential confounders (aOR, 1.81)

Applying the Findings to Practice

Previous studies have documented physicians' reluctance to consider systemic immunosuppression for older patients. However, rates of disease progression and the need for surgery in older patients with IBD are similar to or even higher than in younger patients.

Early and effective treatment of IBD is important in suitable older patients to prevent these morbidities. Frailty is an additional factor that can identify older patients who are good candidates for immunosuppressive therapy.

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