At Vanderbilt University Medical Center, physicians are moving the needle away from reactive and resigned thinking and toward smart, strategic management of Crohn’s disease and other inflammatory bowel diseases (IBDs). Through teaming up in the clinic and in the hospital, and rethinking assumptions about medications, they are working to avoid or forestall surgeries, including intestinal resection. Vanderbilt is also participating in trials of new drugs that may improve patient outcomes.
“No day is simple,” says Robin Ligler Dalal, M.D., a gastroenterologist at Vanderbilt’s Inflammatory Bowel Disease Clinic. “These are complex conditions that require us to look at how we collaborate with our surgical colleagues, how we time and dose medications around surgery, and how we approach the diseases early on to optimize long-term management.”
Biologics: Welcome, But Not a Panacea
“Overall, the shift from corticosteroids to biologics and more immunosuppressants has improved management of IBD and short bowel syndrome,” said Dawn Wiese Adams, M.D., a gastroenterologist and director of the Celiac Disease Clinic at Vanderbilt. “We are doing less surgery on these patients thanks to these drugs, and they are reducing the need for total parenteral nutrition or IV support for patients with intestinal failure.”
Yet she and Dalal agree that biologics are not a panacea. While colectomy rates for ulcerative colitis are on a sharp decline since the advent of biologic therapy, no such trend has been seen with Crohn’s disease.
“These are complex conditions that require us to look at how we collaborate with our surgical colleagues, how we time and dose medications around surgery, and how we approach the diseases early on.”
There is also uncertainly around perioperative use. “Everyone is excited about biologics, but how are they working for the patient who is presurgical? We are just beginning to examine their role in avoiding surgical site and deeper infections, for example,” Dalal said.
Nuanced Perioperative Decisions
In some studies, perioperative use of anti-TNF agents and other biologics have been associated with more complications in Crohn’s and ulcerative colitis patients. However, these drugs present no increased risk to patients undergoing colectomy or total proctocolectomy with end iliostomy. “We are often using vedolizumab because of its better safety profile and using ustekinumab for safety and low association with perioperative complications compared with other biologics,” Adams said.
New data are also changing decisions on how drugs may affect surgical timing. The 2019 PUCCINI trial that examined anti-TNF therapy and risks of postoperative infection, demonstrated that biologic levels at the time of surgery were not an independent risk factor for surgical site or other infections. Dalal says this was pivotal in reducing complications caused by delayed surgeries.
Vanderbilt is working on collaborations between IBD clinicians and surgeons to apply the evidence, case by case, to develop best treatment plans together. A specific consult service is also launching for IBD inpatients, Dalal says. “We’ll be able to see every IBD patient when they’re in the hospital. Hopefully, we will prevent anyone from falling through the cracks – not getting the follow-up and holistic disease management they need.”
Evaluating Drug Therapy
Additionally, on the perioperative front, Vanderbilt is participating in a clinical trial of TAK-018, a FimH blocker given postoperatively, that may reduce Crohn’s recurrence. “In the current study, our surgeons are using this with select and qualified patients with ileocecal resection,” said Dalal, who is site principal investigator.
In Vanderbilt’s Center for Human Nutrition, Adams is leading Vanderbilt’s participation in a trial of two new drugs – apraglutide and glepaglutide – which are analogs of GLP-2, a gut growth hormone. Adams says the drugs look promising for patients with resected intestines and short bowel syndrome.
“Clinical studies with Gattex®, the recombinant human GLP-2 now in phase 3 trials, demonstrate a significant reduction in parenteral needs in adults with short bowel syndrome, due to the effects of GLP-2 on adaptation and growth of the small intestine,” Adams said.
Designed as an alternative to Gattex, which requires daily injections, newer GLP-2 analogs would require only twice weekly or weekly injections. Adams says this is not only more convenient, but the longer-acting drugs may have higher efficacy and decreased adverse effects.
Treatment Targets Remission
For patients affected by IBD and short bowel syndrome, Vanderbilt practitioners are intent on addressing the nuances of a complex decision-making matrix. “Too often, these illnesses have been treated on an emergent basis. Even after surgery, too many patients in the past have been given some take-home instructions, but little follow-up,” Adams said.
In the IBD Clinic, full remission is the target. “We work toward helping patients feel well, but our real target is to get them into a deep remission, which is when their bowel is healed. Most of the time these two goals go hand in hand,” Dalal said.