DAY 1: Navigating Complications of Crohn’s Disease (CD)

In an afternoon session, 3 presenters described their approaches to the diagnosis and treatment of complicated CD, including perianal fistulas, fibrostenotic disease, and post-operative recurrence.

Dr. David A. Schwartz of Vanderbilt University Medical Center in Nashville, TN, reviewed the management of perianal fistulizing CD. This complication once had a lifetime cumulative incidence of about 25%, which fell to 14% among patients treated early in the anti-TNF era, underscoring the value of early diagnosis and treatment. Even with advanced therapies, long-term fistula healing is achieved in only about one-third of patients. Optimal initial management begins with drainage of all abscesses followed by a complete workup. Missed fistulas at examination under anesthesia (EUA) remain a pitfall, and combining MRI with endoscopic ultrasound (EUS) or EUA has been shown to increase diagnostic accuracy to nearly 100%. Classification serves both to align language with the surgeon and to stratify risk; for example, simple disease is distinguished from complex disease based on sphincter involvement or connection to adjacent organs. Dr. Schwartz advocated a patient-focused perianal classification that aligns with patient goals, including the choice to pursue aggressive versus conservative treatment, achieve cure versus symptom management, and prioritize quality-of-life endpoints. Setons are used to prevent premature closure of fistula openings and thereby reduce recurrence and sphincter damage. Antibiotics are widely used despite limited prospective data, with good outcomes reported for adalimumab combined with ciprofloxacin, and antibiotics should be continued until the seton is removed. Anti-TNF agents have transformed care since the first infliximab study in 1999. All available anti-TNF agents now have data in fistulizing CD, with about 70% of patients improving, though higher trough levels are required than for luminal disease. Post hoc, retrospective, and case-based data also support the use of ustekinumab, vedolizumab, JAK inhibitors such as filgotinib, with benefits for both remission and drainage. Stem cell therapy is unlikely to reach the US market within the next decade: a European trial showed promising results and led to EMA approval, but the ADMIRE 2 trial in the United States was negative, likely because fistula curettage alone drives much of the benefit. The STOMP 2 trial reported positive results with stem cells placed into the fistula, however. Outcomes may be improved by using imaging, particularly EUS, to guide seton placement and the timing of therapy. Resolution of inflammation on imaging should be regarded as the perianal equivalent of mucosal healing in luminal disease, as patients with radiographic healing are less likely to experience recurrence, and those achieving deep remission on MRI have better outcomes and fewer hospital days. A practical pathway begins with initial imaging, followed by surgical drainage and seton placement, then medical therapy with antibiotics plus a JAK or IL-23 inhibitor, with reimaging at 12 to 24 weeks guided by patient-reported drainage volume and color. Depending on imaging findings, the seton may be removed and the opening closed, or medical therapy optimized, possibly with reintroduction of an antibiotic.

