Michael Snyder, MD, on Fistulizing Crohn Disease

Involving the gastroenterologist, colorectal surgeon, and other health care providers as needed is essential in the appropriate and effective treatment of fistulizing Crohn disease (CD), Michael Snyder, MD, told the audience at the Advances in Inflammatory Bowel Diseases virtual regional meeting on August 27.

“I talk daily to my GI colleagues to make sure we do the right thing for each of these patients, so we can improve their morbidity and allow their quality of life to be as good as we can possibly make it,” he stated.

Dr Snyder is the program director for Colon and Rectal Surgery at the McGovern School of Medicine at UT Health in Houston, Texas.

He explained that of the half million Americans with CD, 10% initially present with anal disease and 25% will ultimately develop anal fistulae. Fistulizing disease is a risk factor for poor outcomes, significant morbidity and reduced quality of life, Dr Snyder said, with 70% of these patients eventually requiring surgery.

“The quality of evidence for treatment of fistulizing Crohn’s disease is sorely lacking, due to the lack of randomized control trials,” he added.

Fistulae resulting from perianal CD may present as simple cryptoglandular infection, he said. However, approximately 80% of Crohn fistulae are complex. “Proctitis has an adverse effect on fistula healing and increases the risk of recurrence, while acute suppuration mandates control of the infection prior to any evaluation or additional treatment,” Dr Snyder explained.

Because many patients with fistulizing CD are young adults who are not accustomed to seeking medical care for a complex condition, “there is often a significant delay between the onset of symptoms and consultation for medical care,” he continued. Complicating this situation is the fact that the cost of care may be very high, as younger patients often have high deductible and disease-limiting plans.

“The current treatment paradigm for fistulizing Crohn’s is to control the infection; study the fistula to determine how best to treat it; identify other intestinal and extraintestinal manifestations of Crohn’s; institute medical therapy; and then do surgical intervention to close the fistula,” Dr Snyder said.

Magnetic resonance imaging (MRI) “is the ‘gold standard’ for diagnosing and determining the extent of a Crohn’s perianal fistula, but there is only low-quality evidence of the real utility of MRIs,” he stated. Observational studies suggest MRI correctly classifies fistulae 90% of the time and is useful in determining healing with anti-TNF therapy. However, MRIs are costly, and the long-term use of MRI appears more problematic as its ability to confirm healing after cessation of therapy ranges from 50%-90%.

Endoscopic ultrasound (EUS) offers some advantages in imaging for fistulizing CD. “It’s operator-dependent; much less costly than MRI; it’s easy to do serial exams; and it can be an in-office procedure,” Dr Snyder explained. “In some small randomized controlled trials, using EUS to guide medical and surgical therapy was associated with accelerated medical treatment and fistula resolution.”

He noted: “Both modalities have their advantages; they’re not one or the other. Oftentimes I’ve gotten an MRI to see what the fistula currently looks like, and I get EUS to see how the fistula evolves over time.”

Medical management is an essential element in fistulizing CD, he stated. “In the case of simple fistulae, in the rare case where neither proctitis nor luminal disease exists, then we drain the abscess, place the setons, use antibiotics, and then eventual fistulotomy are sufficient.”

Unfortunately, these cases are rare, he said. “The majority of fistulae from Crohn’s disease are technically complex and a top-down approach appears to be associated with faster and more durable resolution.” This approach consists of initial anti-TNF therapy in combination with antibiotics and fistula control through placement of a noncutting seton. The addition of thiopurines appears beneficial for resolution of proctitis, softening of rectal mucosa, and eventual resolution of the fistula through surgery, Dr Snyder explained.

Randomized trials have demonstrated 62% response and 46% complete remission among patients with fistulizing CD treated with infliximab. However, he pointed out, infliximab “is a mouse-human chimeric antibody, so the develop of antibodies has always been an issue.”

Maintenance is needed to preserve the initial response to therapy, but even then, loss of response tends to occur at about 1 year. The ACCENT II trial demonstrated a 36% rate of fistula healing long-term, Dr Snyder said.

