Very Few Older Adults Are Included in Trials of IBD Medications

Journal Published on June 17, 2021

Originally published on Inflammatory Bowel Diseases

Key findings

This systematic review examined the inclusion and analysis of older adults in 46 randomized, controlled trials of currently approved medications for inflammatory bowel disease (IBD) that were published in leading medical journals in 2000 or later
Only 26 IBD trial reports (57%) indicated whether older adults were included; of the 18 trials that were known to be open to older adults, only 62 of 6,831 patients (0.9%) were ≥65 years old
IBD trials of mesalamine agents had the highest proportion of older adults (5.7%) and trials of biologic agents had the lowest proportion (0.5%)
39% of IBD trials specified an upper age limit, 59% excluded patients with a history of cancer and 64% excluded patients with other comorbidities that disproportionately affect older adults
No IBD trial considered functional status as an inclusion or exclusion criterion or evaluated it as an outcome measure

The number of older adults with inflammatory bowel disease (IBD) is rising rapidly, especially in Western nations, because of more effective treatments for other diseases, improved life expectancy and the global increase in IBD incidence and prevalence. In the U.S., 26% of patients with IBD are ≥65 years old.

Older adults with IBD experience worse outcomes than younger patients; those with ulcerative colitis have a 57% higher rate of surgery and those with Crohn's disease have nearly six-fold greater IBD-specific mortality. These disparities may arise because, as in other disease states, older adults are underrepresented in clinical trials.

Bharati Kochar, MD, MSCR, a gastroenterologist in the Division of Gastroenterology at Massachusetts General Hospital, Nneka N. Ufere, MD, faculty of the Cancer Outcomes Research and Education Program in the Massachusetts General Hospital Cancer Center, Ashwin N. Ananthakrishnan, MD, MPH, director of the Crohn's and Colitis Center, Christine Seel Ritchie, MD, MSPH, director of research in the Division of Palliative Care and Geriatric Medicine and director of the Mongan Institute Center for Aging and Serious Illness, and colleagues were the first to assess the inclusion of older adults in the randomized, controlled trials (RCTs) that guide current IBD treatment. The lamentable results, reported in Inflammatory Bowel Diseases, make it clear that RCTs in IBD need to provide a much better representation of older adults.

Study Methods

In a systematic review, the researchers searched for published RCTs of currently approved IBD medications that were published in 2000 or after. To focus on studies most likely to affect routine clinical practice, they included only articles from eight leading medical journals, selected by impact factor:

General Medicine:

The New England Journal of Medicine
The Journal of the American Medical Association
Lancet
The BMJ (British Medical Journal)

Gastroenterology:

Gut
Gastroenterology
Clinical Gastroenterology and Hepatology
American Journal of Gastroenterology

After applying exclusion criteria, including excluding phase 1 and 2 trials, the team analyzed 23 RCTs in ulcerative colitis and 23 in Crohn's disease. There were four trials of mesalamine formulations, 13 of nonbiologic immunosuppressants and 29 of biologic agents.

Results

Only 26 of the 46 trial reports (57%) indicated whether older adults were included. A total of 18 trials were open to older adults, but of the 6,831 patients in those trials, only 62 (0.9%) were ≥65 years old.

The proportion of older adults was 5.7% in trials of mesalamine formulations, 1.2% in trials of nonbiologic immunosuppressants and 0.5% in trials of biologics. Only 11% of trials reported age-specific subgroup analyses. 39% of trials specified an upper age limit, 59% excluded patients with a history of cancer and 64% excluded patients with other comorbidities that disproportionately affect older adults.

No trial reports mentioned functional status as an inclusion or exclusion criterion, or evaluated functional outcomes.

A Vicious Cycle

Many researchers are reluctant to include older adults in IBD trials of immunosuppressants because of concerns about adverse events, and many clinicians are equally reluctant to use them to treat older IBD patients because of the lack of safety data—a vicious cycle. Now that biologics are becoming a mainstay of IBD treatment, thoughtful efforts to increase the representation of older adults in their trials will be essential.

Functional status is routinely considered in RCTs of cancer therapies to identify patients at greater risk of adverse events, and the same should be done in IBD trials. Making functional status a criterion for trial eligibility should actually expand the number of older adults represented.

0.9%

of participants in randomized controlled trials of IBD medications were ≥65 years old

0.5%

of participants in randomized controlled trials of biologics for IBD were ≥65 years old

64%

of randomized controlled trials of IBD medications excluded patients with nonmalignant comorbidities that disproportionately affect older adults

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Inflammatory Bowel Diseases

Journal Article Published: March 11, 2021

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Contributors

Ashwin N. Ananthakrishnan, MBBS, MPH ›

Director of the Crohn's and Colitis Center, Division of Gastroenterology, Mass General, Associate Professor of Medicine, Harvard Medical School

Bharati D. Kochar, MD, MSCR ›

Gastroenterologist, Division of Gastroenterology, Massachusetts General Hospital, Assistant Professor in Medicine, Harvard Medical School

Christine S. Ritchie, MD, MSPH ›

Director of Research, Division of Palliative Care and Geriatric Medicine, Massachusetts General Hospital, Director, Mongan Institute Center for Aging and Serious Illness, Massachusetts General Hospital, Professor of Medicine, Harvard Medical School

Nneka N. Ufere, MD, MSCE ›

Physician-Investigator, Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Assistant Professor of Medicine, Harvard Medical School

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