Why Rome IV Matters in Irritable Bowel Syndrome

The natural history of irritable bowel syndrome (IBS) defined according to the stricter Rome IV criteria is more severe than that of Rome III-defined IBS, a longitudinal study found.

This has important implications for patient selection in future treatment trials, according to the investigators, led by Alexander C. Ford, MD, of the Leeds Gastroenterology Institute in England.

As shown in the team’s 12-month follow-up study published online in Clinical Gastroenterology and Hepatology, patients with Rome IV-diagnosed IBS were significantly more likely than their Rome III-defined counterparts to have:

• Seen a primary care physician (44.7% vs 28.5%, P<0.001) or a gastroenterologist (26.3% vs 12.4%, P<0.001)
• Started a new treatment (73.0% vs 60.2%, P=0.001)
• Cycled through more treatments (e.g., for three treatments 14.8% vs 8.6%, P=0.007)

The more restrictive Rome IV criteria have been used since 2016 to diagnose IBS, a functional bowel disorder affecting an estimated 5-10% of the world’s population. “So trial recruitment may be more difficult as the criteria are more restrictive, so fewer people who think they have IBS meet Rome IV than Rome III criteria,” Ford told MedPage Today. “Also, if symptoms are more severe, that may affect power calculations and efficacy of drugs.”

Asked for her perspective, Elena A. Ivanina, DO, MPH, of Lenox Hill Hospital, Northwell Health, in New York City, who was not involved with the study, said: “This makes sense, as you are now describing a sicker cohort of patients with abdominal pain rather than just discomfort, and more frequent abdominal pain, and not other symptoms that could be misinterpreted as discomfort such as bloating.”

She called the findings helpful, since clinicians need more specific guidance on how to distinguish IBS from the other functional bowel disorders. “This will help guide treatment and management decisions and ensure that clinical trials maintain vigorous standards for identifying IBS patients and therefore have more meaningful outcomes in the era of precision medicine,” she told MedPage Today.

Study Details

During 2017-2018, the Leeds group collected baseline data on demographics, symptoms, mood, and psychological data from 1,097 adults registered in three British health-related organizations. All those included self-identified as having IBS and met either Rome IV or III criteria.

At 12 months, the researchers followed up with an online questionnaire to gather data on symptom severity and impact, medical consultation behavior, treatments commenced, and psychological health. The group then examined differences between subsequent disease behavior in those with Rome IV- versus Rome III-defined IBS.

At 12 months, 638 of the 1,097 participants (58.2%) were successfully followed up. At baseline, 452 of these respondents had met Rome IV criteria and 86, Rome III. Mean age in both IBS categories was about 50, with Rome IV participants being slightly younger (age 49 vs 53); in addition, more than 80% were women, and more than 95% were white.

At follow-up, individuals with Rome IV IBS also had more severe symptoms and experienced a significantly greater impact from IBS on activities of daily living and more often reported continuous abdominal pain. A higher proportion reported poor psychological health (P<0.001 for all analyses).

On the psychological comorbidity front, Rome IV IBS was associated with abnormal anxiety or depression scores and high levels of somatic symptom disorder reporting. When the analysis was restricted to individuals with normal depression scores at baseline, those with Rome IV IBS were significantly more likely to have developed borderline abnormal or abnormal depression scores at 12 months, the researchers said.

“These differences may have a deleterious impact on the natural history of IBS but, to our knowledge, there have been no studies conducting longitudinal follow-up to examine whether this is the case,” Ford and colleagues wrote.

In another difference, Rome IV IBS appeared to be more stable, with 70.6% of those affected still meeting diagnostic criteria versus 47.3% of their Rome III counterparts.

While previous research has explored the differences between individuals with the two sets of criteria, the studies have been cross-sectional and have restricted analysis to the characteristics of individuals rather than prognosis according to one definition versus another, Ford and co-authors explained. “This design limitation means that, unlike the present longitudinal follow-up study, they can only report associations, rather than examine the influence of the changes made in moving from the Rome III to the Rome IV criteria on the natural history of IBS.”

The team concluded that Rome IV criteria select a population more likely to seek healthcare and to have a worse disease prognosis in terms of future symptoms and new onset of psychological comorbidity. In addition, the researchers said, although the findings probably relate to the more severe symptoms at baseline in Rome IV patients, they may also be explained by the more restrictive nature of ROME IV criteria.

The biggest impact of the findings, said Ivanina, will likely come from having a more precisely defined research cohort. “In Rome III, the term ‘discomfort’ was misinterpreted by different patients and cultures,” she said. “By studying a more objectively described condition, this will help clarify the prevalence or symptom severity of IBS when evaluated from a global perspective to help patients around the world.”

The study’s main limitation, Ford noted, was that it was U.K.-based and relied on self-reporting, although all participants met Rome criteria and were registered as having IBS with three organizations. In addition, follow-up was short at only 12 months.