Uni Wong, MD, on Complicated Crohn Disease in 2022

Crohn disease can present challenging complications, including stricturing, penetrating disease, and perianal fistulae, which require different treatment approaches, said Uni Wong, MD, who spoke at the Advances in Inflammatory Bowel Diseases regional meeting in Raleigh, North Carolina, on April 2.

Dr Wong is an assistant professor of medicine at the University of Maryland School of Medicine in Baltimore.

She explained that certain types of complications are more often seen with different presentations of Crohn disease. For example, colonic Crohn disease has a higher rate of both penetrating and stricturing disease, while ileal Crohn more frequently involves penetrating disease than stricturing.

Strictures can be either inflammatory or fibrotic, she noted. Inflammatory strictures may present with mucosal hyperenhancement, mesenteric fat stranding, or mesenteric hypervascularity, or “comb sign”. A thickened wall without signs of active inflammation and “dilation of the proximal intestine strongly suggests a fixed, chronic obstruction,” she stated.

Stricturing Crohn disease can respond to medical therapy, Dr Wong noted. A single-center retrospective study of 51 patients—96% with small bowel intestinal stenosis—reviewed the efficacy of adalimumab (used with 63% of patients), infliximab (37%), and combination therapy (18%). At a median follow-up 16 months, 20 patients, or 39.2%, required surgery to treat their strictures. The primary risk factors for surgery were found to be colonic involvement, prestenotic dilatation, and nonperianal fistula.

Among the CREOLE study of adalimumab among 97 patients with symptomatic Crohn disease stricture, 64% achieved success at week 2, Dr Wong added.

Perhaps most important, she stated, is the fact that early treatment of Crohn disease can prevent stricturing disease. Dr Wong referenced a study by Safroneeva et al, in which patients treated early with anti-tumor necrosis factor (TNF) with or without immunomodulators had significant lower risk of needing surgery than patients who received later treatment. Patients who received only immunomodulators early in the course of disease also had increased risk of needing surgical intervention for stricturing disease.

Among penetrating complications of Crohn disease, the preoperative management of intra-abdominal abscess can decrease morbidity, Dr Wong explained. Nutritional support can prepare patients for better outcomes with the implementation of total parenteral nutrition (TPN) or enteral nutrition using an elemental diet. One retrospective study showed that of 78 patients who received this nutritional support prior to surgery for penetrating Crohn disease, 7.7% required a diverting stoma and 5% experienced major postoperative complications.

In addition to nutrition, Dr Wong noted that antibiotic coverage, drainage, and reduction or elimination of corticosteroids also help reduce subsequent morbidity among patients with abdominal abscess. These patients also require thromboembolic prophylaxis, short-term cessation of immunosuppressants and biologics, and should be offered smoking cessation support.

She explored the pros and cons of early surgery for abscesses vs medical therapy, noting that research indicates that abscesses related to strictures and/or fistulae are best treated surgically, particularly if any strictures are fibrotic. Dr Wong reported that in one study, 27 patients with intra-abdominal abscess with associated fistulas needed surgery within 30 days, despite drainage.

Beginning medical therapy after abscess drainage reduced the risk of recurrent abscesses, Dr Wong noted. Among 55 patients who underwent percutaneous drainage and 40 who underwent surgery in a Mayo Clinic study, the 5-year cumulative probability of abscess recurrence was 31.2% in the nonsurgical group vs 20.3% in the surgical group.

The predictors of abscess recurrence included perianal disease and active ileal disease.

Antibiotics, including ciprofloxacin and metronidazole, can lead to improvement in symptoms such as drainage, but rarely lead to complete healing, she noted. Relapses are common once antibiotics are discontinued.

Infliximab, vedolizumab, and ustekinumab have all been examined for their efficacy in treating perianal Crohn disease, Dr Wong stated. A study of 94 patients, of whom 85 had perianal fistulae, demonstrated that 68% of those treated with infliximab experienced ≥50% reduction in draining fistulas vs 26% on placebo. Another study by by Sands et al revealed that 46% of patients on infliximab had fistula response vs 23% on placebo; of these patients, 36% of those receiving infliximab showed complete response vs 19% on placebo.

Combination therapy helps to preserve drug efficacy and prevent immunogenicity, Dr Wong stated, and increases fistula closure. “Drug level matters,” she noted, referencing a study that showed patients with fistula healing had higher infliximab levels than those who did not experience such healing, while higher drug levels at induction predicted response.

The GEMINI 2 trial examined the efficacy of vedolizumab among 153 patients with fistulizing disease; 57 of these patients had 1 or more active draining fistulae. At week 52, 33% of patients who received vedolizumab throughout the trial achieved fistula closure, vs 11% of those who began with vedolizumab but were changed to placebo.

Dr Wong noted that the Dutch Initiative on Crohn and Colitis found that 35.7% of patients who received ustekinumab had clinical resolution after 24 weeks, while in the GETAID Study Group of 207 patients “success was achieved in 57 of 148 patients (38.5%) with active perianal CD.” Among 88 patients with setons, 29 (33%) had successful removal.

A multidisciplinary approach is essential in treating perianal Crohn disease, Dr Wong stated. Among patients who received setons followed by infliximab, 100% had response vs 83% who received infliximab alone; 79% of patients on infliximab along experienced recurrence vs 44% of those with setons and infliximab therapy.

Dr Wong reviewed a number of surgical options for perianal Crohn disease, including seton placement; fistulotomy; application of fibrin glue and fistula plugs; ligation of intersphincteric fistula; endorectal advancement flap; diversion/proctectomy; and mesenchymal stem cell therapy

Among patients who receive fecal diversion, about 20% will need proctectomy and the majority will require a permanent stoma, she explained. In a review of 68 fecal diversions without proctectomy, 37% experienced sustained healing; 31% restored continuity; 22% required proctectomy; and 21% had ostomy-free survival.

Stem cell therapy is a very promising new treatment for perianal disease, Dr Wong said. It has been shown to reduce exacerbated inflammation and provide immunomodulatory effects. Stem cells will migrate to sites of active inflammation and tissue injury, where they secrete anti-inflammatory molecules and help “to maintain the local anti-inflammatory environment.” She added that stem cells derived from adipose tissue rather than bone marrow replicate faster and proliferate longer in culture.

A retrospective chart review of patients who underwent stem cell therapy for perianal disease in the ADMIRE-CD trial showed that at 52 weeks, 67.4% who received the stem cell therapy darvadstrocel remained in clinical remission, compared to 52.2% of the control group. At 156 weeks, 53.5% of the stem cell group remained in remission, vs 45.7% of the control group.

In summarizing her key points, Dr Wong said, “Stricture is a common complication of Crohn’s disease; early treatment can prevent stricture. Penetrating Crohn disease with associated stricture requires resection. Perianal Crohn disease requires a multidisciplinary approach which may include the drainage of fistulae with seton placement, medical therapy, stem cell therapy, and possible fecal diversion with or without proctectomy.”

--Rebecca Mashaw

Wong, U. Complicated Crohn’s disease in 2022. Presented at: Advances in Inflammatory Bowel Diseases. Raleigh, North Carolina. April 2, 2022.