Dr. Raymond K. Cross, of the Melissa L. Posner Institute for Digestive Health & Liver Disease at Mercy Medical Center in Baltimore, MD, reviewed current and emerging management of fibrostenotic CD. Stricturing and penetrating complications occur in nearly all patients with ileal disease and in about a third of those with colonic disease, although the risk of surgery has fallen from 46% to 26% since the introduction of anti-TNFs. Recognition is often delayed because 20% to 40% of patients are asymptomatic and symptoms can be misattributed to irritable bowel syndrome. Dr. Cross described using a dietary stress test that asks patients how they feel after eating a sandwich or an apple, a salad, and a steak or a burger to uncover tolerance limits. Stricture severity correlates poorly with symptoms, with proximal strictures more symptomatic and colonic strictures often mild or silent. A stricture is defined endoscopically by inability to pass the scope and on cross-sectional imaging by wall thickening relative to adjacent bowel, luminal narrowing, and prestenotic dilation, though short strictures can be difficult to identify. The accuracy of intestinal ultrasound, CT, and MRI varies by stricture location. Strictures were historically dichotomized as inflammatory, defined by response to prednisone and treated medically, or fibrotic and requiring surgery, but are now understood to be a mixture, raising the question of what proportion of the stricture is reversible. Prestenotic dilation, elevated CRP, B3 phenotype, NOD2 mutation, and prior failure of medical therapy predict the need for surgery. Medically, 5-ASAs and immunomodulators are not recommended, corticosteroids serve as a bridge to another agent, and anti-TNF therapy or combination therapy are preferred, with IL-23 inhibitors and upadacitinib as additional options. In the CREOLE study of adalimumab, half of patients had failed by 5 years, but patients with shorter disease duration, shorter strictures, and no prestenotic dilation or fistula did substantially better, with success rates approaching 90% compared with 6% at the opposite end of the risk spectrum. In STRIDENT, 80% of patients on optimized therapy achieved symptomatic improvement at 12 months versus 64% without. Endoscopic balloon dilation is effective for short strictures, with a systematic review reporting 90% technical success, symptomatic improvement in 80%, and complications in 8%, although most patients experience recurrent symptoms, require redilation, or proceed to surgery within 5 years. Longer strictures carry greater surgical risk. Outcomes follow a “rule of thirds” at 5 years: one-third need a single dilation, one-third require redilation, and one-third proceed to surgery. Dilating to 15-18 mm, which may be done across multiple sessions, increases success. Emerging options include paclitaxel-coated balloons, which lower reintervention rates through a local antifibrotic effect, and AGMB-129, an oral, gut-restricted small molecule inhibitor of activin receptor-like kinase 5 (ALK5) that blocks profibrotic TGF-β signaling and, because of extensive first-pass metabolism, lacks systemic effects. A high dose of AGMB-129 produced significant improvement in patient-reported symptoms as well as in narrowing and mucosal ulceration. Dr. Cross emphasized that resection should not be seen as a failure of medical management but as a tool to help patients feel better, and that top-down early combination therapy begun within weeks to months of diagnosis reduces surgical risk and may prevent strictures from forming. 

Dr. Jana G. Al Hashash of Mayo Clinic in Jacksonville, FL, reviewed management of postoperative CD. Despite advanced therapies, surgery remains common, particularly for medically refractory disease or complications such as stricture, abscess, penetrating or fistulizing disease, and malignancy, with ileocecal resection and anastomosis the most frequent operation. Recurrence follows a predictable sequence: histologic recurrence within the first week, endoscopic recurrence reaching 90% by 1 year in high-risk patients, then radiologic damage and finally clinical symptoms. Patients may be asymptomatic initially, but half will require repeat surgery within 5 years if endoscopic recurrence remains unaddressed. Endoscopy is the gold standard for assessment, using the Rutgeerts score, or the modified Rutgeerts score when ulceration is confined to the anastomosis. Scores correlate with the risk of surgical and symptomatic recurrence, although the threshold for initiating therapy can be difficult to define. Deciding whether to watch and wait or treat depends on risk factors spanning patient, disease (age of onset, extent, behavior, prior therapies), genetic, surgical, serologic, and ‘omics domains. High-risk features include young age at surgery, active smoking, two or more prior resections, penetrating disease, perianal disease, and no prior medical therapy, while low-risk features include older age, nonsmoking status, surgery for a short stricture, and shorter disease duration. For prophylaxis, anti-TNF therapy has made a remarkable difference, with infliximab achieving endoscopic remission in 91% of patients. Data on other biologics are more heterogeneous, although the REPREVIO study showed reduced recurrence with vedolizumab at week 26, and a recently published population-based retrospective cohort study of 18-month recurrence found that any biologic outperformed no biologic, with ustekinumab and vedolizumab effective and anti-TNF therapy reducing recurrence to 10%. Reusing a previously failed biologic can be effective but must be individualized according to why it failed, whether because of refractory disease or advanced disease stage. A recent study in resected, biologic-experienced patients found comparable benefit from reusing a prior biologic or starting a new one. A small retrospective chart review supported low-dose metronidazole for 3 months postoperatively, though side effects are common and the benefit disappears once the drug is stopped. Regarding monitoring, the POCER trial risk-stratified patients, treated those at high risk, and randomized participants to endoscopy at 6 or 18 months; better outcomes were achieved among those treated and scoped at 6 months, supporting close surveillance. Guidelines recommend starting anti-TNF or vedolizumab within 2 to 4 weeks of surgery in high-risk patients, followed by ultrasound at 3 months, colonoscopy at 6 to 12 months, and subsequent follow-up guided by the Rutgeerts score; low-risk patients can be observed, with initial assessment at 3 months, colonoscopy at 6 to 12 months, and follow-up every 1 to 3 years. Surgeons are also modifying operative techniques to reduce the risk of recurrence.