In the SONIC trial and a retrospective European study, researchers found that combination therapy with thiopurines appears to improve the durability of infliximab response, he stated. “

The addition of antibiotics trends towards improving fistula healing, but there is no strong evidence to support this observation, despite its inclusion in several guidelines.”

Adalimumab is a fully humanized antibody, Dr Snyder stated, which shows efficacy in fistula healing in some studies, “but the quality of data is moderate due to the limitations of subgroup analysis. The addition of antibiotics appears to improve efficacy and the CHARM trial in 2007 demonstrated 90% durability of fistula healing.”

Surgical management of fistulae is “somewhat straightforward but not as successful as we’d like it to be,” he explained.

The first step is to drain perianal abscesses prior to initiating immunosuppressive therapy. “We usually place setons at the time of drainage, and use noncutting setons to minimize incontinence,” Dr Snyder stated. “This helps reduce infection and inflammation. Patients feel better; the infection goes away and the rectal tissue surrounding becomes softer.”

In combination with anti-TNF therapy, placing setons improves response to medical therapy and lowers recurrence of the fistula, according to the results of some studies, he explained, although the quality of data is moderate.

The timing of seton removal is not well defined, Dr Snyder said. “The consensus, and my own practice, is to remove the seton after both induction with anti-TNF agent and resolution of proctitis. You have to have resolution of the proctitis to have nice soft rectal mucosa before you attempt this, otherwise you have a very high failure rate,” he stressed. “My personal experience is that about 30% of patients, long-term, can be managed with removal of the seton alone.”

Closure of the fistula tract can be surgically managed in different ways, Dr Snyder explained. “A fistulotomy is okay with a simple fistula but it should be avoided with more complex disease, due to high incidence of incontinence and the likelihood of other fistulae forming in the future.”

Dr Snyder has seen a success rate of 60% to 70% with the advancement flap procedure among patients without proctitis in his own practice. There are poor data to support placement of fistula plugs, although one study suggested it has similar efficacy to just removing the seton. Dr Snyder said he no longer places plugs.

The ligation of intersphincteric fistula tract (LIFT) procedure involves dissection in the tract, followed by fistula division and ligation of both ends of the tract, he explained. “Tracts in Crohn’s disease are often wider than in cryptoglandular fistulae, so they are more technically challenging. Tracts that are relatively narrow are very amenable to this process, but Dr Snyder does not perform the LIFT on very wide CD tracts, he said. Two retrospective studies show an approximate 48% rate of fistula healing with LIFT, with most recurrences in the first year.

The most recent advance in the treatment of fistulizing CD is the use of mesenchymal stem cells, successful in producing remission in a little over half of patients, Dr Snyder stated.

These cells can be harvested and cultured from adipose tissue and may be directly injected or attached to fibrin glue or a plug scaffold. “Several trials have confirmed the safety and efficacy of stem cell therapy in managing fistulizing Crohn’s disease,” he said, including a study by Lightner et al that demonstrated using stem cells with a carrier, such as fibrin glue or a plug, was more successful than injection.

“Optimal delivery is still in evolution,” Dr Snyder said, “but this therapy is definitely a bright light for our treatment modalities.”

“The ultimate way of taking care of complex CD fistulae that are making a patient’s life miserable and are not responsive to therapy is with diversion and/or proctectomy. I really reserve this for those patients who just do not respond to medical management. Thankfully those are few and far between.”

Temporary fecal diversion occurs in about 50% of patients with severe fistulizing disease, he said, with permanent ostomy in about 30%, according to medical literature. Diversion succeeds in controlling disease in approximately 64% of patients who undergo this procedure; however, the successful restoration of bowel continuity in such cases can be as low as 17%.

“While our understanding of CD has improved, we still don’t know some of the basic answers about how to best intervene and completely disrupt the inflammatory cascade,” Dr Snyder said.

New medical therapeutics and stem cells are bright lights on the horizon for those who treat this complication of Crohn disease.

“In my practice and into the future, a multidisciplinary approach continues to be critical to manage these complex patients,” he said.

—Rebecca Mashaw

Reference:
Snyder, M. Fistulizing Crohn’s disease. Presented at: Advances in Inflammatory Bowel Diseases. August 27, 2022. Virtual.