Imaging Can Help Guide Decisions and Outcomes in Perianal Crohn Disease

Advances in medical therapies for Crohn disease (CD) have improved outcomes for patients with this inflammatory bowel disease (IBD), but the durable healing rate for fistulas among patients with perianal CD remains disappointing, David Schwartz, MD, told the audience at the Advances in Inflammatory Bowel Diseases virtual regional meeting on June 19.

Dr Schwartz is director of the Inflammatory Bowel Disease Center and professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee.

In a study he conducted during the late 1990s, Dr Schwartz said, he found that an incidence of perianal fistulas of approximately 25% among patients with CD during the course of their disease. A more recent study conducted in Olmstead County, Minnesota, revealed an incidence rate of about 14.5% since 1998. “Perhaps one of the reasons for this is the increasing use of biologic therapy, which can act as a preventative against patients with Crohn’s disease from developing fistulas,” he noted.

“We know that the more distal the disease, the more likely the development of perianal fistulas,” Dr Schwartz stated. “In patients with rectal involvement there is a nearly 100% chance of developing a perianal fistula in the course of their lifetime.”

He pointed out that a retrospective study from Leiden of 232 pts with perianal fistulas and CD, over 10-year follow-up period, showed that 78% had complex fistulas and only 37% of these patients experienced long-term healing. “The data with simple fistulas was much better; nearly two-thirds of these patients experienced durable healing.” However, altogether some 53% of these patients required surgery, including proctectomy and colectomy. Further, Dr Schwartz pointed out, the most recent Mayo cohort showed a proctectomy rate of 19%, which is essentially unchanged since the 1990s.

Perianal Crohn disease is also the mostly costly manifestation of CD—more than double the cost of care for patients with Crohn disease without perianal fistulas.

The most important step in caring for patients with perianal CD, Dr Schwartz said, is a thorough initial assessment, including imaging studies to guide decision-making about the treatment. “The key to successful management is to establish adequate drainage of all abscesses and to control fistula healing. An imaging modality should provide a virtual road map for this purpose.”

A prospective triple blind study in 2001 compared the accuracy of assessments made by endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and examination under anesthesia (EUA) in patients with suspected perianal CD. “All 3 modalities showed excellent accuracy in assessment,” Dr Schwartz said. “The key take-home point is that combining EUA either imaging study can increase accuracy of assessment of perianal anatomy to 100%, which translates to better outcomes.”

Controlling fistula healing is very important in optimizing outcomes, he said. A study showed that patients who had setons placed prior to beginning biologic therapy had lower health care utilization, lower costs, and better outcomes than patients who received biologic therapy without the placement of setons.

“Why is examination under anesthesia important before beginning biologic therapy? The main reason is that the fistula track is effectively a tunnel from the inside to the outside that shouldn’t be there,” Dr Schwartz explained. The body wants to close off this opening, and for patients on biologics, this happens very quickly. Unless the fistula is adequately drained, this closure often causes recurrent fistula or abscess. “The job of the seton is to traverse that opening and allow that fistula to drain.”

In regard to medical therapy, antibiotics are widely used in the management of perianal CD. Dr Schwartz noted that in one randomized prospective study, the combination of adalimumab and ciprofloxacin achieved fistula healing among 71% of patients compared to a 47% healing rate among patients treated with adalimumab alone. However, when the antibiotic was discontinued at 12 weeks, the two arms showed similar rates of healing at 24 weeks.

“Because of this, I tend to use antibiotic therapy when I start biologics and keep patients on antibiotic therapy for quite a long time. Usually, I continue antibiotic therapy for a few weeks after I pull a seton, which is somewhere in the range of 3 to 6 months.”

Among other medical therapies, Dr Schwartz said, anti-tumor necrosis factor (TNF) agents “really revolutionized care for patients with perianal fistulas.” Studies showed response rates of 56-68% of patients on infliximab, although the fistulas recurred when medication was stopped. All 3 anti-TNFs approved for CD—infliximab, adalimumab, and certolizumab—have demonstrated fistula closure rates of 30% to 40%, he said. “That’s certainly much better than what we’ve had in the past, but we would like it to be much better. There are still about two-thirds of our patients not doing as optimally as we would like.”

The reason may be that patients are receiving too low a dose of anti-TNF, Dr Schwartz said, pointing out studies that have shown the need for higher trough levels of these agents to maximize outcomes in perianal disease, “much higher than what we use to treat luminal CD.”

In the future, Schwartz said, imaging will continue to be important in guiding therapy and helping to improve outcomes on many levels. Using MRI to guide dose escalation helped improve response in one study, he noted. Another study examined the impact of using EUS to do an initial assessment prior to placement of setons and followed by the use of an immunomodulator, anti-TNF, and antibiotics. This course was followed by reimaging with EUS to assess healing, and resulted in  long-term healing in more than three-quarters of the patients in one study.

In addition, Dr Schwartz said, 2 randomized studies compared the outcomes when EUS guidance was used to determine when to remove setons and when standard of care was used, with the surgeon making the decision without EUS. The healing rates at 6 months in these cases were 78% vs 27%, respectively.

One medical option that is being studied in Europe involves the use of adipose stem cell therapy, which involved curettage of the track, placement of setons, and then the closure of the fistula track and injection of adipose stem cells. The ADMIRE trial achieved healing rates of about 50% in “a very refractory, largely TNF-exposed population.”

Schwartz noted that for most gastroenterologists, “the vast majority of your patients with perianal Crohn’s disease will have a complex fistula.” He shared his own algorithm for maximizing outcomes for these patients. “Ask the surgeon to place a seton, and start therapy with immunomodulators, an anti-TNF, and antibiotics. In this patient population, I would definitely consider using imaging, probably MRI, to monitor fistula healing and maximize outcomes. In those who do not respond to medical therapies, I would check the anti-TNF trough level and maximize that.” For patients whose anti-TNF therapy is already maximized, Schwartz noted that there are data showing some efficacy in perianal fistula healing with vedolizumab and ustekinumab, and he uses tacrolimus as an adjuvant with some patients.

“Hopefully soon, we may be able to offer patients in the United States adipose stem cell therapy for perianal Crohn’s disease,” he stated.

--Rebecca Mashaw

Schwartz, DA. Perianal Crohn’s disease today and tomorrow. Presented at: Advances in Inflammatory Bowel Disease regional meeting. June 19, 2021. Virtual.